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Sample records for chinese vaccine strain

  1. Genomic comparison between attenuated Chinese equine infectious anemia virus vaccine strains and their parental virulent strains.

    PubMed

    Wang, Xuefeng; Wang, Shuai; Lin, Yuezhi; Jiang, Chenggang; Ma, Jian; Zhao, Liping; Lv, Xiaoling; Wang, Fenglong; Shen, Rongxian; Kong, Xiangang; Zhou, Jianhua

    2011-02-01

    A lentiviral vaccine, live attenuated equine infectious anemia virus (EIAV) vaccine, was developed in the 1970s, and this has made tremendous contributions to the control of equine infectious anemia (EIA) in China. Four key virus strains were generated during the attenuation of the EIAV vaccine: the original Liao-Ning strain (EIAV(LN40)), a donkey-adapted virulent strain (EIAV(DV117)), a donkey-leukocyte-attenuated vaccine strain (EIAV(DLV121)), and a fetal donkey dermal cell (FDD)-adapted vaccine strain (EIAV(FDDV13)). In this study, we analyzed the proviral genomes of these four EIAV strains and found a series of consensus substitutions among these strains. These mutations provide useful information for understanding the genetic basis of EIAV attenuation. Our results suggest that multiple mutations in a variety of genes in our attenuated EIAV vaccines not only provide a basis for virulence attenuation and induction of protective immunity but also greatly reduce the risk of reversion to virulence.

  2. Genomic sequence and virulence of clonal isolates of vaccinia virus Tiantan, the Chinese smallpox vaccine strain.

    PubMed

    Zhang, Qicheng; Tian, Meijuan; Feng, Yi; Zhao, Kai; Xu, Jing; Liu, Ying; Shao, Yiming

    2013-01-01

    Despite the worldwide eradication of smallpox in 1979, the potential bioterrorism threat from variola virus and the ongoing use of vaccinia virus (VACV) as a vector for vaccine development argue for continued research on VACV. In China, the VACV Tiantan strain (TT) was used in the smallpox eradication campaign. Its progeny strain is currently being used to develop a human immunodeficiency virus (HIV) vaccine. Here we sequenced the full genomes of five TT clones isolated by plaque purification from the TT (752-1) viral stock. Phylogenetic analysis with other commonly used VACV strains showed that TT (752-1) and its clones clustered and exhibited higher sequence diversity than that found in Dryvax clones. The ∼190 kbp genomes of TT appeared to encode 273 open reading frames (ORFs). ORFs located in the middle of the genome were more conserved than those located at the two termini, where many virulence and immunomodulation associated genes reside. Several patterns of nucleotide changes including point mutations, insertions and deletions were identified. The polymorphisms in seven virulence-associated proteins and six immunomodulation-related proteins were analyzed. We also investigated the neuro- and skin- virulence of TT clones in mice and rabbits, respectively. The TT clones exhibited significantly less virulence than the New York City Board of Health (NYCBH) strain, as evidenced by less extensive weight loss and morbidity in mice as well as produced smaller skin lesions and lower incidence of putrescence in rabbits. The complete genome sequences, ORF annotations, and phenotypic diversity yielded from this study aid our understanding of the Chinese historic TT strain and are useful for HIV vaccine projects employing TT as a vector.

  3. Chinese border disease virus strain JSLS12-01 infects piglets and down-regulates the antibody responses of classical swine fever virus C strain vaccination.

    PubMed

    Mao, Li; Li, Wenliang; Liu, Xia; Hao, Fei; Yang, Leilei; Deng, Jiawu; Zhang, Wenwen; Wei, Jianzhong; Jiang, Jieyuan

    2015-07-31

    During 2012 and 2013, several border disease virus (BDV) strains were identified from Chinese goat and sheep herds. At the same time, pigs from the same areas were found to be seropositive to BDV by ELISA, without showing clinical signs (unpublished data). To examine the susceptibility of pigs to the Chinese BDV strains, BDV isolate JSLS12-01, isolated from naturally infected sheep, was used to infect pigs. Antibody responses, viremia, clinical signs and pathological changes of the infected animals were examined. It confirmed that the current BDV strain could infect the domestic pigs, the animals showed viremia during 4 to 14 days post infection (dpi) and sero-conversion from 14dpi; no clinical and pathological changes were observed. In addition, CSFV maternal antibody did not influence BDV infection. Subsequently, pigs were infected with the BDV isolate and vaccinated with Hog cholera lapinized virus (HCLV) 21 days later to determine the effect of BDV infection on antibody induction of CSFV vaccination. The specific CSFV antibody and neutralizing antibody titers of the BDV infected group remained negative after the primary vaccination. Even after the boost vaccination, they were still significantly lower than those of the uninfected groups (p<0.05). These results indicated that BDV infection could down-regulate the antibody responses of CSFV C-strain vaccination. It should be paid attention that BDV prevalence in pig herds and in live vaccines might hamper the vaccination of CSF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Pigs immunized with Chinese highly pathogenic PRRS virus modified live vaccine are protected from challenge with North American PRRSV strain NADC-20.

    PubMed

    Galliher-Beckley, Amy; Li, Xiangdong; Bates, John T; Madera, Rachel; Waters, Andrew; Nietfeld, Jerome; Henningson, Jamie; He, Dongsheng; Feng, Wenhai; Chen, Ruiai; Shi, Jishu

    2015-07-09

    Modified live virus (MLV) vaccines developed to protect against PRRSV circulating in North America (NA) offer limited protection to highly pathogenic (HP) PRRSV strains that are emerging in Asia. MLV vaccines specific to HP-PRRSV strains commercially available in China provide protection to HP-PRRSV; however, the efficacy of these HP-PRRSV vaccines to current circulating NA PRRS viruses has not been reported. The aim of this study is to investigate whether pigs vaccinated with attenuated Chinese HP-PRRSV vaccine (JXA1-R) are protected from infection by NA PRRSV strain NADC-20. We found that pigs vaccinated with JXA1-R were protected from challenges with HV-PRRSV or NADC-20 as shown by fewer days of clinical fever, reduced lung pathology scores, and lower PRRS virus load in the blood. PRRSV-specific antibodies, as measured by IDEXX ELISA, appeared one week after vaccination and virus neutralizing antibodies were detected four weeks post vaccination. Pigs vaccinated with JXA1-R developed broadly neutralizing antibodies with high titers to NADC-20, JXA1-R, and HV-PRRSV. In addition, we also found that IFN-α and IFN-β occurred at higher levels in the lungs of pigs vaccinated with JXA1-R. Taken together, our studies provide the first evidence that JXA1-R can confer protection in pigs against the heterologous NA PRRSV strain NADC-20. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Rovac is the possible ancestor of the Russian lapinized vaccines LK-VNIVViM and CS strains but not the Chinese strain (C-strain) vaccine against classical swine fever.

    PubMed

    Zhou, Weiguang; Gao, Shandian; Podgórska, Katarzyna; Stadejek, Tomasz; Qiu, Hua-Ji; Yin, Hong; Drew, Trevor; Liu, Lihong

    2014-11-20

    Classical swine fever (CSF), or hog cholera, is a highly contagious disease that emerged in the first half of the nineteenth century. To fight against the disease and protect pigs, different vaccines were developed, including early generation of lapinized Rovac strain and the later development of the “Chinese” strain (C-strain). However, details of the development of these vaccines are lost in history. In order to investigate the phylogenetic relationship between the Rovac and other lapinized vaccines, this study determined the genome sequence of the Rovac, which comprised 12,304 nucleotides, notably with the 3′untranslated region (3′UTR) containing a 13-nucleotide insertion. The near-complete genome of Russian vaccine strain LK-VNIVViM was determined by next-generation sequencing on Illumina MiSeq platform. Whole genome phylogenetic analysis revealed a closer relationship of the Rovac strain with the Russian LK-VNIVViM, CS strain and its derivative RUCSFPLUM (genotype 1.2), rather than with the C-strain (genotype 1.1). In addition, it demonstrated an ancestry role of the LK-VNIVViM in relation to the CS strain and RUCSFPLUM. The study suggested that the Rovac vaccine is the possible ancestor of the Russian vaccine strains but not the C-strain vaccine.

  6. Protection of Chinese painted quails (Coturnix chinensis) against a highly pathogenic H5N1 avian influenza virus strain after vaccination.

    PubMed

    Sarkadi, Julia; Jankovics, Mate; Kis, Zoltan; Skare, Jozsef; Fodor, Kinga; Gonczol, Eva; Visontai, Ildiko; Vajo, Zoltan; Jankovics, Istvan

    2013-12-01

    Chinese painted quails immunized with a single dose (6 μg HA) of inactivated H5N1 (clade 1) influenza vaccine NIBRG-14 and challenged with 100 LD50 of the heterologous A/Swan/Nagybaracska/01/06(H5N1) (clade 2.2) strain were protected, whereas unvaccinated quails died after challenge. No viral antigens or RNA were detected in cloacal swabs from immunized animals. Sera obtained post-immunization gave low titres in serological assays against the vaccine and the challenge viruses. Our results demonstrate the protective efficacy of the NIBRG-14 strain against the challenge virus and the usefulness of these small birds in protection studies of influenza vaccines.

  7. Adaptation of a Chinese ferret badger strain of rabies virus to high-titered growth in BHK-21 cells for canine vaccine development.

    PubMed

    Liu, Ye; Zhang, Shoufeng; Zhang, Fei; Hu, Rongliang

    2012-12-01

    Rabies virus strain JX08-45CC was derived from a Chinese isolate (JX08-45) by serial passage in the BHK-21 cell line, reaching a titer of 10(8) TCID(50)/mL. JX08-45CC produced rabies in adult mice but was nonpathogenic in dogs after intramuscular injection. A comparison of the entire genomes of JX08-45 and JX08-45CC led to the identification of 17 nucleotide substitutions, resulting in seven amino acid changes in the mature G and L proteins. The immunogenicity of β-propiolactone-inactivated JX08-45CC was similar to the immunogenicity of the live vaccine strains widely used in China. The inactivated vaccine induced antibody responses for more than 6 months and provided full protection from an intramuscular challenge in dogs. JX08-45CC has excellent potential for development as an inactivated vaccine for dogs in China.

  8. Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies.

    PubMed

    Han, Xiue; Zhang, Ping; Yu, Wei; Xiang, Wenhua; Li, Xiaodong

    2016-12-01

    The Chinese EIAV vaccine is an attenuated live virus vaccine obtained by serial passage of a virulent horse isolate (EIAVL) in donkeys (EIAVD) and, subsequently, in donkey cells in vitro. In this study, we compare the env gene of the original horse virulent virus (EIAVL) with attenuated strains serially passaged in donkey MDM (EIAVDLV) and donkey dermal cells (EIAVFDDV). Genetic comparisons among parental and attenuated strains found that vaccine strains contained amino acid substitutions/deletions in gp90 that resulted in a loss of three potential N-linked glycosylation sites, designated g5, g9, and g10. To investigate the biological significance of these changes, reverse-mutated viruses were constructed in the backbone of the EIAVFDDV infectious molecular clone (pLGFD3). The resulting virus stocks were characterized for replication efficiency in donkey dermal cells and donkey MDM, and were tested for sensitivity to neutralization using sera from two ponies experimentally infected with EIAVFDDV. Results clearly show that these mutations generated by site-directed mutagenesis resulted in cloned viruses with enhanced resistance to serum neutralizing antibodies that were also able to recognize parental viruses. This study indicates that these mutations played an important role in the attenuation of the EIAV vaccine strains.

  9. Protection tests in pigs vaccinated with the lapinized Chinese strain of hog cholera virus (HCV) previously adapted in a minipig kidney (MPK) cell line, to challenge infection with virulent HCV.

    PubMed

    Gualandi, G L; Ferrari, M; Cardeti, G; Boldini, M; Buonavoglia, C

    1991-07-01

    Pigs which had been vaccinated with the Lapinized Chinese strain of Hog Cholera Virus previously adapted in a minipig cell line cultures (MPK-LC-HCV), resultet to be protected when they were subjected to challenge infection with virulent Hog Cholera Virus (HCV) 6 or 11 months later. The challenge virus was never isolated from any of the vaccinated pigs. The MPK-LC-HCV vaccine induced a significant rise of the antibody titer to the HCV in pigs kept under field conditions.

  10. Chinese vaccine products go global: vaccine development and quality control.

    PubMed

    Xu, Miao; Liang, Zhenglun; Xu, Yinghua; Wang, Junzhi

    2015-05-01

    Through the continuous efforts of several generations, China has become one of the few countries in the world that is capable of independently addressing all the requirements by the Expanded Program on Immunization. Regulatory science is applied to continuously improve the vaccine regulatory system. Passing the prequalification by WHO has allowed Chinese vaccine products to go global. Chinese vaccine products not only secure disease prevention and control domestically but also serve the needs for international public health. This article describes the history of Chinese vaccine development, the current situation of Chinese vaccine industry and its contribution to the prevention and control of infectious diseases. We also share our experience of national quality control and vaccine regulation during the past decades. China's experience in vaccine development and quality control can benefit other countries and regions worldwide, including the developing countries.

  11. Genetic characterization of measles vaccine strains.

    PubMed

    Bankamp, Bettina; Takeda, Makoto; Zhang, Yan; Xu, Wenbo; Rota, Paul A

    2011-07-01

    The complete genomic sequences of 9 measles vaccine strains were compared with the sequence of the Edmonston wild-type virus. AIK-C, Moraten, Rubeovax, Schwarz, and Zagreb are vaccine strains of the Edmonston lineage, whereas CAM-70, Changchun-47, Leningrad-4 and Shanghai-191 were derived from 4 different wild-type isolates. Nucleotide substitutions were found in the noncoding regions of the genomes as well as in all coding regions, leading to deduced amino acid substitutions in all 8 viral proteins. Although the precise mechanisms involved in the attenuation of individual measles vaccines remain to be elucidated, in vitro assays of viral protein functions and recombinant viruses with defined genetic modifications have been used to characterize the differences between vaccine and wild-type strains. Although almost every protein contributes to an attenuated phenotype, substitutions affecting host cell tropism, virus assembly, and the ability to inhibit cellular antiviral defense mechanisms play an especially important role in attenuation.

  12. Introduction of an update system for vaccine strains of veterinary influenza vaccines in Japan.

    PubMed

    Gamoh, Koichiro; Nakamura, Shigeyuki

    2015-03-01

    The basic countermeasures used to control highly pathogenic avian influenza (HPAI) are early detection procedures and the culling of affected chickens. However, if successive HPAI outbreaks occur, the vaccination may be an option for controlling HPAI. Therefore, avian influenza (AI) vaccines are stocked by the Japanese government. By contrast, equine influenza (EI) vaccine is an effective tool for preventing or controlling EI. Because antigenic drifts affect the efficacy of AI and EI vaccines, the vaccine strains should be updated rapidly. However, the development and registration of veterinary vaccines usually takes several years. In response to this issue, the Ministry of Agriculture, Forestry, and Fisheries (MAFF) established a system that allows AI and EI vaccine strains to be updated rapidly. National Veterinary Assay Laboratory, MAFF, established a vaccine strains selection committee for veterinary influenza vaccine. The main agendas involve determining whether the current vaccine strains need to be updated and selecting the most appropriate vaccine strains. The committee concluded that A/duck/Hokkaido/Vac-3/2007(H5N1) was added to the strains of stockpiled AI vaccines and that the EI vaccine strains did not need to be changed, but that the clade 2 viruses of the Florida sub-lineage strain, A/equine/Yokohama/aq13/2010(H3N8) was added to the EI vaccine strain.

  13. Development of a combined canine distemper virus specific RT-PCR protocol for the differentiation of infected and vaccinated animals (DIVA) and genetic characterization of the hemagglutinin gene of seven Chinese strains demonstrated in dogs.

    PubMed

    Yi, Li; Cheng, Shipeng; Xu, Hongli; Wang, Jianke; Cheng, Yuening; Yang, Shen; Luo, Bin

    2012-01-01

    A combined reverse-transcription polymerase chain reaction (RT-PCR) method was developed for the detection and differentiation of wild-type and vaccine strains of the canine distemper virus (CDV). A pair of primers (P1/P2) was used to detect both CDV wild-type strains and vaccines. Another pair (P3/P4) was used to detect only CDV wild-type strains. A 335bp fragment was amplified from the genomic RNA of the vaccine and wild-type strains. A 555bp fragment was amplified specifically from the genomic RNA of the wild-type strains. No amplification was achieved for the uninfected cells, cells infected with canine parvovirus, canine coronavirus, or canine adenovirus. The combined RT-PCR method detected effectively and differentiated the CDV wild-type and vaccine strains by two separate RT-PCRs. The method can be used for clinical detection and epidemiological surveillance. The phylogenetic analysis of the hemagglutinin gene of the local wild-type CDV strains revealed that the seven local isolates all belonged to the Asia-1 lineage, and were clustered closely with one another at the same location. These results suggested that the CDV genotype Asia-1 is circulating currently in domestic dogs in China.

  14. A pilot study on an attenuated Chinese EIAV vaccine inducing broadly neutralizing antibodies.

    PubMed

    Meng, Qinglai; Lin, Yuezhi; Ma, Jian; Ma, Yan; Zhao, Liping; Li, Shenwei; Liang, Hua; Zhou, Jianhua; Shen, Rongxian; Zhang, Xiaoyan; Shao, Yiming

    2011-08-01

    The attenuated Chinese equine infectious anemia virus (EIAV) vaccine has successfully protected millions of equine animals from EIA disease in China. In this pilot study, to determine whether this attenuated vaccine can induce broadly neutralizing antibodies, we immunized four horses with the attenuated Chinese vaccine strain EIAVFDDV and then observed the evolution of neutralizing antibodies against different EIAV strains. During the vaccination phase, all vaccinees rapidly developed high levels of neutralizing antibodies against the homologous vaccine strain (pLGFD3V), and 3 out of 4 horses showed a gradual increase in serum neutralizing activity against two relatively heterologous virulent variants of the challenge strain (pLGFD3Mu12V and DLV34). After challenge, the three horses that had developed high levels of neutralizing antibodies against pLGFD3Mu12V and DLV34 did not show signs of infection, which was demonstrated by immune suppression, while the one horse producing serum that could only neutralize pLGFD3V developed a febrile episode during the 8-month observation period. To assess whether the broadly neutralizing activity is associated with immune protection, sera drawn on the day of challenge from these four vaccinees and an additional four EIAVFDDV-vaccinated horses were analyzed for neutralizing antibodies against pLGFD3V, pLGFD3Mu12V and DLV34. Although there was no significant correlation between protection from infection and serum neutralizing activity against any of these three viral strains, protection from infection was observed to correlate better with serum neutralizing activity against the two heterologous virulent strains than against the homologous vaccine strain. These data indicate that EIAVFDDV induced broadly neutralizing antibodies, which might confer enhanced protection of vaccinees from infection by the challenge virus.

  15. Candidate cytomegalovirus strain for human vaccination.

    PubMed Central

    Plotkin, S A; Furukawa, T; Zygraich, N; Huygelen, C

    1975-01-01

    A strain of human cytomegalovirus called Towne was isolated in WI-38 human fibrolast cell cultures from the urine of an infected infant. It was then passaged 125 times in WI-38, including three clonings, and a pool was prepared in the same cell substrate for use as a potential live attenuated vaccine. The Towne virus has a broad antigenicity and cross-reacts with the AD-169 strain. Several markers of the Towne virus were found which differentiated it from fresh isolates. One of these was resistance of the former to trypsin. The Towne virus was tested for freedom from oncogenicity or other harmful effects in preparation for tests in humans. PMID:170203

  16. A generic real-time TaqMan assay for specific detection of lapinized Chinese vaccines against classical swine fever.

    PubMed

    Liu, Lihong; Xia, Hongyan; Everett, Helen; Sosan, Olubukola; Crooke, Helen; Meindl-Böhmer, Alexandra; Qiu, Hua-Ji; Moennig, Volker; Belák, Sándor; Widén, Frederik

    2011-08-01

    Classical swine fever (CSF) is a highly contagious disease, causing severe economic losses in the pig industry worldwide. Vaccination of pigs with lapinized Chinese vaccines is still practised in some regions of the world, where the virus is enzootic, in order to prevent and control the disease. However, a single real-time assay that can detect all lapinized Chinese vaccines used widely, namely, Lapinized Philippines Coronel (LPC), Hog Cholera Lapinized virus (HCLV) and the Riems C-strain is still lacking. This study describes a real-time RT-PCR assay, targeting the N(pro) gene region, for specific detection of these lapinized vaccine strains. The assay is highly sensitive, with a detection limit of 10 genome copies per reaction for HCLV and Riems C-strain and highly specific, as more than 100 strains of wild type CSFV representing all major genotypes were not detected. The assay is also highly repeatable: the coefficient of variation of Ct values in three runs was 2.77% for the detection of 10 copies of the vaccine viral RNA. This study provides a potentially useful tool for specific detection of the lapinized Chinese vaccines, HCLV and C-strain, and the differentiation of these vaccines from wild type CSFV.

  17. Frequency of Adverse Events after Vaccination with Different Vaccinia Strains

    PubMed Central

    Kretzschmar, Mirjam; Wallinga, Jacco; Teunis, Peter; Xing, Shuqin; Mikolajczyk, Rafael

    2006-01-01

    Background Large quantities of smallpox vaccine have been stockpiled to protect entire nations against a possible reintroduction of smallpox. Planning for an appropriate use of these stockpiled vaccines in response to a smallpox outbreak requires a rational assessment of the risks of vaccination-related adverse events, compared to the risk of contracting an infection. Although considerable effort has been made to understand the dynamics of smallpox transmission in modern societies, little attention has been paid to estimating the frequency of adverse events due to smallpox vaccination. Studies exploring the consequences of smallpox vaccination strategies have commonly used a frequency of approximately one death per million vaccinations, which is based on a study of vaccination with the New York City Board of Health (NYCBH) strain of vaccinia virus. However, a multitude of historical studies of smallpox vaccination with other vaccinia strains suggest that there are strain-related differences in the frequency of adverse events after vaccination. Because many countries have stockpiled vaccine based on the Lister strain of vaccinia virus, a quantitative evaluation of the adverse effects of such vaccines is essential for emergency response planning. We conducted a systematic review and statistical analysis of historical data concerning vaccination against smallpox with different strains of vaccinia virus. Methods and Findings We analyzed historical vaccination data extracted from the literature. We extracted data on the frequency of postvaccinal encephalitis and death with respect to vaccinia strain and age of vaccinees. Using a hierarchical Bayesian approach for meta-analysis, we estimated the expected frequencies of postvaccinal encephalitis and death with respect to age at vaccination for smallpox vaccines based on the NYCBH and Lister vaccinia strains. We found large heterogeneity between findings from different studies and a time-period effect that showed

  18. Characterization of Russian rabies virus vaccine strain RV-97.

    PubMed

    Metlin, A; Paulin, L; Suomalainen, S; Neuvonen, E; Rybakov, S; Mikhalishin, V; Huovilainen, A

    2008-03-01

    The RV-97 rabies virus vaccine strain is widely used in Russia as a component of the live attenuated oral anti-rabies vaccine "Sinrab". This vaccine has also been used in some other countries, such as Kazakhstan, Belarus, and Ukraine. Entire genome sequencing is an effective tool for studying the genetic properties of virus strains. In this study, a simple technique for obtaining the entire genome sequence of the rabies virus was used. The entire genome sequence and the deduced amino acid sequences of the major viral proteins were compared with those of other rabies vaccine virus strains. The RV-97 strain forms a separate phylogenetic branch and seems to be phylogenetically more related to the group of Japanese vaccine strains. It also contains several unique amino acid changes in known immunodominant sites of G and P proteins.

  19. Influenza virus surveillance, vaccine strain selection, and manufacture.

    PubMed

    Stöhr, Klaus; Bucher, Doris; Colgate, Tony; Wood, John

    2012-01-01

    As outlined in other chapters, the influenza virus, existing laboratory diagnostic abilities, and disease epidemiology have several peculiarities that impact on the timing and processes for the annual production of influenza vaccines. The chapter provides an overview on the key biological and other factors that influence vaccine production. They are the reason for an "annual circle race" beginning with global influenza surveillance during the influenza season in a given year to the eventual supply of vaccines 12 months later in time before the next seasonal outbreak and so on. As influenza vaccines are needed for the Northern and Southern Hemisphere outbreaks in fall and spring, respectively, global surveillance and vaccine production has become a year round business. Its highlights are the WHO recommendations on vaccine strains in February and September and the eventual delivery of vaccine doses in time before the coming influenza season. In between continues vaccine strain and epidemiological surveillance, preparation of new high growth reassortments, vaccine seed strain preparation and development of standardizing reagents, vaccine bulk production, fill-finishing and vaccine release, and in some regions, clinical trials for regulatory approval.

  20. Rotavirus vaccine strain transmission by vaccinated infants in the foster home.

    PubMed

    Miura, Hiroki; Kawamura, Yoshiki; Sugata, Ken; Koshiyama, Nozomi; Yoshikawa, Akiko; Komoto, Satoshi; Taniguchi, Koki; Ihira, Masaru; Yoshikawa, Tetsushi

    2017-01-01

    Previous studies have demonstrated the transmission of rotavirus vaccine strains from vaccinated children to nonvaccinated siblings. We sought to fully elucidate the safety of rotavirus (RV) vaccination in closed contact circumstance, such as the foster home for future assessment of the vaccine safety in an neonatal intensive care unit. Stool samples were collected from 4 RV vaccinated (160 samples) and 23 unvaccinated (766 samples) infants. RV viral RNA loads were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). RV vaccine strain RNA was persistently detected in stool samples collected from the four vaccine recipients and one unvaccinated infant, but not in the stool samples collected from the 22 other unvaccinated infants. The unvaccinated infant who tested positive for the RV vaccine strain was vaccinated prior to enrollment in this study. The quantitative real-time RT-PCR data revealed a peak viral RNA load 1 week after vaccination followed by a gradual decrease. The current study suggests that RV vaccination may be safe in a close contact environment because there was limited transmission from RV vaccinated to unvaccinated infants. J. Med. Virol. 89:79-84, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Transcriptome analysis of human immune responses following Live Vaccine Strain (LVS) Francisella Tularensis vaccination

    PubMed Central

    Fuller, Claudette L.; Brittingham, Katherine C.; Porter, Mark W.; Hepburn, Matthew J.; Petitt, Patricia L.; Pittman, Phillip R.; Bavari, Sina

    2007-01-01

    The live vaccine strain (LVS) of Francisella tularensis is the only vaccine against tularemia available for humans, yet its mechanism of protection remains unclear. We probed human immunological responses to LVS vaccination with transcriptome analysis using PBMC samples from volunteers at timepoints pre- and post-vaccination. Gene modulation was highly uniform across all time points, implying commonality of vaccine responses. Principal components analysis revealed three highly distinct principal groupings: pre-vaccination (−144 h), early (+18 and +48 h), and late post-vaccination (+192 and +336 h). The most significant changes in gene expression occurred at early post-vaccination timepoints (≤48 h), specifically in the induction of pro-inflammatory- and innate immunity-related genes. Evidence supporting modulation of innate effector function, specifically antigen processing and presentation by dendritic cells, was especially apparent. Our data indicate that the LVS strain of F. tularensis invokes a strong early response upon vaccination. This pattern of gene regulation may provide insightful information regarding both vaccine efficacy and immunopathogenesis that may provide insight into infection with virulent strains of F. tularensis. Additionally, we obtained valuable information that should prove useful in evaluation of vaccine lots as well as efficacy testing of new anti- F. tularensis vaccines. PMID:17349694

  2. Proteomic analysis of Mycoplasma gallisepticum vaccine strain F

    USDA-ARS?s Scientific Manuscript database

    The persistence and displacement abilities of the Mycoplasma gallisepticum vaccine strain F (F-strain) are well documented. Understanding the mechanism(s) of colonization and persistence of F-strain will aid in the current intervention strategies to diagnose and control MG infections in poultry. In ...

  3. Trials with a live attenuated rubella virus vaccine, Cendehill strain

    PubMed Central

    Grant, L.; Belle, E. A.; Provan, G.; King, S. D.; Sigel, M. M.

    1970-01-01

    This report summarizes closed, family, and open studies conducted sequentially over a 10 month period with the Cendehill rubella virus vaccine in more than 16,000 children and adolescents. This strain of rubella was attenuated by serial propagation on primary rabbit kidney cell cultures. Inoculation of the Cendehill vaccine produced seroconversion in 97% of the 3589 susceptible (seronegative) vaccinated persons. There was no spread of the virus to susceptible controls living in close contact with those vaccinated. The vaccine was well tolerated. No arthritis or arthralgia occurred in 860 female subjects 13-18 years of age who were included in the study. The Cendehill vaccine would appear to meet the requirements of an acceptable vaccine. PMID:5272349

  4. Symptomatic infection and detection of vaccine and vaccine-reassortant rotavirus strains in 5 children: a case series.

    PubMed

    Boom, Julie A; Sahni, Leila C; Payne, Daniel C; Gautam, Rashi; Lyde, Freda; Mijatovic-Rustempasic, Slavica; Bowen, Michael D; Tate, Jacqueline E; Rench, Marcia A; Gentsch, Jon R; Parashar, Umesh D; Baker, Carol J

    2012-10-01

    Vaccine or vaccine-reassortant rotavirus strains were detected in fecal specimens from 5 of 106 (4.7%) immunocompetent children who required treatment for rotavirus gastroenteritis at a large pediatric hospital in Texas in 2009-2010. Four strains were related to pentavalent rotavirus vaccine, whereas one was related to monovalent rotavirus vaccine. The contribution of these strains to each patient's illness was unclear given that 2 patients had prominent respiratory symptoms and 2 were concurrently infected with another pathogen (group F adenovirus and norovirus). Continued monitoring is necessary to assess the role of vaccine strains and vaccine-reassortant strains in pediatric rotavirus infections.

  5. Symptomatic Infection and Detection of Vaccine and Vaccine-Reassortant Rotavirus Strains in 5 Children: A Case Series

    PubMed Central

    Boom, Julie A.; Sahni, Leila C.; Payne, Daniel C.; Gautam, Rashi; Lyde, Freda; Mijatovic-Rustempasic, Slavica; Bowen, Michael D.; Tate, Jacqueline E.; Rench, Marcia A.; Gentsch, Jon R.; Parashar, Umesh D.; Baker, Carol J.

    2015-01-01

    Vaccine or vaccine-reassortant rotavirus strains were detected in fecal specimens from 5 of 106 (4.7%) immunocompetent children who required treatment for rotavirus gastroenteritis at a large pediatric hospital in Texas in 2009–2010. Four strains were related to pentavalent rotavirus vaccine, whereas one was related to monovalent rotavirus vaccine. The contribution of these strains to each patient’s illness was unclear given that 2 patients had prominent respiratory symptoms and 2 were concurrently infected with another pathogen (group F adenovirus and norovirus). Continued monitoring is necessary to assess the role of vaccine strains and vaccine-reassortant strains in pediatric rotavirus infections. PMID:22872730

  6. Identification of Strain-Specific Sequences That Distinguish a Mycoplasma gallisepticum Vaccine Strain from Field Isolates

    PubMed Central

    Ricketts, Camir; Pickler, Larissa; Maurer, John; Ayyampalayam, Saravanaraj; García, Maricarmen

    2016-01-01

    ABSTRACT Despite attempts to control avian mycoplasmosis through management, vaccination, and surveillance, Mycoplasma gallisepticum continues to cause significant morbidity, mortality, and economic losses in poultry production. Live attenuated vaccines are commonly used in the poultry industry to control avian mycoplasmosis; unfortunately, some vaccines may revert to virulence and vaccine strains are generally difficult to distinguish from natural field isolates. In order to identify genome differences among vaccine revertants, vaccine strains, and field isolates, whole-genome sequencing of the M. gallisepticum vaccine strain ts-11 and several “ts-11-like” strains isolated from commercial flocks was performed using Illumina and 454 pyrosequencing and the sequenced genomes compared to the M. gallisepticum Rlow reference genome. The collective contigs for each strain were annotated using the fully annotated Mycoplasma reference genome. The analysis revealed genetic differences among vlhA alleles, as well as among genes annotated as coding for a cell wall surface anchor protein (mg0377) and a hypothetical protein gene, mg0359, unique to M. gallisepticum ts-11 vaccine strain. PCR protocols were designed to target 5 sequences unique to the M. gallisepticum ts-11 strain: vlhA3.04a, vlhA3.04b, vlhA3.05, mg0377, and mg0359. All ts-11 isolates were positive for the five gene alleles tested by PCR; however, 5 to 36% of field isolates were also positive for at least one of the alleles tested. A combination of PCR tests for vlhA3.04a, vlhA3.05, and mg0359 was able to distinguish the M. gallisepticum ts-11 vaccine strain from field isolates. This method will further supplement current approaches to quickly distinguish M. gallisepticum vaccine strains from field isolates. PMID:27847370

  7. Mismatching between circulating strains and vaccine strains of influenza: Effect on Hajj pilgrims from both hemispheres.

    PubMed

    Alfelali, Mohammad; Khandaker, Gulam; Booy, Robert; Rashid, Harunor

    2016-03-03

    The trivalent seasonal influenza vaccine is expected to provide optimum protection if the vaccine strains match the circulating strains. The effect of worldwide mismatch between the vaccine strains and extant strains on travelers attending Hajj pilgrimage is not known. Annually 2-3 million Muslims coming from north and south hemispheres congregate at Hajj in Mecca, Saudi Arabia, where intense congestion amplifies the risk of respiratory infection up to eight fold. In order to estimate, to what extent mismatching increases the risk of vaccine failure in Hajj pilgrims, we have examined the global data on influenza epidemiology since 2003, in light of the available data from Hajj. These data demonstrate that globally mismatching between circulating and vaccine strains has occurred frequently over the last 12 years, and the mismatch seems to have affected the Hajj pilgrims, however, influenza virus characteristics were studied only in a limited number of Hajj seasons. When the vaccines are different, dual vaccination of travelers by vaccines for southern and northern hemispheres should be considered for Hajj pilgrims whenever logistically feasible. Consideration should also be given to the use of vaccines with broader coverage, i.e., quadrivalent, or higher immunogenicity. Continuous surveillance of influenza at Hajj is important.

  8. Mismatching between circulating strains and vaccine strains of influenza: Effect on Hajj pilgrims from both hemispheres

    PubMed Central

    Alfelali, Mohammad; Khandaker, Gulam; Booy, Robert; Rashid, Harunor

    2016-01-01

    Abstract The trivalent seasonal influenza vaccine is expected to provide optimum protection if the vaccine strains match the circulating strains. The effect of worldwide mismatch between the vaccine strains and extant strains on travelers attending Hajj pilgrimage is not known. Annually 2-3 million Muslims coming from north and south hemispheres congregate at Hajj in Mecca, Saudi Arabia, where intense congestion amplifies the risk of respiratory infection up to eight fold. In order to estimate, to what extent mismatching increases the risk of vaccine failure in Hajj pilgrims, we have examined the global data on influenza epidemiology since 2003, in light of the available data from Hajj. These data demonstrate that globally mismatching between circulating and vaccine strains has occurred frequently over the last 12 years, and the mismatch seems to have affected the Hajj pilgrims, however, influenza virus characteristics were studied only in a limited number of Hajj seasons. When the vaccines are different, dual vaccination of travelers by vaccines for southern and northern hemispheres should be considered for Hajj pilgrims whenever logistically feasible. Consideration should also be given to the use of vaccines with broader coverage, i.e., quadrivalent, or higher immunogenicity. Continuous surveillance of influenza at Hajj is important. PMID:26317639

  9. [Genetic recombination in vaccine poliovirus: comparative study in strains excreted in course of vaccination by oral poliovirus vaccine and circulating strains].

    PubMed

    Haddad-Boubaker, S; Ould-Mohamed-Abdallah, M V; Ben-Yahia, A; Triki, H

    2010-12-01

    Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility. This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing. Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose. These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  10. Assay of oral vaccination of dogs against rabies in Tunisia with the vaccinal strain SADBern.

    PubMed

    Haddad, N; Ben Khelifa, R; Matter, H; Kharmachi, H; Aubert, M F; Wandeler, A; Blancou, J

    1994-03-01

    The possibility of immunizing dogs orally against rabies, using SADBern, an attenuated strain, was tested on dogs in the field in Tunisia. This strain induced high neutralizing antibody titres and conferred to all vaccinated dogs total resistance against a challenge with a Maghrebian strain. However, an excretion of virus of vaccinal origin was observed in one dog, hampering the use of SADBern in dogs. Nevertheless, this work demonstrates for the first time that dogs in developing countries, especially those which are inaccessible to parenteral vaccination, could be efficiently immunized against rabies by the oral route.

  11. Hereditary Hemochromatosis Restores the Virulence of Plague Vaccine Strains

    PubMed Central

    Quenee, Lauriane E.; Hermanas, Timothy M.; Ciletti, Nancy; Louvel, Helene; Miller, Nathan C.; Elli, Derek; Blaylock, Bill; Mitchell, Anthony; Schroeder, Jay; Krausz, Thomas; Kanabrocki, Joseph; Schneewind, Olaf

    2012-01-01

    Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv−/−) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv−/− mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv−/− mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines. PMID:22896664

  12. Hereditary hemochromatosis restores the virulence of plague vaccine strains.

    PubMed

    Quenee, Lauriane E; Hermanas, Timothy M; Ciletti, Nancy; Louvel, Helene; Miller, Nathan C; Elli, Derek; Blaylock, Bill; Mitchell, Anthony; Schroeder, Jay; Krausz, Thomas; Kanabrocki, Joseph; Schneewind, Olaf

    2012-10-01

    Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv(-/-)) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv(-/-) mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv(-/-) mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines.

  13. Whole genome analysis of Vietnamese G2P[4] rotavirus strains possessing the NSP2 gene sharing an ancestral sequence with Chinese sheep and goat rotavirus strains.

    PubMed

    Do, Loan Phuong; Doan, Yen Hai; Nakagomi, Toyoko; Gauchan, Punita; Kaneko, Miho; Agbemabiese, Chantal; Dang, Anh Duc; Nakagomi, Osamu

    2015-10-01

    Because imminent introduction into Vietnam of a vaccine against Rotavirus A is anticipated, baseline information on the whole genome of representative strains is needed to understand changes in circulating strains that may occur after vaccine introduction. In this study, the whole genomes of two G2P[4] strains detected in Nha Trang, Vietnam in 2008 were sequenced, this being the last period during which virtually no rotavirus vaccine was used in this country. The two strains were found to be >99.9% identical in sequence and had a typical DS-1 like G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation. Analysis of the Vietnamese strains with >184 G2P[4] strains retrieved from GenBank/EMBL/DDBJ DNA databases placed the Vietnamese strains in one of the lineages commonly found among contemporary strains, with the exception of the NSP2 and NSP4 genes. The NSP2 genes were found to belong to a previously undescribed lineage that diverged from Chinese sheep and goat rotavirus strains, including a Chinese rotavirus vaccine strain LLR with 95% nucleotide identity; the time of their most recent common ancestor was 1975. The NSP4 genes were found to belong, together with Thai and USA strains, to an emergent lineage (VIII), adding further diversity to ever diversifying NSP4 lineages. Thus, there is a need to enhance surveillance of locally-circulating strains from both children and animals at the whole genome level to address the effect of rotavirus vaccines on changing strain distribution.

  14. Selection and characterization of vaccine strain for Enterovirus 71 vaccine development.

    PubMed

    Chang, Jui-Yuan; Chang, Cheng-Peng; Tsai, Hutchinson Hau-Pong; Lee, Chen-Dou; Lian, Wei-Cheng; Ih-Jen-Su; Sai, I-Hsi; Liu, Chia-Chyi; Chou, Ai-Hsiang; Lu, Ya-Jung; Chen, Ching-Yao; Lee, Pi-Hsiu; Chiang, Jen-Ron; Chong, Pele Choi-Sing

    2012-01-17

    Enterovirus 71 (EV71) has recently emerged as an important neurotropic virus in Asia because effective medications and prophylactic vaccine against EV71 infection are not available. Based on the success of inactivated poliovirus vaccine, the Vero cell-based chemically inactivated EV71 vaccine candidate could be developed. Identification of EV71 vaccine strain which can grow to high titer in Vero cell and induce cross-genotype virus neutralizing antibody responses represents the first step in vaccine development. In this report we describe the characterization and validation of a clinical isolate E59 belonging to B4 sub-genotype based on VP1 genetic analysis. Before selected as the vaccine strain, the genetic stability of E59 in passage had been analyzed based on the nucleotide sequences obtained from the Master Virus Seed, Working Seed banks and the virus harvested from the production lots, and found to be identical to those found in the original isolate. These results indicate that E59 vaccine strain has strong genetic stability in passage. Using this vaccine strain the prototype EV71 vaccine candidate was produced from 20L of Vero cell grown in serum-containing medium. The production processes were investigated, characterized and quantified to establish the potential vaccine manufacturing process including the time for virus harvest, the membrane for diafiltration and concentration, the gel-filtration chromatography for the down-stream virus purification, and the methods for viral inactivation. Finally, the inactivated virion vaccine candidate containing sub-microgram of viral proteins formulated with alum adjuvant was found to induce strong virus neutralizing antibody responses in mice and rabbits. Therefore, these results provide valuable information for cell-based EV71 vaccine development.

  15. Dominance of Human Innate Immune Responses in Primary Francisella tularensis Live Vaccine Strain Vaccination

    DTIC Science & Technology

    2006-03-31

    Diseases, Bacteriology Division, 425 Porter St, Frederick , MD 21702-5011. Dr Brittingham is the recipient of the National Research Council Fellowship...tularemia vaccine strain) infection by the sera of human recipients of the live tula- remia vaccine. Am J Med Sci 1994;308:83-7. 10. Herzberg VL

  16. Assessment of a strain 19 brucellosis vaccination program in elk

    USGS Publications Warehouse

    Maichak, Eric J.; Scurlock, Brandon M.; Cross, Paul C.; Rogerson, Jared D.; Edwards, William H.; Wise, Benjamin; Smith, Scott G.; Kreeger, Terry J.

    2017-01-01

    Zoonotic diseases in wildlife present substantial challenges and risks to host populations, susceptible domestic livestock populations, and affected stakeholders. Brucellosis, a disease caused by the bacterium Brucella abortus, is endemic among elk (Cervus canadensis) attending winter feedgrounds and adjacent areas of western Wyoming, USA. To minimize transmission of brucellosis from elk to elk and elk to livestock, managers initiated a B. abortus strain 19 ballistic vaccination program in 1985. We used brucellosis prevalence (1971–2015) and reproductive outcome (2006–2015) data collected from female elk attending feedgrounds to assess efficacy of the strain 19 program while controlling for potentially confounding factors such as site and age. From our generalized linear models, we found that seroprevalence of brucellosis was 1) not lower following inception of vaccination; 2) not inversely associated with proportion of juveniles vaccinated over time; 3) not inversely associated with additional yearlings and adults vaccinated over time; and 4) associated more with feeding end-date than proportion of juveniles vaccinated. Using vaginal implant transmitters in adult females that were seropositive for brucellosis, we found little effect of vaccination coverage at reducing reproductive failures (i.e., abortion or stillbirth). Because we found limited support for efficacy of the strain 19 program, we support research to develop an oral vaccine and suggest that continuing other spatio-temporal management actions will be most effective to minimize transmission of brucellosis and reduce dependency of elk on supplemental winter feeding.

  17. Immunogenicity of an inactivated Chinese bovine viral diarrhea virus 1a (BVDV 1a) vaccine cross protects from BVDV 1b infection in young calves.

    PubMed

    Wang, Wei; Shi, Xinchuan; Wu, Yongwang; Li, Xiaoxin; Ji, Ye; Meng, Qingsen; Zhang, Shucheng; Wu, Hua

    2014-08-15

    Bovine viral diarrhea virus (BVDV) 1a and 1b strains are the predominant subgenotypes in China. Because of the genetic and antigenic variability among different BVDV strains, a vaccine effective in one region may fail to protect against infections caused by different virus strains in another region. No BVDV vaccine developed with the predominant strains in China are available. In this study, the immunogenicity of an inactivated Chinese BVDV 1a NM01 vaccine strain was evaluated by challenging with a Chinese BVDV 1b JL strain. Ten 2-4-month-old calves were intramuscularly vaccinated with a single dose of the vaccine strain and boosted with same dose three weeks after the first vaccination, with five mock immunized calves serving as a control group. The average titer of neutralization antibody to BVDV 1a and BVDV 1b of immunized calves reached 1:410 and 1:96, respectively, at 21 days post the second vaccination. Twenty-one days post the second vaccination, all calves were challenged with strain JL. The clinical signs, such as the temperature and leukopenia of the immunized calves and viral shedding, were significantly less than the mock immunized calves after challenging with the virulent BVDV 1b strain, indicating that the BVDV 1a vaccine strain elicited efficacious protection against the endemic BVDV 1b strain in China. To the best of our knowledge, this is the first report of an inactivated BVDV vaccine which demonstrated effective cross-protection against BVDV type 1b infection in China.

  18. Update of inactivated equine influenza vaccine strain in Japan

    PubMed Central

    GAMOH, Koichiro; NAKAMURA, Shigeyuki

    2017-01-01

    Japan established a vaccine selection system, in which a committee evaluates veterinary influenza vaccines to determine if the vaccine should be updated. In 2013, it was concluded that the present equine influenza vaccine strains did not have to be updated, but clade 2 (Fc2) viruses of the Florida sublineage should be included. We collected three Fc2 viruses as candidates and conducted comparative tests. Results indicated that A/equine/Carlow/2011 (H3N8) is not suitable, because of its unstable antigenic characteristics. A comparison between A/equine/Richmond/1/2007 (H3N8) (Richmond/07) and A/equine/Yokohama/aq13/2010 (H3N8) (Yokohama/10) in eggs showed that they shared equal growth properties. Immunogenicity test in mice showed that Yokohama/10 induced higher HI antibody titers than Richmond/07. Therefore, we concluded that Yokohama/10 was the most suitable strain. PMID:28163276

  19. Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

    PubMed

    Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2015-09-01

    Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

  20. The efficacy of Mycoplasma gallisepticum K-strain live vaccine in broiler and layer chickens.

    PubMed

    Ferguson-Noel, N M; Williams, S M

    2015-01-01

    The efficacy of a live Mycoplasma gallisepticum (MG) vaccine candidate (K-strain) was compared to commercially available vaccines in broiler-type chickens (Trial 1) and layer-type chickens (Trial 2). In Trial 1, three-week-old broiler-type chickens were vaccinated via aerosol with K-strain or an F-strain vaccine. The vaccinated chickens and 10 non-vaccinated controls were subsequently challenged with virulent R-strain via aerosol at six weeks post vaccination; both K-strain and F-strain vaccination resulted in significant protection from air sac and tracheal lesions, as well as R-strain colonization (P ≤ 0.05). In Trial 2, commercial layer-type chickens were vaccinated with ts-11 (via eye drop) or K-strain (via aerosol) at 12 weeks of age. At 25 weeks of age these birds were challenged with R-strain via aerosol. The ts-11 and K-strain vaccinated groups both had significantly lower air sac lesion scores and a lower prevalence of ovarian regression after challenge as compared to non-vaccinated chickens (P ≤ 0.05). K-strain vaccination also prevented significant tracheal lesions and R-strain colonization (P ≤ 0.05). K-strain shows great potential as a highly efficacious live MG vaccine in broiler and layer-type chickens for protection of the respiratory and reproductive systems as well as prevention of infection with field strains.

  1. Review of 10 years of clinical experience with Chinese domestic trivalent influenza vaccine Anflu®

    PubMed Central

    Liu, Yan; Wu, Jun-Yu; Wang, Xu; Chen, Jiang-Ting; Xia, Ming; Hu, Wei; Zou, Yong; Yin, Wei-Dong

    2014-01-01

    Influenza viruses cause annual winter epidemics globally and influenza vaccination is most effective way to prevent the disease or severe outcomes from the illness, especially in developing countries. However, the majority of the world’s total production capacity of influenza vaccine is concentrated in several large multinational manufacturers. A safe and effective preventive vaccine for the developing countries is urgent. Anflu®, a Chinese domestic preservative-free, split-virus trivalent influenza vaccine (TIV), was introduced by Sinovac Biotech Ltd. in 2006. Until now, 20.6 million doses worldwide of Anflu® were sold. Since 2003, 13 company-sponsored clinical studies investigating the immunogenicity and safety of Anflu® have been completed, in which 6642 subjects participated and were vaccinated by Anflu®. Anflu® was generally well tolerated in all age groups, and highly immunogenic in healthy adults and elderly and exceeded the licensure criteria in Europe. This review presents and discusses the experience with Anflu® during the past decade. A new Chinese domestic, preservative-free, unadjuvanted, inactivated split-virus trivalent influenza vaccine (TIV), Anflu®, was introduced into human clinical trials in 2003 and then licensed in China in 2006. The vaccine contains 15 µg /0.5 ml hemagglutinin from each of the 3 influenza virus strains (including an H1N1 influenza A virus subtype, an H3N2 influenza A virus subtype, and an influenza B virus) that are expected to be circulating in the up-coming influenza season. The clinical data pertaining to Anflu® will be reviewed and compared with other TIVs available at present. PMID:24104060

  2. Complete Genome Sequences of Bordetella pertussis Vaccine Reference Strains 134 and 10536

    PubMed Central

    Peng, Yanhui; Loparev, Vladimir; Batra, Dhwani; Burroughs, Mark; Johnson, Taccara; Juieng, Phalasy; Rowe, Lori; Tondella, M. Lucia; Williams, Margaret M.

    2016-01-01

    Vaccine formulations and vaccination programs against whooping cough (pertussis) vary worldwide. Here, we report the complete genome sequences of two divergent Bordetella pertussis reference strains used in the production of pertussis vaccines. PMID:27635001

  3. A natural vaccine candidate strain against cholera.

    PubMed

    Liu, Y Q; Qi, G M; Wang, S X; Yu, Y M; Duan, G C; Zhang, L J; Gao, S Y

    1995-12-01

    E1 Tor Vibrio cholerae (EVC) strains may be classified into two kinds-epidemigenic (EEVC) strains and non-epidemigenic (NEEVC) strains-based on a phage-biotyping system. A large number of EEVC strains have been screened for toxigenic and putative colonization attributes. One such naturally occurring strains (designated IEM101) has been found which is devoid of genes encoding cholera toxin (CT), accessory cholera enterotoxin (ACE), zonula occludens toxin (ZOT), but possesses RS1 sequences and toxin-coregulated pilus A gene (icpA) although icpA is poorly expressed. It expresses type B pili but does not possess type C pili. It is an E1 Tor Ogawa strain and does not cause fluid accumulation in rabbit ilcal loop tests. Active immunization of rabbits with strain IEM101 elicited good protection against challenge with virulent strains of V. cholerae O1. Oral administration caused no side effects in 15 human volunteers, colonized the gut for four to ten days and elicited good immune responses.

  4. Hong Kong Chinese parental attitudes towards vaccination and associated socio-demographic disparities.

    PubMed

    Wang, Linda Dong-Ling; Lam, Wendy Wing Tak; Fielding, Richard

    2016-03-14

    Most previous studies on parental attitudes towards vaccination focused on a disease-specific vaccine. In this study we describe general attitudes towards vaccination in Chinese parents and associated socio-demographic disparities. Data were collected from a random sample of 1996 Hong Kong Chinese parents by telephone interviews (response rate 60%). Multiple linear regression analysis was performed. Most parents believed vaccination to be effective (91.6%) and beneficial (78.7%), though many considered optional vaccines unimportant (39.5%) and unnecessary (62.1%). Demographic characteristics associated with parental negative attitudes to vaccination included being female, born in Hong Kong, married, having fewer children, and children ever experienced vaccination side effects. Lower personal income and religious affiliation were associated with more hesitant attitudes towards optional vaccines. Segments of the population hold significantly negative attitudes towards vaccination and optional vaccines, suggesting a need for targeted efforts on vaccination communication in these groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Chinese Helicobacter pylori vaccine: Solution for an old challenge?

    PubMed Central

    Talebi Bezmin Abadi, Amin; Lee, Yeong Yeh

    2016-01-01

    Helicobacter pylori (H. pylori) is an important cause for gastric cancer in high risk individuals. H. pylori colonizes more than 50% of the world’s population and associated peptic ulcer disease and gastric malignancy have important public health implications. It has been classified as a class I carcinogen in 1994 by the World Health Organization. Clinicians are often prompted to eliminate the infection the moment it is detected. This also, unfortunately, led to reckless use of antibiotics and reports of increasing resistance are now worldwide. Each year, many of people die from gastric cancer; thus application of effective vaccine can reduce this relatively high mortality worldwide. H. pylori can be eliminated by antibiotics but efficacy is sharply decreasing. Moreover, current therapy is also expensive and with side effects. Vaccine may be the best solution to the above problem but there are many challenges in producing such an effective therapeutic vaccine. Recently, the Chinese group published in Lancet, a single-center, randomized, phase III study of an oral recombinant vaccine (Urease B subunit fused with heat-labile enterotoxin B derived from Escherichia coli) prescribed in the Chinese children (6-15 years) without a history of H. pylori infection. This review provides an insight into this new solution for an old challenge. PMID:27602242

  6. Chinese Helicobacter pylori vaccine: Solution for an old challenge?

    PubMed

    Talebi Bezmin Abadi, Amin; Lee, Yeong Yeh

    2016-08-06

    Helicobacter pylori (H. pylori) is an important cause for gastric cancer in high risk individuals. H. pylori colonizes more than 50% of the world's population and associated peptic ulcer disease and gastric malignancy have important public health implications. It has been classified as a class I carcinogen in 1994 by the World Health Organization. Clinicians are often prompted to eliminate the infection the moment it is detected. This also, unfortunately, led to reckless use of antibiotics and reports of increasing resistance are now worldwide. Each year, many of people die from gastric cancer; thus application of effective vaccine can reduce this relatively high mortality worldwide. H. pylori can be eliminated by antibiotics but efficacy is sharply decreasing. Moreover, current therapy is also expensive and with side effects. Vaccine may be the best solution to the above problem but there are many challenges in producing such an effective therapeutic vaccine. Recently, the Chinese group published in Lancet, a single-center, randomized, phase III study of an oral recombinant vaccine (Urease B subunit fused with heat-labile enterotoxin B derived from Escherichia coli) prescribed in the Chinese children (6-15 years) without a history of H. pylori infection. This review provides an insight into this new solution for an old challenge.

  7. [New cold-adapted donor strains for live influenza vaccine].

    PubMed

    Gendon, Iu Z; Markushin, S G; Tsfasman, T M; Akopova, I I; Akhmatova, N K; Koptiaeva, I B

    2013-01-01

    Cold-adapted (CA) strains A/Krasnodar/35 and B/Victoria/63 were isolated using passages of A/Krasnodar/101/59 and B/Victoria/2/87 wild type strains at low temperatures. The resulting CA strains possessed TS and CA phenotypes and had a reduced ability to reproduce in mouse lungs and nasal turbinates. They displayed a high protective efficacy in experiments on mice. The two CA strains reproduced well in chick embryos and MDCK cell line without change of TS and CA markers. The CA A/Krasnodar/35 strain during passages at low temperature acquired 13 mutations in the 6 internal genes, 8 of those mutations led to amino acid changes. The CA B/Victoria/63 strain acquired 8 mutations in the internal genes, 6 of which led to amino acid changes. The intranasal vaccination of mice with the CA A/Krasnodar/35 strain led to a transitory suppression of various lymphocyte subpopulations, as well as to an increase in the number of some other cell types. The CA strains in question may be used in the future as attenuation donors for live influenza vaccines.

  8. Efficacy of vaccination with La Sota strain vaccine to control Newcastle disease in village chickens in Nepal.

    PubMed

    Shrestha, Sulochana; Dhawan, Mamta; Donadeu, Meritxell; Dungu, Baptiste

    2017-02-01

    The efficacy of vaccination with Newcastle disease (ND) La Sota and R2B (Mukteswar) modified live strain vaccines was determined by experimental challenge and with ND La Sota vaccine under field conditions in Nepal. Booster vaccination with ND La Sota vaccine after a primary vaccination with ND La Sota vaccine, induced a geometric mean titre (GMT) of 5.0 log2 haemagglutination inhibition (HI) units, compared to a GMT of 6.0 log2 HI units following booster vaccination with R2B vaccine 1 month after primary vaccination with ND La Sota vaccine. Both vaccines provided 100% protection against challenge with a local field ND strain. Furthermore, booster vaccination with ND La Sota vaccine induced protective levels of antibody after field use in villages in Jhapa, and no outbreaks of ND occurred during the study period. The ND La Sota modified live vaccine is immunogenic and efficacious and is a suitable vaccine for use in vaccination programmes in village chickens in the rural areas of Nepal.

  9. Molecular typing of Brucella melitensis endemic strains and differentiation from the vaccine strain Rev-1.

    PubMed

    Noutsios, Georgios T; Papi, Rigini M; Ekateriniadou, Loukia V; Minas, Anastasios; Kyriakidis, Dimitrios A

    2012-03-01

    In the present study forty-four Greek endemic strains of Br. melitensis and three reference strains were genotyped by Multi locus Variable Number Tandem Repeat (ML-VNTR) analysis based on an eight-base pair tandem repeat sequence that was revealed in eight loci of Br. melitensis genome. The forty-four strains were discriminated from the vaccine strain Rev-1 by Restriction Fragment Length Polymorphism (RFLP) and Denaturant Gradient Gel Electrophoresis (DGGE). The ML-VNTR analysis revealed that endemic, reference and vaccine strains are genetically closely related, while most of the loci tested (1, 2, 4, 5 and 7) are highly polymorphic with Hunter-Gaston Genetic Diversity Index (HGDI) values in the range of 0.939 to 0.775. Analysis of ML-VNTRs loci stability through in vitro passages proved that loci 1 and 5 are non stable. Therefore, vaccine strain can be discriminated from endemic strains by allele's clusters of loci 2, 4, 6 and 7. RFLP and DGGE were also employed to analyse omp2 gene and reveled different patterns among Rev-1 and endemic strains. In RFLP, Rev-1 revealed three fragments (282, 238 and 44 bp), while endemic strains two fragments (238 and 44 bp). As for DGGE, the electrophoretic mobility of Rev-1 is different from the endemic strains due to heterologous binding of DNA chains of omp2a and omp2b gene. Overall, our data show clearly that it is feasible to genotype endemic strains of Br. melitensis and differentiate them from vaccine strain Rev-1 with ML-VNTR, RFLP and DGGE techniques. These tools can be used for conventional investigations in brucellosis outbreaks.

  10. Identification of upregulated genes in a modified live vaccine strain of Edwardsiella ictaluri compared to a virulent parent strain and characterization of novel DNA vaccine candidates

    USDA-ARS?s Scientific Manuscript database

    Using PCR-select subtractive cDNA hybridization technique, 41 expressed sequence tags (EST's) were isolated from a modified live vaccine strain (AQUAVAC-ESC formerly RD-33) vs a virulent parent strain (EILO) of Edwardsiella ictaluri. Transcriptional levels of the 41 ESTs in the vaccine strain and th...

  11. Genogrouping of vaccine breakdown strains (VBS) of feline calicivirus in Japan.

    PubMed

    Ohe, K; Sakai, S; Takahasi, T; Sunaga, F; Murakami, M; Kiuchi, A; Fukuyama, M; Furuhata, K; Hara, M; Ishikawa, Y; Taneno, A

    2007-05-01

    Although prevention of feline calcivirus (FCV) infection by vaccination has been attempted, and isolation of FCV, development of the disease, and a few fatal cases in vaccinated cats have been reported. Fifteen FCV strains isolated from cats that had been vaccinated with commercially available FCV vaccines (F9, FCV-255, and FC-7) were genogrouped. Molecular analysis of viral genomes involved the construction of a phylogenetic tree of capsid genes using the NJ method. Cat anti-F9 serum and rabbit anti-FCV-255 serum were used for virus neutralization tests. Molecular phylogenetic analysis of the amino acid sequences of 15 virus isolates and those of the previously published and GenBank-deposited 9 global and 14 Japanese strains showed that 8 (53%) of the 15 virus isolates as well as the vaccine strains F9 and FCV-255 belonged to genogroup I (G(A)I), and 7 (47%) belonged to genogroup II (G(A)II). Of the 8 G(A)I strains, 2 were isolated from cats that had been vaccinated with an F9 strain live vaccine, 5 from cats vaccinated with an FCV-255-derived vaccine, and 1 from a cat vaccinated with an FC-7-derived vaccine. Of the 7 GAll strains, 5 were isolated from cats that had been vaccinated with the F9 strain live vaccine, 1 from a cat vaccinated with the FCV-255-derived vaccine, and 1 from a cat vaccinated with the FC-7-derived vaccine. These results indicate that more vaccine breakdown strains isolated from the cats vaccinated with the F9 strain-derived vaccine belong to G(A)II than to G(A)I, whereas more vaccine breakdown strains isolated from the cats vaccinated with the FCV-255 strain-derived vaccine belong to G(A)I than to G(A)II, and that when the FC-7 strain-derived vaccine is used, the vaccine breakdown strains belong almost equally to G(A)I and G(A)II. Thus, the genogroups of virus isolates varied with the vaccine strain used (p < 0.05). On the other hand, the neutralizing titres of feline anti-F9 serum and rabbit anti-FCV-255 serum against the 15 isolates were

  12. Pathogenic characteristics of Marek's disease virus field strains prevalent in China and the effectiveness of existing vaccines against them.

    PubMed

    Zhang, Yan-ping; Li, Zhi-jie; Bao, Ke-yan; Lv, Hong-chao; Gao, Yu-long; Gao, Hong-lei; Qi, Xiao-le; Cui, Hong-yu; Wang, Yong-qiang; Ren, Xian-gang; Wang, Xiao-mei; Liu, Chang-jun

    2015-05-15

    The virulence of Marek's disease virus (MDV) is continuously evolving, and more virulent MDV pathotypes are emerging, thereby reducing the effectiveness of the existing vaccines. In this study, feather pulps were collected from diseased chickens in commercial chicken flocks in China that presented significant MD visceral tumors in 2011 and were inoculated into a monolayer of duck embryo fibroblasts (DEFs). Three field isolates of MDV were obtained by plaque cloning and identified as MDV via PCR and designated strains LCC, LLY, and LTS. Unvaccinated and CVI988 vaccine-vaccinated specific pathogen-free chickens were challenged at 7 days post vaccination (dpv) with 1000 plaque forming units of each of the respective MDV isolates. These strains induced gross MD lesions in all (100%) of the unvaccinated chickens, and the mortality rates of the unvaccinated chickens were 42.9%, 46.7%, and 23.1% by 60 days post challenge (dpc), respectively. The CVI988 vaccine induced protective indices (PIs) of 85.7, 92.3, and 66.7, respectively. These results showed that the pathogenic characteristics of the Chinese isolates were diverse and that vaccine CVI988 provided different levels of protection against them. These data indicated that the existence of variant MDV strains was a possible reason of immunity failure in China. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Titration of individual strains in trivalent live-attenuated influenza vaccine without neutralization.

    PubMed

    Sirinonthanawech, Naraporn; Surichan, Somchaiya; Namsai, Aphinya; Puthavathana, Pilaipan; Auewarakul, Prasert; Kongchanagul, Alita

    2016-11-01

    Formulation and quality control of trivalent live-attenuated influenza vaccine requires titration of infectivity of individual strains in the trivalent mix. This is usually performed by selective neutralization of two of the three strains and titration of the un-neutralized strain in cell culture or embryonated eggs. This procedure requires standard sera with high neutralizing titer against each of the three strains. Obtaining standard sera, which can specifically neutralize only the corresponding strain of influenza viruses and is able to completely neutralize high concentration of virus in the vaccine samples, can be a problem for many vaccine manufacturers as vaccine stocks usually have very high viral titers and complete neutralization may not be obtained. Here an alternative approach for titration of individual strain in trivalent vaccine without the selective neutralization is presented. This was done by detecting individual strains with specific antibodies in an end-point titration of a trivalent vaccine in cell culture. Similar titers were observed in monovalent and trivalent vaccines for influenza A H3N2 and influenza B strains, whereas the influenza A H1N1 strain did not grow well in cell culture. Viral interference among the vaccine strains was not observed. Therefore, providing that vaccine strains grow well in cell culture, this assay can reliably determine the potency of individual strains in trivalent live-attenuated influenza vaccines.

  14. Development of live attenuated influenza vaccines against pandemic influenza strains.

    PubMed

    Coelingh, Kathleen L; Luke, Catherine J; Jin, Hong; Talaat, Kawsar R

    2014-07-01

    Avian and animal influenza viruses can sporadically transmit to humans, causing outbreaks of varying severity. In some cases, further human-to-human virus transmission does not occur, and the outbreak in humans is limited. In other cases, sustained human-to-human transmission occurs, resulting in worldwide influenza pandemics. Preparation for future pandemics is an important global public health goal. A key objective of preparedness is to gain an understanding of how to design, test, and manufacture effective vaccines that could be stockpiled for use in a pandemic. This review summarizes results of an ongoing collaboration to produce, characterize, and clinically test a library of live attenuated influenza vaccine strains (based on Ann Arbor attenuated Type A strain) containing protective antigens from influenza viruses considered to be of high pandemic potential.

  15. Genetic strain modification of a live rabies virus vaccine widely used in Europe for wildlife oral vaccination.

    PubMed

    Cliquet, Florence; Robardet, Emmanuelle; Picard Meyer, Evelyne

    2013-10-01

    In Europe, the main reservoir and vector of rabies has been the red fox (Vulpes vulpes). Oral immunization of foxes with live vaccines, using attenuated rabies strains (SAD B19, SAD Bern), apathogenic mutants of an attenuated strain (SAG2) and the vaccinia-rabies glycoprotein recombinant virus vaccine (V-RG), has been shown to be the most effective method for the control and elimination of rabies. Among all vaccines currently used for wildlife oral vaccination, one vaccine (marketed as SAD Bern strain) has been widely used in Europe since 1992 with the distribution of 17million of baits in 2011. Because of the potential environmental safety risk of a live virus which could revert to virulence, the full genome sequencing of this vaccine was undertaken and the sequence was characterized and compared with those of referenced rabies viruses. The vaccine showed higher similarity to the strains belonging to the SAD B19 vaccine virus strains than to the SAD Bern vaccines. This study is the first one reporting on virus strain identity changes in this attenuated vaccine.

  16. Vaccine-induced rabies case in a cow (Bos taurus): Molecular characterisation of vaccine strain in brain tissue.

    PubMed

    Vuta, Vlad; Picard-Meyer, Evelyne; Robardet, Emmanuelle; Barboi, Gheorghe; Motiu, Razvan; Barbuceanu, Florica; Vlagioiu, Constantin; Cliquet, Florence

    2016-09-22

    Rabies is a fatal neuropathogenic zoonosis caused by the rabies virus of the Lyssavirus genus, Rhabdoviridae family. The oral vaccination of foxes - the main reservoir of rabies in Europe - using a live attenuated rabies virus vaccine was successfully conducted in many Western European countries. In July 2015, a rabies vaccine strain was isolated from the brain tissues of a clinically suspect cow (Bos taurus) in Romania. The nucleotide analysis of both N and G gene sequences showed 100% identity between the rabid animal, the GenBank reference SAD B19 strain and five rabies vaccine batches used for the national oral vaccination campaign targeting foxes.

  17. Evaluation and improvement of a single nucleotide polymorphism-based PCR assay for rapid differentiation of live attenuated vaccine strains from field isolates of Erysipelothrix rhusiopathiae.

    PubMed

    Zhu, Weifeng; Li, Jingtao; Wang, Ya; Kang, Chao; Jin, Meilin; Chen, Huanchun

    2016-11-01

    A single nucleotide polymorphism-based PCR assay has been developed to differentiate the attenuated vaccine strain used in Japan from field isolates of Erysipelothrix rhusiopathiae found in pigs. However, this assay has been evaluated with only Japanese strains and isolates; therefore, it is unknown whether it could be used in other countries with E. rhusiopathiae strains and isolates of different genetic backgrounds. In our study, the PCR assay was evaluated using Chinese E. rhusiopathiae vaccine strains and field isolates. The PCR assay was able to differentiate the attenuated vaccine strains from the field isolates of E. rhusiopathiae in China but with a pattern different from that observed in Japan (only a single nucleotide polymorphism was detected in the Chinese vaccine strains compared with 5 in the Japanese vaccine strains). Importantly, either a DNA polymerase without 3' to 5' exonuclease activity or an exo(+) polymerase with an antibody inhibiting the proofreading activity was required. In conclusion, after evaluation and improvement, this fast differentiation assay can be extended from Japan to China.

  18. A Wide Extent of Inter-Strain Diversity in Virulent and Vaccine Strains of Alphaherpesviruses

    PubMed Central

    Szpara, Moriah L.; Tafuri, Yolanda R.; Parsons, Lance; Shamim, S. Rafi; Verstrepen, Kevin J.; Legendre, Matthieu; Enquist, L. W.

    2011-01-01

    Alphaherpesviruses are widespread in the human population, and include herpes simplex virus 1 (HSV-1) and 2, and varicella zoster virus (VZV). These viral pathogens cause epithelial lesions, and then infect the nervous system to cause lifelong latency, reactivation, and spread. A related veterinary herpesvirus, pseudorabies (PRV), causes similar disease in livestock that result in significant economic losses. Vaccines developed for VZV and PRV serve as useful models for the development of an HSV-1 vaccine. We present full genome sequence comparisons of the PRV vaccine strain Bartha, and two virulent PRV isolates, Kaplan and Becker. These genome sequences were determined by high-throughput sequencing and assembly, and present new insights into the attenuation of a mammalian alphaherpesvirus vaccine strain. We find many previously unknown coding differences between PRV Bartha and the virulent strains, including changes to the fusion proteins gH and gB, and over forty other viral proteins. Inter-strain variation in PRV protein sequences is much closer to levels previously observed for HSV-1 than for the highly stable VZV proteome. Almost 20% of the PRV genome contains tandem short sequence repeats (SSRs), a class of nucleic acids motifs whose length-variation has been associated with changes in DNA binding site efficiency, transcriptional regulation, and protein interactions. We find SSRs throughout the herpesvirus family, and provide the first global characterization of SSRs in viruses, both within and between strains. We find SSR length variation between different isolates of PRV and HSV-1, which may provide a new mechanism for phenotypic variation between strains. Finally, we detected a small number of polymorphic bases within each plaque-purified PRV strain, and we characterize the effect of passage and plaque-purification on these polymorphisms. These data add to growing evidence that even plaque-purified stocks of stable DNA viruses exhibit limited sequence

  19. Immune responses of elk to vaccination with Brucella abortus strain RB51.

    PubMed

    Olsen, Steven C; Kreeger, Terry J; Palmer, Mitchell V

    2002-10-01

    In a study conducted from January to August 2000, elk (Cervus elaphus) were vaccinated with Brucella abortus strain RB51 (SRB51, n = 6) or injected with 0.15 M NaCl solution (n = 3) at approximately 6 mo of age. Beginning at 2 wk and continuing to 25 wk after vaccination, SRB51-vaccinated elk had greater antibody responses (P < 0.05) to SRB51 when compared to nonvaccinated elk. Peripheral blood mononuclear cells (PBMC) from SRB51-vaccinated elk had greater (P < 0.05) proliferative responses to SRB51 at 18 wk after vaccination when compared to responses of nonvaccinated elk. Strain RB51 was recovered from blood samples of all vaccinates at 2 wk, and three of six vaccinates at 4 wk after vaccination. The SRB51 vaccine strain was recovered from the superficial cervical lymph node of all vaccinates sampled at 6 wk after vaccination. but not from lymph node samples obtained from vaccinates at 12 or 18 wk after vaccination. At 34 wk after vaccination, SRB51 was recovered from the bronchial lymph node of one of five vaccinates but not from other tissues. Strain RB51 was not recovered at any time from samples obtained from nonvaccinated elk. This study suggests that following vaccination with SRB51, elk remain bacteremic for a prolonged period of time, rapidly develop high antibody titers, and are slower to develop detectable proliferative responses in PBMC when compared to responses of cattle or bison (Bison bison).

  20. Immune responses of bison and efficacy after booster vaccination with Brucella abortus strain RB51

    USDA-ARS?s Scientific Manuscript database

    Thirty-one bison heifers were randomly assigned to saline (control; n=7) or single vaccination (n=24) with 1010 CFU of B. abortus strain RB51 (RB51). Some vaccinated bison were randomly selected for booster vaccination with 10**10 CFU of RB51 at 11 months after initial vaccination (n=16). When comp...

  1. A dual-strain feline calicivirus vaccine stimulates broader cross-neutralization antibodies than a single-strain vaccine and lessens clinical signs in vaccinated cats when challenged with a homologous feline calicivirus strain associated with virulent systemic disease.

    PubMed

    Huang, Chengjin; Hess, Jennifer; Gill, Michael; Hustead, David

    2010-02-01

    Feline calicivirus (FCV) causes an array of clinical disease in cats. Traditionally this disease has been associated with respiratory disease, limping, or chronic stomatitis. Within the last 10 years, virulent systemic feline calicivirus (VS-FCV) has been recognized which causes additional clinical signs and has a higher fatality rate. A dual-strain FCV vaccine containing a strain of FCV associated with traditional respiratory disease and a VS-FCV strain stimulates serum cross-neutralization antibodies when tested against field strains from Europe and VS-FCV strains from USA. Following challenge with a homologous VS-FCV strain, vaccinated cats had significantly reduced clinical signs.

  2. Complete Genome Sequence of Japanese Vaccine Strain LA-AKO of Rinderpest Virus

    PubMed Central

    Takamatsu, Hitomi; Terui, Kazuya

    2015-01-01

    Rinderpest vaccine strain LA-AKO, which is less virulent especially to highly susceptible Asian cattle breeds, was established from a lapinized vaccine strain by further passages in rabbit and chick embryos. Here, we report the genome sequence of LA-AKO, which currently remains active for the production of an emergent vaccine in Japan. PMID:26337882

  3. Use of antigenic cartography in vaccine seed strain selection.

    PubMed

    Fouchier, Ron A M; Smith, Derek J

    2010-03-01

    Human influenza A viruses are classic examples of antigenically variable pathogens that have a seemingly endless capacity to evade the host's immune response. The viral hemagglutinin (HA) and neuraminidase (NA) proteins are the main targets of our antibody response to combat infections. HA and NA continuously change to escape from humoral immunity, a process known as antigenic drift. As a result of antigenic drift, the human influenza vaccine is updated frequently. The World Health Organization (WHO) coordinates a global influenza surveillance network that, by the hemagglutination inhibition (HI) assay, routinely characterizes the antigenic properties of circulating strains in order to select new seed viruses for such vaccine updates. To facilitate a quantitative interpretation and easy visualization of HI data, a new computational technique called "antigenic cartography" was developed. Since its development, antigenic cartography has been applied routinely to assist the WHO with influenza surveillance activities. Until recently, antigenic variation was not considered a serious issue with influenza vaccines for poultry. However, because of the diversification of the Asian H5N1 lineage since 1996 into multiple genetic clades and subclades, and because of the long-term use of poultry vaccines against H5 in some parts of the world, this issue needs to be re-addressed. The antigenic properties of panels of avian H5N1 viruses were characterized by HI assay, using mammalian or avian antisera, and analyzed using antigenic cartography methods. These analyses revealed antigenic differences between circulating H5N1 viruses and the H5 viruses used in poultry vaccines. Considerable antigenic variation was also observed within and between H5N1 clades. These observations have important implications for the efficacy and long-term use of poultry vaccines.

  4. HIV-1 vaccines based on replication-competent Tiantan vaccinia protected Chinese rhesus macaques from simian HIV infection.

    PubMed

    Liu, Qiang; Li, Yue; Luo, Zhenwu; Yang, Guibo; Liu, Yong; Liu, Ying; Sun, Maosheng; Dai, Jiejie; Li, Qihan; Qin, Chuan; Shao, Yiming

    2015-03-27

    To assess the efficacy of HIV vaccines constructed from replication-competent Tiantan vaccinia virus (rTV) alone or combined with DNA in protecting Chinese rhesus macaques from homologous Simian/Human Immunodeficiency Virus (SHIV)-CN97001 challenge. The nef, gag, pol, and gp140 genes from strain CRF07_BC HIV-1 CN54 were selected to construct an HIV vaccine using the rTV or rTV/DNA vaccine. After vaccination, the vaccine and control groups were intravenously challenged with SHIV-CN97001 (32 MID50). HIV-specific antibodies and neutralizing antibodies, gp70 V1V2 binding antibodies, and cytotoxic T-lymphocyte responses were measured prospectively after vaccination with an ELISA, a virus infectivity assay in TZM-bl cells, and ELISPOT assays, respectively. Viral RNA was quantified after challenge with real-time reverse transcriptase-PCR (RT-PCR), and protection efficacy was determined with an analysis of CD8 lymphocyte depletion in vivo. Both rTV and DNA/rTV vaccine groups developed strong cellular and humoral responses against HIV-1 CN54 antigens, including Gag and Env, and also developed significant and persistent anti-Env antibodies and neutralizing antibodies after immunization. Both the rTV and DNA/rTV groups were significantly protected against SHIV-CN97001 or displayed lower viremia than the controls. After CD8 lymphocyte depletion, no viremia was detectable in the vaccinated monkeys, but rebounded rapidly in the control animals. Protection against infection correlated with vaccine-elicited neutralizing antibodies specific for homologous HIV-1 viruses. An rTV-based HIV-1 vaccine, with or without a DNA primer, provided protection from SHIV challenge in a macaque model. Replication-competent Tiantan vaccinia is a promising vector and should enable advances in HIV-1 vaccine development.

  5. Safety and immunogenicity of 3 seasonal trivalent influenza vaccines in the Chinese military.

    PubMed

    Gao, Dongqi; Yang, Huisuo; Deng, Bing; Yin, Gang; Song, Wenjing; Zhang, Haiyang; Li, Yapin

    2016-10-02

    Influenza, caused by the influenza virus, is a contagious acute viral respiratory disease with a high incidence rate and wide and rapid spread. Influenza-related morbidity, mortality, and hospitalization rates remain high and are increasing continuously in high-risk groups, with a significant impact on human health and the economy. In order to evaluate the immunogenicity of 3 seasonal trivalent influenza vaccines in Chinese military, we conducted this field trial. We assessed the safety and immunogenicity of 3 seasonal trivalent influenza vaccines(TIVs)manufactured by GlaxoSmithKline(GSK), Beijing Sinovac Biotech (Sinovac), and Shenzhen Sanofi Pasteur (Pasteur) in healthy Chinese servicemen. We used theimported GSKTIV as the control, comparing it with the 2 domestic TIVs in a 1:1:1randomized, double-blind, controlled trial in a military command in Beijing. Healthy individuals, aged between 18 and 34 years, who had not received any influenza vaccine in the preceding3 years were enrolled and administered one dose of a TIV. Safety data were collected throughout the whole study (day 0 to day 30). Blood samples were collected to assess the subjects' immunogenicity before vaccination and 21 d after vaccination. In total, 292 subjects enrolled in the study. Twelve participants (4.1%) reported 12 adverse events. The incidence of adverse events was 1%, 5%, and7% for the GSK, Sinovac, and Pasteur TIVs, respectively. The reported injection-site reaction frequencies were similar for all 3 TIVs (p = 0.217). However, the proportion of systemic reactions was higher after the GSKTIV than after the Pasteur or Sinovac TIV (7.1% vs 3.1% or1%, respectively; p = 0.020). Three TIVs satisfied both the European and US Food and Drug Administration criteria for H1N1-179, H1N1-74, H3N2, and B strains based on the post vaccination sero-protection, the sero-conversion rate, and the geometric mean titer ratio. The Sinovac TIV, Pasteur TIV, and GSK TIV were well tolerated and immunogenic in

  6. Fulminant encephalitis associated with a vaccine strain of rubella virus.

    PubMed

    Gualberto, Felipe Augusto Souza; de Oliveira, Maria Isabel; Alves, Venancio A F; Kanamura, Cristina T; Rosemberg, Sérgio; Sato, Helena Keico; Arantes, Benedito A F; Curti, Suely Pires; Figueiredo, Cristina Adelaide

    2013-12-01

    Involvement of the central nervous system is common in measles, but rare in rubella. However, rubella virus (RV) can cause a variety of central nervous system syndromes, including meningitis, encephalitis, Guillain-Barré syndrome and sub acute sclerosing panencephalitis. We report the occurrence of one fatal case of the encephalitis associated with measles-rubella (MR) vaccine during an immunization campaign in São Paulo, Brazil. A 31 year-old-man, previously in good health, was admitted at emergency room, with confusion, agitation, inability to stand and hold his head up. Ten days prior to admission, he was vaccinated with combined MR vaccine (Serum Institute of India) and three days later he developed 'flu-like' illness with fever, myalgia and headache. Results of clinical and laboratory exams were consistent with a pattern of viral encephalitis. During hospitalization, his condition deteriorated rapidly with tetraplegia and progression to coma. On the 3rd day of hospitalization he died. Histopathology confirmed encephalitis and immunohistochemistry was positive for RV on brain tissue. RV was also detected by qPCR and virus isolation in cerebrospinal fluid, brain and other clinical samples. The sequence obtained from the isolated virus was identical to that of the RA 27/3 vaccine strain.

  7. Risk Perceptions, Barriers, and Self-Efficacy of Hepatitis B Screening and Vaccination among Chinese Immigrants

    ERIC Educational Resources Information Center

    Ma, Grace X.; Shive, Steven S.; Toubbeh, Jamil; Wu, Dunli; Wang, Ping

    2006-01-01

    Hepatitis B (HBV) infection is a serious health problem among Asian Americans, including Chinese Americans. This study was conducted to measure the perceptions of risk, barriers, and self-efficacy of HBV screening and vaccination in Chinese immigrants. A cross-sectional study was conducted among 429 Chinese Americans in New York City. A…

  8. Simultaneous vaccination of Chinese applicants for a United States immigrant visa.

    PubMed

    Hua, Li; Hongtao, He; Shunqin, Wang; Jinping, Gao; Jiandong, Chen; Zhaoliang, Lei; Xinwen, Feng

    2008-05-01

    Simultaneous vaccination is still uncommon in China, and many Chinese people are quite concerned about the adverse reactions because few data regarding the adverse reactions of simultaneous vaccination in Chinese people have been reported. The objective of this study was to evaluate the safety of simultaneous vaccination and the frequency of adverse reactions following simultaneous vaccinations in Chinese applicants for a United States immigrant visa. We conducted a prospective observational study in 772 applicants receiving required vaccination in Guangdong International Travel Healthcare Center. The vaccines required for vaccination included diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP), adult formulation tetanus and diphtheria toxoids (Td), haemophilus influenzae type-b conjugate vaccine (Hib), oral polio vaccine (OPV), hepatitis B vaccine (HepB), combined measles mumps rubella vaccine (MMR), varicella vaccine (Var), and influenza vaccine (Inf), pneumococcal polysaccharide vaccine (PPV). Data on adverse reactions were collected by questionnaires. Seven hundred and seventy-two participants have received a total of 2533 doses of different vaccines, and 49.6% of the participants reported adverse reactions within 7 days following vaccination, with 39.8%(307/772) local reactions and 20.2%(156/772) systemic reactions. There were no allergic reactions. Only one vaccinee visited hospital seeking treatment due to fever, and recovered well. The most frequent local reaction was pain at the injection site (260/772, 33.7%), especially in the case of PPV vaccination, 61.2% (63/103) vaccinees who received PPV complained of pain at the site of injection, while the most frequent systemic reaction was fever (84/772, 10.9%). Pain and fever were all temporary reactions and resolved within 72h. Logistic regression analysis found that females experienced adverse reactions more frequently than males [(local reactions: female:male=41.7%(187/448):37%(120/324), p

  9. Efficiency of live attenuated and inactivated rabies viruses in prophylactic and post exposure vaccination against the street virus strain.

    PubMed

    Huang, F; Ahmad, W; Duan, M; Liu, Z; Guan, Z; Zhang, M; Qiao, B; Li, Y; Song, Y; Song, Y; Chen, Y; Amjad Ali, M

    2015-06-01

    Rabies remains an enigmatic and widely discussed global infectious disease and causes an increasing number of deaths. The currently used highly effective prophylactic and post exposure (p.e.) vaccination depends solely upon inexpensive, effective and safe vaccines to counteract the spread of the disease. In this study, the potential of an attenuated Chinese rabies vaccine (SRV9) strain in prophylactic and p.e. vaccination against the street strain of rabies virus (RV) was evaluated in mice. Prophylactic vaccination consisting of one intramuscular (i.m.) dose of SRV9 protected 100% of mice from intracerebral (i.c.) challenge with a lethal dose of the street virus. The latter was detected in the brain of mice at day 6 post challenge by RT-PCR. Post exposure vaccination was performed at days 1, 2, 3, 4, 5 and 6 post infection (p.i.) with either SRV9 or inactivated rabies vaccine. The survival rates after i.m. inoculation of SRV9 at the indicated days were 70%, 50%, 30%, 20%, 10%, and 0%, respectively; the corresponding survival rates for the inactivated rabies vaccine were 30%, 20%, 10%, 0%, 0%, and 0%, respectively. However, 100%, 90%, 70%, 50%, 20%, 10%, and 10% of mice survived after i.c. inoculation of SRV9 at the indicated days. The increased permeability of the blood-brain barrier and the infiltration of CD19+ B cells into the central nervous system after i.c. inoculation of SRV9 are regarded as prerequisites for the clearance of the street virus. The obtained data suggest that SRV9 is a promising candidate for prophylactic and p.e. vaccination against rabies infection and that it exhibits a potential for the control of rabies in China.

  10. Simultaneous analysis of the nasal shedding kinetics of field and vaccine strains of Bordetella bronchiseptica.

    PubMed

    Iemura, R; Tsukatani, R; Micallef, M J; Taneno, A

    2009-12-26

    Groups of four two-week-old puppies were administered serial dilutions of an intranasal vaccine containing live Bordetella bronchiseptica and canine parainfluenza virus vaccine and housed individually in isolator cages. Three vaccinated groups and one unvaccinated control group were exposed to virulent B bronchiseptica four weeks after vaccination and evaluated. Nasal swabs for bacterial culture and sera for agglutination tests were taken from all the dogs every week for four weeks. The bacteria isolated were identified by growth on specific agar and by specific PCR to distinguish between vaccine and challenge strains. The vaccine strain persisted in the nasal cavity after vaccination but no adverse reactions were observed. Serum agglutination titres were raised in the vaccinated dogs at challenge. Vaccine strains were not isolated after the challenge from most of the vaccinated dogs. The challenge strain was shed in the dogs vaccinated with the lowest dose (10(6.0) cfu/dose) for two to three weeks but the other vaccinated groups (10(7.0) and 10(8.0) cfu/dose) shed the challenge strain transiently or not at all. Only the group vaccinated with 10(6.0) cfu/dose exhibited clinical signs after challenge.

  11. Pap testing, awareness, and acceptability of a human papillomavirus (HPV) vaccine among Chinese American women.

    PubMed

    Nguyen, Giang T; Chen, Bei; Chan, Melvin

    2012-10-01

    Little is known about the knowledge and opinions of human papillomavirus (HPV) vaccine among Chinese immigrants, nor the impact of framing HPV as a sexually transmitted infection in this population. A cross-sectional survey was conducted focusing on knowledge and experience with HPV, HPV vaccine, cervical cancer and Pap testing, and attitudes toward HPV vaccine in response to different message frames. Chinese American women were recruited in a community setting (n = 162). Only 19 % had heard of HPV and 38 % had had a Pap test in the last 3 years. Multivariate logistic regression showed that English proficiency was associated with vaccination acceptance and insurance status was associated with HPV awareness; there was no observed correlation with message framing. Chinese American women with limited English proficiency have low HPV awareness. Community-based, culturally appropriate education about cervical cancer and HPV vaccine should be directed toward limited-English proficient Chinese American women.

  12. DIVERGENCE, NOT DIVERSITY OF AN ATTENUATED EQUINE LENTIVIRUS VACCINE STRAIN CORRELATES WITH PROTECTION FROM DISEASE

    PubMed Central

    Craigo, Jodi K.; Barnes, Shannon; Cook, Sheila J.; Issel, Charles J.; Montelaro, Ronald C.

    2010-01-01

    We recently reported an attenuated EIAV vaccine study that directly examined the effect of lentiviral envelope sequence variation on vaccine efficacy. The study [1] demonstrated for the first time the failure of an ancestral vaccine to protect and revealed a significant, inverse, linear relationship between envelope divergence and protection from disease. In the current study we examine in detail the evolution of the attenuated vaccine strain utilized in this previous study. We demonstrate here that the attenuated strain progressively evolved during the six-month pre-challenge period and that the observed protection from disease was significantly associated with divergence from the original vaccine strain. PMID:20955830

  13. Ability of vaccine strain induced antibodies to neutralize field isolates of caliciviruses from Swedish cats.

    PubMed

    Wensman, Jonas Johansson; Samman, Ayman; Lindhe, Anna; Thibault, Jean-Christophe; Berndtsson, Louise Treiberg; Hosie, Margaret J

    2015-12-12

    Feline calicivirus (FCV) is a common cause of upper respiratory tract disease in cats worldwide. Its characteristically high mutation rate leads to escape from the humoral immune response induced by natural infection and/or vaccination and consequently vaccines are not always effective against field isolates. Thus, there is a need to continuously investigate the ability of FCV vaccine strain-induced antibodies to neutralize field isolates. Seventy-eight field isolates of FCV isolated during the years 2008-2012 from Swedish cats displaying clinical signs of upper respiratory tract disease were examined in this study. The field isolates were tested for cross-neutralization using a panel of eight anti-sera raised in four pairs of cats following infection with four vaccine strains (F9, 255, G1 and 431). The anti-sera raised against F9 and 255 neutralised 20.5 and 11.5 %, and 47.4 and 64.1 % of field isolates tested, respectively. The anti-sera against the more recently introduced vaccine strains G1 and 431 neutralized 33.3 and 55.1 % (strain G1) or 69.2 and 89.7 % (strain 431) of the field isolates with titres ≥5. [corrected]. Dual vaccine strains displayed a higher cross-neutralization. This study confirms previous observations that more recently introduced vaccine strains induce antibodies with a higher neutralizing capacity compared to vaccine strains that have been used extensively over a long period of time. This study also suggests that dual FCV vaccine strains might neutralize more field isolates compared to single vaccine strains. Vaccine strains should ideally be selected based on updated knowledge on the antigenic properties of field isolates in the local setting, and there is thus a need for continuously studying the evolution of FCV together with the neutralizing capacity of vaccine strain induced antibodies against field isolates at a national and/or regional level.

  14. Universal or Specific? A Modeling-Based Comparison of Broad-Spectrum Influenza Vaccines against Conventional, Strain-Matched Vaccines

    PubMed Central

    Subramanian, Rahul; Graham, Andrea L.; Grenfell, Bryan T.; Arinaminpathy, Nimalan

    2016-01-01

    Despite the availability of vaccines, influenza remains a major public health challenge. A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza, while novel influenza viruses invade the human population to cause a pandemic every few decades. Current vaccines have to be updated continually to keep up to date with this antigenic change, but emerging ‘universal’ vaccines—targeting more conserved components of the influenza virus—offer the potential to act across all influenza A strains and subtypes. Influenza vaccination programmes around the world are steadily increasing in their population coverage. In future, how might intensive, routine immunization with novel vaccines compare against similar mass programmes utilizing conventional vaccines? Specifically, how might novel and conventional vaccines compare, in terms of cumulative incidence and rates of antigenic evolution of seasonal influenza? What are their potential implications for the impact of pandemic emergence? Here we present a new mathematical model, capturing both transmission dynamics and antigenic evolution of influenza in a simple framework, to explore these questions. We find that, even when matched by per-dose efficacy, universal vaccines could dampen population-level transmission over several seasons to a greater extent than conventional vaccines. Moreover, by lowering opportunities for cross-protective immunity in the population, conventional vaccines could allow the increased spread of a novel pandemic strain. Conversely, universal vaccines could mitigate both seasonal and pandemic spread. However, where it is not possible to maintain annual, intensive vaccination coverage, the duration and breadth of immunity raised by universal vaccines are critical determinants of their performance relative to conventional vaccines. In future, conventional and novel vaccines are likely to play complementary roles in vaccination

  15. Safe Live Oral Salmonella Vaccines; Use of aro- Strains.

    DTIC Science & Technology

    1983-05-20

    Department of the Army position unless so designated by other authorized documents. 7, S"|ECuRITY CLASSIFICATION Or THIS PAGE (W*PR Deem Enteewd) REPORT...properties justifying trial as oral-route vaccine in human volunteers will soon he completed. If such a strain gives satisfactory results, in respect of...biosynthetic (aro) both in biotype and in that it is virulent for calves’?. A nLn- pathway. A complete block at any .step of this pathway should reverting

  16. Experimental study of a further attenuated live measles vaccine of the Sugiyama strain in Iran

    PubMed Central

    Mirchamsy, H.; Shafyi, A.; Rafyi, M. R.; Bahrami, S.; Nazari, P.; Fatemie, S.

    1974-01-01

    After encouraging results of the mass vaccination programme in Iran, in which 5 million children in rural areas were vaccinated with the Japanese Sugiyama strain at its 82nd passage in baby calf kidney, and a progressive decrease in the incidence of measles as well as a reduction of excessive infant mortality, a further attenuated vaccine, produced with the same strain, cloned in Japan, was compared in a field trial with the parent vaccine. The new strain caused fewer reactions than the original strain. Seroconversion with a geometric mean antibody titre of 6·1 was observed in 95% of susceptible children. PMID:4522721

  17. Oral vaccination of badgers (Meles meles) against tuberculosis: comparison of the protection generated by BCG vaccine strains Pasteur and Danish.

    PubMed

    Murphy, Denise; Costello, Eamon; Aldwell, Frank E; Lesellier, Sandrine; Chambers, Mark A; Fitzsimons, Tara; Corner, Leigh A L; Gormley, Eamonn

    2014-06-01

    Vaccination of badgers by the subcutaneous, mucosal and oral routes with the Pasteur strain of Mycobacterium bovis bacille Calmette-Guérin (BCG) has resulted in significant protection against experimental infection with virulent M. bovis. However, as the BCG Danish strain is the only commercially licensed BCG vaccine for use in humans in the European Union it is the vaccine of choice for delivery to badger populations. As all oral vaccination studies in badgers were previously conducted using the BCG Pasteur strain, this study compared protection in badgers following oral vaccination with the Pasteur and the Danish strains. Groups of badgers were vaccinated orally with 10(8) colony forming units (CFU) BCG Danish 1331 (n = 7 badgers) or 10(8) CFU BCG Pasteur 1173P2 (n = 6). Another group (n = 8) served as non-vaccinated controls. At 12 weeks post-vaccination, the animals were challenged by the endobronchial route with 6 × 10(3) CFU M. bovis, and at 15 weeks post-infection, all of the badgers were euthanased. Vaccination with either BCG strain provided protection against challenge compared with controls. The vaccinated badgers had significantly fewer sites with gross pathology and significantly lower gross pathological severity scores, fewer sites with histological lesions and fewer sites of infection, significantly lower bacterial counts in the thoracic lymph node, and lower bacterial counts in the lungs than the control group. No differences were observed between either of the vaccine groups by any of the pathology and bacteriology measures. The ELISPOT analysis, measuring production of badger interferon - gamma (IFN-γ), was also similar across the vaccinated groups.

  18. Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

    PubMed

    Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

    2016-10-01

    Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. A Web-Based Platform for Designing Vaccines against Existing and Emerging Strains of Mycobacterium tuberculosis

    PubMed Central

    Dhanda, Sandeep Kumar; Vir, Pooja; Singla, Deepak; Gupta, Sudheer; Kumar, Shailesh

    2016-01-01

    Development of an effective vaccine against drug-resistant Mycobacterium tuberculosis (Mtb) is crucial for saving millions of premature deaths every year due to tuberculosis. This paper describes a web portal developed for assisting researchers in designing vaccines against emerging Mtb strains using traditional and modern approaches. Firstly, we annotated 59 genomes of Mycobacterium species to understand similarity/dissimilarity between tuberculoid, non-tuberculoid and vaccine strains at genome level. Secondly, antigen-based vaccine candidates have been predicted in each Mtb strain. Thirdly, epitopes-based vaccine candidates were predicted/discovered in above antigen-based vaccine candidates that can stimulate all arms of immune system. Finally, a database of predicted vaccine candidates at epitopes as well at antigen level has been developed for above strains. In order to design vaccine against a newly sequenced genome of Mtb strain, server integrates three modules for identification of strain-, antigen-, epitope-specific vaccine candidates. We observed that 103522 unique peptides (9mers) had the potential to induce an antibody response and/or promiscuous binder to MHC alleles and/or have the capability to stimulate T lymphocytes. In summary, this web-portal will be useful for researchers working on designing vaccines against Mtb including drug-resistant strains. Availability: The database is available freely at http://crdd.osdd.net/raghava/mtbveb/. PMID:27096425

  20. Immune Responses of Bison and Efficacy after Booster Vaccination with Brucella abortus Strain RB51

    PubMed Central

    McGill, J. L.; Sacco, R. E.; Hennager, S. G.

    2015-01-01

    Thirty-one bison heifers were randomly assigned to receive saline or a single vaccination with 1010 CFU of Brucella abortus strain RB51. Some vaccinated bison were randomly selected for booster vaccination with RB51 at 11 months after the initial vaccination. Mean antibody responses to RB51 were greater (P < 0.05) in vaccinated bison after initial and booster vaccination than in nonvaccinated bison. The proliferative responses by peripheral blood mononuclear cells (PBMC) from the vaccinated bison were greater (P < 0.05) than those in the nonvaccinated bison at 16 and 24 weeks after the initial vaccination but not after the booster vaccination. The relative gene expression of gamma interferon (IFN-γ) was increased (P < 0.05) in the RB51-vaccinated bison at 8, 16, and 24 weeks after the initial vaccination and at 8 weeks after the booster vaccination. The vaccinated bison had greater (P < 0.05) in vitro production of IFN-γ at all sampling times, greater interleukin-1β (IL-1β) production in various samplings after the initial and booster vaccinations, and greater IL-6 production at one sampling time after the booster vaccination. Between 170 and 180 days of gestation, the bison were intraconjunctivally challenged with approximately 1 × 107 CFU of B. abortus strain 2308. The incidences of abortion and infection were greater (P < 0.05) in the nonvaccinated bison after experimental challenge than in the bison receiving either vaccination treatment. Booster-vaccinated, but not single-vaccinated bison, had a reduced (P < 0.05) incidence of infection in fetal tissues and maternal tissues compared to that in the controls. Compared to the nonvaccinated bison, both vaccination treatments lowered the colonization (measured as the CFU/g of tissue) of Brucella organisms in all tissues, except in retropharyngeal and supramammary lymph nodes. Our study suggests that RB51 booster vaccination is an effective vaccination strategy for enhancing herd immunity against brucellosis in

  1. Comparative Proteome Analysis of Brucella melitensis Vaccine Strain Rev 1 and a Virulent Strain, 16M

    PubMed Central

    Eschenbrenner, Michel; Wagner, Mary Ann; Horn, Troy A.; Kraycer, Jo Ann; Mujer, Cesar V.; Hagius, Sue; Elzer, Philip; DelVecchio, Vito G.

    2002-01-01

    The genus Brucella consists of bacterial pathogens that cause brucellosis, a major zoonotic disease characterized by undulant fever and neurological disorders in humans. Among the different Brucella species, Brucella melitensis is considered the most virulent. Despite successful use in animals, the vaccine strains remain infectious for humans. To understand the mechanism of virulence in B. melitensis, the proteome of vaccine strain Rev 1 was analyzed by two-dimensional gel electrophoresis and compared to that of virulent strain 16M. The two strains were grown under identical laboratory conditions. Computer-assisted analysis of the two B. melitensis proteomes revealed proteins expressed in either 16M or Rev 1, as well as up- or down-regulation of proteins specific for each of these strains. These proteins were identified by peptide mass fingerprinting. It was found that certain metabolic pathways may be deregulated in Rev 1. Expression of an immunogenic 31-kDa outer membrane protein, proteins utilized for iron acquisition, and those that play a role in sugar binding, lipid degradation, and amino acid binding was altered in Rev 1. PMID:12193611

  2. Comparative proteome analysis of Brucella melitensis vaccine strain Rev 1 and a virulent strain, 16M.

    PubMed

    Eschenbrenner, Michel; Wagner, Mary Ann; Horn, Troy A; Kraycer, Jo Ann; Mujer, Cesar V; Hagius, Sue; Elzer, Philip; DelVecchio, Vito G

    2002-09-01

    The genus Brucella consists of bacterial pathogens that cause brucellosis, a major zoonotic disease characterized by undulant fever and neurological disorders in humans. Among the different Brucella species, Brucella melitensis is considered the most virulent. Despite successful use in animals, the vaccine strains remain infectious for humans. To understand the mechanism of virulence in B. melitensis, the proteome of vaccine strain Rev 1 was analyzed by two-dimensional gel electrophoresis and compared to that of virulent strain 16M. The two strains were grown under identical laboratory conditions. Computer-assisted analysis of the two B. melitensis proteomes revealed proteins expressed in either 16M or Rev 1, as well as up- or down-regulation of proteins specific for each of these strains. These proteins were identified by peptide mass fingerprinting. It was found that certain metabolic pathways may be deregulated in Rev 1. Expression of an immunogenic 31-kDa outer membrane protein, proteins utilized for iron acquisition, and those that play a role in sugar binding, lipid degradation, and amino acid binding was altered in Rev 1.

  3. Humoral response to calicivirus in captive tigers given a dual-strain vaccine.

    PubMed

    Harrison, Tara M; Harrison, Scott H; Sikarskie, James G; Armstrong, Douglas

    2014-03-01

    The current feline vaccine with a single strain of calicivirus has been used for captive tigers, yet it may not protect against virulent systemic calicivirus infections. A cross-institutional study investigated the humoral response to a new dual-strain, killed-virus calicivirus vaccine for nine captive tigers. The subspecies of these tigers were Amur (Panthera tigris altaica), Bengal (Panthera tigris tigris), and Malayan (Panthera tigris jacksoni). Serum neutralization titers for virulent feline calicivirus strain FCV-DD1 were higher following dual-strain vaccine administration. There were no reports of adverse vaccine reactions. Dual-strain vaccination may afford broadened cross-protection against different calicivirus strains and is desirable to reduce the risk of virulent systemic calicivirus disease in tigers.

  4. A gE-negative BHV1 vaccine virus strain cannot perpetuate in cattle populations.

    PubMed

    Mars, M H; de Jong, M C; van Oirschot, J T

    2000-04-14

    Three identical transmission experiments were successively performed to quantitatively evaluate the possible transmission of a gE-negative bovine herpesvirus 1 (BHV1) vaccine strain among cattle. After intranasal inoculation, the vaccine virus was excreted in high titers in nasal fluids. However, the vaccine virus was transmitted to only one sentinel in one experiment, and not to any of the 10 sentinel cattle in the other two experiments. Based on these observations, it can be concluded that the expected number of cases per vaccine-inoculated animal, i.e. the transmission ratio R(0) of the vaccine strain, is significantly below 1. The R(0) was estimated to be 0.14. After intramuscular inoculation, shedding of vaccine virus was not detected. Therefore, we concluded that it is highly unlikely that this live gE-negative BHV1 vaccine strain will perpetuate in the cattle population.

  5. Permissive growth of human adenovirus type 4 vaccine strain-based vector in porcine cell lines.

    PubMed

    Gao, Dong-sheng; Li, Xiao-jing; Wan, Wen-yan; Li, Hong-jie; Wang, Xiao-xue; Yang, Xia; Li, Yong-tao; Chang, Hong-tao; Chen, Lu; Wang, Chuan-qing; Zhao, Jun

    2016-02-01

    In recent years, there has been considerable interest in using adenoviruses as live vectors to develop recombinant vaccines. Previous studies have demonstrated the safety and effectiveness of HIV/SIV and influenza vaccine candidates based on human adenovirus type 4 (Ad4) replication-competent vectors in rhesus macaque and human model. To explore the possibility of human Ad4 vaccine strain used as a vector in developing porcine vaccines, the growth properties of replication-competent human Ad4 vaccine strain recombinant encoding EGFP in different porcine cell lines were investigated. All tested cell lines are permissive for Ad4 vaccine strain vector with varied replication efficiency. Thus, human Ad4 based vectors would be promising supplement to adenovirus vectors as a delivery vehicle for recombinant vaccines in swine industry.

  6. Assessment of attenuated Salmonella vaccine strains in controlling experimental Salmonella Typhimurium infection in chickens.

    PubMed

    Pei, Yanlong; Parreira, Valeria R; Roland, Kenneth L; Curtiss, Roy; Prescott, John F

    2014-01-01

    Salmonella hold considerable promise as vaccine delivery vectors for heterologous antigens in chickens. Such vaccines have the potential additional benefit of also controlling Salmonella infection in immunized birds. As a way of selecting attenuated strains with optimal immunogenic potential as antigen delivery vectors, this study screened 20 novel Salmonella Typhimurium vaccine strains, differing in mutations associated with delayed antigen synthesis and delayed attenuation, for their efficacy in controlling colonization by virulent Salmonella Typhimurium, as well as for their persistence in the intestine and the spleen. Marked differences were observed between strains in these characteristics, which provide the basis for selection for further study as vaccine vectors.

  7. Clinical trials with Alice strain, live, attenuated, serum inhibitor-resistant intranasal influenza A vaccine.

    PubMed

    Spencer, M J; Cherry, J D; Powell, K R; Sumaya, C V; Garakian, A J

    1975-10-01

    Two clinical trials with Alice strain intranasal influenza vaccine were performed. In study no. 1 (utilizing random selection and double-blind control), 50 subjects received a bivalent inactivated influenza vaccine intramuscularly, 99 subjects received Alice strain vaccine intranasally, and 50 subjects received a placebo intranasally. No symptomatology could be attributed to the intranasal route of immunization. Convalescent-phase geometric mean titers of hemagglutination inhibition antibody were higher after intramuscular vaccination; seroconversion occurred in 16 or 17 recipients of the Alice strain, with initial titers of less than 1:8. Clinical and virologic surveillance for 20 weeks after vaccination revealed no influenza A illnesses in participants of the study. In study no. 2, 75% of the subjects with initial nasal antibody titers of less than 1:3 developed measurable nasal antibody after receiving Alice strain vaccine.

  8. Rescue of a vaccine strain of peste des petits ruminants virus: In vivo evaluation and comparison with standard vaccine

    PubMed Central

    Muniraju, Murali; Mahapatra, Mana; Buczkowski, Hubert; Batten, Carrie; Banyard, Ashley C.; Parida, Satya

    2015-01-01

    Across the developing world peste des petits ruminants virus places a huge disease burden on agriculture, primarily affecting the production of small ruminant. The disease is most effectively controlled by vaccinating sheep and goats with live attenuated vaccines that provide lifelong immunity. However, the current vaccines and serological tests are unable to enable Differentiation between naturally Infected and Vaccinated Animals (DIVA). This factor precludes meaningful assessment of vaccine coverage and epidemiological surveillance based on serology, in turn reducing the efficiency of control programmes. The availability of a recombinant PPRV vaccine with a proven functionality is a prerequisite for the development of novel vaccines that may enable the development of DIVA tools for PPRV diagnostics. In this study, we have established an efficient reverse genetics system for PPRV Nigeria 75/1 vaccine strain and, further rescued a version of PPRV Nigeria 75/1 vaccine strain that expresses eGFP as a novel transcription cassette and a version of PPRV Nigeria 75/1 vaccine strain with mutations in the haemagglutinin (H) gene to enable DIVA through disruption of binding to H by the C77 monoclonal antibody used in the competitive (c) H-ELISA. All three rescued viruses showed similar growth characteristics in vitro in comparison to parent vaccine strain and, following in vivo assessment the H mutant provided full protection in goats. Although the C77 monoclonal antibody used in the cH-ELISA was unable to bind to the mutated form of H in vitro, the mutation was not sufficient to enable DIVA in vivo. PMID:25444790

  9. Rescue of a vaccine strain of peste des petits ruminants virus: In vivo evaluation and comparison with standard vaccine.

    PubMed

    Muniraju, Murali; Mahapatra, Mana; Buczkowski, Hubert; Batten, Carrie; Banyard, Ashley C; Parida, Satya

    2015-01-09

    Across the developing world peste des petits ruminants virus places a huge disease burden on agriculture, primarily affecting the production of small ruminant. The disease is most effectively controlled by vaccinating sheep and goats with live attenuated vaccines that provide lifelong immunity. However, the current vaccines and serological tests are unable to enable Differentiation between naturally Infected and Vaccinated Animals (DIVA). This factor precludes meaningful assessment of vaccine coverage and epidemiological surveillance based on serology, in turn reducing the efficiency of control programmes. The availability of a recombinant PPRV vaccine with a proven functionality is a prerequisite for the development of novel vaccines that may enable the development of DIVA tools for PPRV diagnostics. In this study, we have established an efficient reverse genetics system for PPRV Nigeria 75/1 vaccine strain and, further rescued a version of PPRV Nigeria 75/1 vaccine strain that expresses eGFP as a novel transcription cassette and a version of PPRV Nigeria 75/1 vaccine strain with mutations in the haemagglutinin (H) gene to enable DIVA through disruption of binding to H by the C77 monoclonal antibody used in the competitive (c) H-ELISA. All three rescued viruses showed similar growth characteristics in vitro in comparison to parent vaccine strain and, following in vivo assessment the H mutant provided full protection in goats. Although the C77 monoclonal antibody used in the cH-ELISA was unable to bind to the mutated form of H in vitro, the mutation was not sufficient to enable DIVA in vivo.

  10. Protective efficacy of a live, attenuated, influenza virus vaccine (‘Alice’ strain)

    PubMed Central

    Prinzie, A.; Delem, A.; Huygelen, C.

    1976-01-01

    Animal studies have indicated the high degree of efficacy and broad protection of ‘Alice’ vaccine against various heterologous H3N2 influenza virus strains. Similarly, challenge studies carried out in volunteers have confirmed the high degree of efficacy of ‘Alice’ vaccine versus homologous and heterologous influenza A virus strains. PMID:785431

  11. Effectiveness of Meningococcal B Vaccine against Endemic Hypervirulent Neisseria meningitidis W Strain, England

    PubMed Central

    Giuliani, Marzia Monica; Biolchi, Alessia; Pizza, Mariagrazia; Beebeejaun, Kazim; Lucidarme, Jay; Findlow, Jamie; Ramsay, Mary E.; Borrow, Ray

    2016-01-01

    Serum samples from children immunized with a meningococcal serogroup B vaccine demonstrated potent serum bactericidal antibody activity against the hypervirulent Neisseria meningitidis serogroup W strain circulating in England. The recent introduction of this vaccine into the United Kingdom national immunization program should also help protect infants against this endemic strain. PMID:26811872

  12. Herpes zoster caused by vaccine-strain varicella zoster virus in an immunocompetent recipient of zoster vaccine.

    PubMed

    Tseng, Hung Fu; Schmid, D Scott; Harpaz, Rafael; LaRussa, Philip; Jensen, Nancy J; Rivailler, Pierre; Radford, Kay; Folster, Jennifer; Jacobsen, Steven J

    2014-04-01

    We report the first laboratory-documented case of herpes zoster caused by the attenuated varicella zoster virus (VZV) contained in Zostavax in a 68-year-old immunocompetent adult with strong evidence of prior wild-type VZV infection. The complete genome sequence of the isolate revealed that the strain carried 15 of 42 (36%) recognized varicella vaccine-associated single-nucleotide polymorphisms, including all 5 of the fixed vaccine markers present in nearly all of the strains in the vaccine. The case of herpes zoster was relatively mild and resolved without complications.

  13. Controversial results of the genetic analysis of a canine distemper vaccine strain.

    PubMed

    Demeter, Zoltán; Palade, Elena Alina; Hornyák, Akos; Rusvai, Miklós

    2010-05-19

    Canine distemper (CD) is a highly contagious, often fatal, multisystemic viral disease of receptive carnivores. The presence of a PsiI cleavage site on a specific location of the hemagglutinin (H) gene was found to be a hallmark of vaccine strains, thus, a previously published restriction fragment length polymorphism (RFLP) test using PsiI theoretically allows the distinction between all currently used vaccine strains and virulent field strains. The RFLP test was carried out on all brands of CD vaccines available in Hungary. The present work describes the extensive sequencing and phylogenetic study of the strain present in Vanguard (Pfizer Animal Health) vaccines, which following the PsiI based RFLP test reacted as a wild-type strain. Based on the product description provided by the manufacturer, all batches should have contained a virus strain (Snyder Hill) belonging to the group of vaccine strains (America-1). Extensive genetic analysis involving the full nucleic acid sequence of four other genes (N, M, P and F) of the CDV genome revealed that the incriminated virus strain showed a higher level of genetic identity to wild-type strains from the America-2 group than to any of the strains belonging to America-1 group, therefore the vaccine does not contain the virus strain stated by the manufacturer in its product description and has not been containing it since at least 1992.

  14. Development of a duplex PCR for rapid detection and differentiation of Erysipelothrix rhusiopathiae vaccine strains and wild type strains.

    PubMed

    Zhu, Weifeng; Wu, Chao; Kang, Chao; Cai, Chengzhi; Jin, Meilin

    2017-02-01

    The differentiation of vaccine strains from wild type strains is important for disease control. A duplex PCR for rapid detection and differentiation of Erysipelothrix rhusiopathiae vaccine strains and wild type strains was developed based on the DNA polymerase IV gene. This duplex PCR was sensitive and specific. The detection results were coincident with that of a single nucleotide polymorphisms based PCR but the detection process was more rapid. In conclusion, this duplex PCR was a useful tool for Erysipelothrix rhusiopathiae infections' differential diagnosis in China.

  15. Genome sequence of Bacillus anthracis attenuated vaccine strain A16R used for human in China.

    PubMed

    Liu, Xiankai; Qi, Xinpeng; Zhu, Li; Wang, Dongshu; Gao, Zhiqi; Deng, Haijun; Wu, Weili; Hu, Tao; Chen, Chen; Chen, Weijun; Wang, Hengliang

    2015-09-20

    An attenuated Bacillus anthracis vaccine strain for human use, A16R, was obtained in China after ultraviolet radiation treatment and continuous subculture of the wild-type strain A16. A16R can synthesize the exotoxin, but without a capsule. We sequenced and annotated the A16R genome to encourage the use of this strain. The genome sequencing of the wild-type strain A16 is underway and the genomic comparison between the two strains will help to illustrate the attenuating mechanism of the A16R vaccine strain.

  16. Virulent and Vaccine Strains of Streptococcus equi ssp. zooepidemicus Have Different Influences on Phagocytosis and Cytokine Secretion of Macrophages.

    PubMed

    Jie, Peng; Zhe, Ma; Chengwei, Hua; Huixing, Lin; Hui, Zhang; Chengping, Lu; Hongjie, Fan

    2017-01-06

    Swine streptococcosis is a significant threat to the Chinese pig industry, and Streptococcus equi ssp. zooepidemicus (SEZ) is one of the major pathogens. SEZ ATCC35246 is a classical virulent strain, while SEZ ST171 is a Chinese attenuated vaccine strain. In this study, we employed stable isotope labeling by amino acids in cell culture and liquid chromatography-mass spectrometry (LC-MS) to determine the differential response of macrophages to infection by these two strains. Eighty-seven upregulated proteins and 135 downregulated proteins were identified. The proteomic results were verified by real-time polymerase chain reaction for 10 chosen genes and Western blotting for three proteins. All differentially abundant proteins were analyzed for their Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations. Certain downregulated proteins were associated with immunity functions, and the upregulated proteins were related to cytomembrane and cytoskeleton regulation. The phagocytosis rate and cytokine genes transcription in Raw264.7 cells during SEZ ATCC35246 and ST171 infection were detected to confirm the bioinformatics results. These results showed that different effects on macrophage phagocytosis and cytokine expression might explain the different phenotypes of SEZ ATCC35246 and ST171 infection. This research provided clues to the mechanisms of host immunity responses to SEZ ST171and SEZ ATCC35246, which could identify potential therapy and vaccine development targets.

  17. Selecting vaccine strains for H3N2 human influenza A virus.

    PubMed

    Suzuki, Yoshiyuki

    2015-06-01

    H3N2 human influenza A virus causes epidemics of influenza mainly in the winter season in temperate regions. Since the antigenicity of this virus evolves rapidly, several attempts have been made to predict the major amino acid sequence of hemagglutinin 1 (HA1) in the target season of vaccination. However, the usefulness of predicted sequence was unclear because its relationship to the antigenicity was unknown. Here the antigenic model for estimating the degree of antigenic difference (antigenic distance) between amino acid sequences of HA1 was integrated into the process of selecting vaccine strains for H3N2 human influenza A virus. When the effectiveness of a potential vaccine strain for a target season was evaluated retrospectively using the average antigenic distance between the strain and the epidemic viruses sampled in the target season, the most effective vaccine strain was identified mostly in the season one year before the target season (pre-target season). Effectiveness of actual vaccines appeared to be lower than that of the strains randomly chosen in the pre-target season on average. It was recommended to replace the vaccine strain for every target season with the strain having the smallest average antigenic distance to the others in the pre-target season. The procedure of selecting vaccine strains for future epidemic seasons described in the present study was implemented in the influenza virus forecasting system (INFLUCAST) (http://www.nsc.nagoya-cu.ac.jp/~yossuzuk/influcast.html).

  18. A comparison of monovalent Hong Kong influenza virus vaccine with vaccines containing only pre-1968 Asian strains in adult volunteers

    PubMed Central

    Hobson, D.; Baker, F. A.; Chivers, C. P.; Reed, Sylvia E.; Sharp, D.

    1970-01-01

    A total of 1601 adult industrial workers were vaccinated with either monovalent inactivated vaccine of the Hong Kong strain of influenza A virus, or with polyvalent vaccine containing only pre-1968 Asian viruses. Serological investigations on a random sample of volunteers showed that 53/56 (95%) given Hong Kong vaccine developed a significant rise in specific haemagglutination-inhibiting antibody; final titres were 1/48 or greater in 39 (70%) and the GMT (geometric mean titre) was 96·5. After polyvalent Asian vaccine, 40/67 (60%) also produced antibody against Hong Kong virus, but only 21 (31%) had final titres of 1/48 or above, and the GMT rose only to 14·1. An intranasal spray of the Hong Kong vaccine in addition to injected Asian vaccine gave no additional increase in antibody. Each type of vaccine stimulated a recall of pre-existing antibody against Asian viruses. The possible significance of heterologous responses to the two vaccines is discussed. The incidence of clinical influenza in the trial population was sporadic, and the infection rates were too low to allow any accurate estimate of the protective efficiency of the two vaccines. PMID:4917915

  19. Oral vaccination against mycoplasmal pneumonia of swine using a live Erysipelothrix rhusiopathiae vaccine strain as a vector.

    PubMed

    Ogawa, Yohsuke; Oishi, Eiji; Muneta, Yoshihiro; Sano, Akiyuki; Hikono, Hirokazu; Shibahara, Tomoyuki; Yagi, Yukio; Shimoji, Yoshihiro

    2009-07-16

    Erysipelothrix rhusiopathiae Koganei 65-0.15 strain, the live swine erysipelas vaccine for subcutaneous injection, has been shown to colonize the tonsils of pigs after oral inoculation. We thus evaluated the possible use of the strain as a vector for oral vaccination against mycoplasmal pneumonia of swine. Recombinant E. rhusiopathiae strains expressing the C-terminal domain of the P97 adhesin of Mycoplasma hyopneumoniae were constructed and examined for vaccine efficacy in mice and pigs. Mice subcutaneously inoculated with the recombinant strains were protected from challenge exposure to a virulent E. rhusiopathiae. Administration of milk replacer containing recombinant E. rhusiopathiae expressing the M. hyopneumoniae protein protected pigs from death after exposure to E. rhusiopathiae and significantly reduced the severity of pneumonic lung lesions caused by infection with M. hyopneumoniae.

  20. Experimental Infection of Horses with an Attenuated Venezuelan Equine Encephalomyelitis Vaccine (Strain TC-83)

    PubMed Central

    Walton, Thomas E.; Alvarez, Otto; Buckwalter, Ross M.; Johnson, Karl M.

    1972-01-01

    Ten horses (Equus caballus) were vaccinated with strain TC-83 Venezuelan equine encephalomyelitis (VEE) virus vaccine. Febrile responses and leukopenia due to a reduction of lymphocytes and neutrophils were observed in all animals. Viremias were demonstrable in eight horses, with a maximum of 103.5 median tissue culture infectious dose units per ml of serum in two horses. Clinical illness with depression and anorexia were observed in five horses. Neutralizing (N), hemagglutination-inhibiting, and complement-fixing antibodies to the vaccine virus were demonstrable by 5, 6.5, and 7 days, respectively, after vaccination. Differential titrations of serum to six VEE strains revealed high titers of N antibody to vaccine virus, moderate titers to the epizootic Trinidad donkey no. 1 strain (VEE antigenic subtype I, variant A) from which TC-83 was derived, and low titers to two other epizootic strains (subtype I, variants B and C) in all horses at 1 month after vaccination; some animals responded with low levels of N antibody to the enzootic viruses (subtype I, variants D and E). Fourteen months after vaccination, six animals with detectable N antibody were challenged with MF-8 (subtype I, variant B), an epidemic-epizootic strain isolated in 1969 from a man in Honduras. All horses resisted challenge with the equine pathogenic strain of VEE. Marked increases of N antibody in most horses were demonstrable to some VEE strains when tested 1 month after challenge. PMID:4637604

  1. Genetic characterisation of attenuated SAD rabies virus strains used for oral vaccination of wildlife.

    PubMed

    Geue, Lutz; Schares, Susann; Schnick, Christina; Kliemt, Jeannette; Beckert, Aline; Freuling, Conrad; Conraths, Franz J; Hoffmann, Bernd; Zanoni, Reto; Marston, Denise; McElhinney, Lorraine; Johnson, Nicholas; Fooks, Anthony R; Tordo, Noel; Müller, Thomas

    2008-06-19

    The elimination of rabies from the red fox (Vulpes vulpes) in Western Europe has been achieved by the oral rabies vaccination (ORV) of wildlife with a range of attenuated rabies virus strains. With the exception of the vaccinia rabies glycoprotein recombinant vaccine (VRG), all strains were originally derived from a common ancestor; the Street Alabama Dufferin (SAD) field strain. However, after more than 30 years of ORV it is still not possible to distinguish these vaccine strains and there is little information on the genetic basis for their attenuation. We therefore sequenced and compared the full-length genome of five commercially available SAD vaccine viruses (SAD B19, SAD P5/88, SAG2, SAD VA1 and SAD Bern) and four other SAD strains (the original SAD Bern, SAD VA1, ERA and SAD 1-3670 Wistar). Nucleotide sequencing allowed identifying each vaccine strain unambiguously. Phylogenetic analysis revealed that the majority of the currently used commercial attenuated rabies virus vaccines appear to be derived from SAD B19 rather than from SAD Bern. One commercially available vaccine virus did not contain the SAD strain mentioned in the product information of the producer. Two SAD vaccine strains appeared to consist of mixed genomic sequences. Furthermore, in-del events targeting A-rich sequences (in positive strand) within the 3' non-coding regions of M and G genes were observed in SAD-derivates developed in Europe. Our data also supports the idea of a possible recombination that had occurred during the derivation of the European branch of SAD viruses. If confirmed, this recombination event would be the first one reported among RABV vaccine strains.

  2. Lights and shades on an historical vaccine canine distemper virus, the Rockborn strain.

    PubMed

    Martella, V; Blixenkrone-Møller, M; Elia, G; Lucente, M S; Cirone, F; Decaro, N; Nielsen, L; Bányai, K; Carmichael, L E; Buonavoglia, C

    2011-02-01

    Both egg- and cell-adapted canine distemper virus (CDV) vaccines are suspected to retain residual virulence, especially if administered to immuno-suppressed animals, very young pups or to highly susceptible animal species. In the early 1980s, post-vaccine encephalitis was reported in dogs from various parts of Britain after administration of a particular batch of combined CDV Rockborn strain/canine adenovirus type-1 vaccine, although incrimination of the Rockborn strain was subsequently retracted. Notwithstanding, this, and other reports, led to the view that the Rockborn strain is less attenuated and less safe than other CDV vaccines, and the Rockborn strain was officially withdrawn from the markets in the mid 1990s. By sequencing the H gene of the strain Rockborn from the 46th laboratory passage, and a commercial vaccine (Candur(®) SH+P, Hoechst Rousell Vet GmbH), the virus was found to differ from the commonly used vaccine strain, Onderstepoort (93.0% nt and 91.7% aa), and to resemble more closely (99.6% nt and 99.3% aa) a CDV strain detected in China from a Lesser Panda (Ailurus fulgens). An additional four CDV strains matching (>99% nt identity) the Rockborn virus were identified in the sequence databases. Also, Rockborn-like strains were identified in two vaccines currently in the market. These findings indicate that Rockborn-like viruses may be recovered from dogs or other carnivores with distemper, suggesting cases of residual virulence of vaccines, or circulation of vaccine-derived Rockborn-like viruses in the field.

  3. Optimization and Characterization of Candidate Strain for Coxsackievirus A16 Inactivated Vaccine

    PubMed Central

    Li, Jingliang; Liu, Guanchen; Liu, Xin; Yang, Jiaxin; Chang, Junliang; Zhang, Wenyan; Yu, Xiao-Fang

    2015-01-01

    Coxsackievirus A16 (CA16) and enterovirus 71 (EV71), both of which can cause hand, foot and mouth disease (HFMD), are responsible for large epidemics in Asian and Pacific areas. Although inactivated EV71 vaccines have completed testing in phase III clinical trials in Mainland China, CA16 vaccines are still under development. A Vero cell-based inactivated CA16 vaccine was developed by our group. Screening identified a CA16 vaccine strain (CC024) isolated from HFMD patients, which had broad cross-protective abilities and satisfied all requirements for vaccine production. Identification of the biological characteristics showed that the CA16CC024 strain had the highest titer (107.5 CCID50/mL) in Vero cells, which would benefit the development of an EV71/CA16 divalent vaccine. A potential vaccine manufacturing process was established, including the selection of optimal time for virus harvesting, membrane for diafiltration and concentration, gel-filtration chromatography for the down-stream virus purification and virus inactivation method. Altogether, the analyses suggested that the CC-16, a limiting dilution clone of the CC024 strain, with good genetic stability, high titer and broad-spectrum immunogenicity, would be the best candidate strain for a CA16 inactivated vaccine. Therefore, our study provides valuable information for the development of a Vero cell-based CA16 or EV71-CA16 divalent inactivated vaccine. PMID:26193302

  4. Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges

    SciTech Connect

    Wang Danher; Hevey, Michael; Juompan, Laure Y.; Trubey, Charles M.; Raja, Nicholas U.; Deitz, Stephen B.; Woraratanadharm, Jan; Luo Min; Yu Hong; Swain, Benjamin M.; Moore, Kevin M.; Dong, John Y. . E-mail: dongj@genphar.com

    2006-09-30

    The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guinea pigs. Significantly, guinea pigs vaccinated with at least 5 x 10{sup 7} pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV.

  5. Challenges of selecting seasonal influenza vaccine strains for humans with diverse pre-exposure histories

    PubMed Central

    Hensley, Scott E.

    2014-01-01

    Seasonal influenza vaccine strains are routinely updated when influenza viruses acquire mutations in exposed regions of the hemagglutinin and neuraminidase glycoproteins. Ironically, although thousands of viral isolates are sequenced each year, today's influenza surveillance community places less emphasis on viral genetic information and more emphasis on classical serological assays when choosing vaccine strains. Here, I argue that these classical serological assays are oversimplified and that they fail to detect influenza mutations that facilitate escape of particular types of human antibodies. I propose that influenza vaccine strains should be updated more frequently even when classical serological assays fail to detect significant antigenic alterations. PMID:25108824

  6. Challenges of selecting seasonal influenza vaccine strains for humans with diverse pre-exposure histories.

    PubMed

    Hensley, Scott E

    2014-10-01

    Seasonal influenza vaccine strains are routinely updated when influenza viruses acquire mutations in exposed regions of the hemagglutinin and neuraminidase glycoproteins. Ironically, although thousands of viral isolates are sequenced each year, today's influenza surveillance community places less emphasis on viral genetic information and more emphasis on classical serological assays when choosing vaccine strains. Here, I argue that these classical serological assays are oversimplified and that they fail to detect influenza mutations that facilitate escape of particular types of human antibodies. I propose that influenza vaccine strains should be updated more frequently even when classical serological assays fail to detect significant antigenic alterations. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Genotype characterization of commonly used Newcastle disease virus vaccine strains of India.

    PubMed

    Dey, Sohini; Chellappa, Madhan Mohan; Gaikwad, Satish; Kataria, Jag Mohan; Vakharia, Vikram N

    2014-01-01

    Newcastle disease is an avian pathogen causing severe economic losses to the Indian poultry industry due to recurring outbreaks in vaccinated and unvaccinated flocks. India being an endemic country, advocates vaccination against the virus using lentogenic and mesogenic strains. Two virus strains which are commonly used for vaccination are strain F (a lentogenic virus) and strain R2B (a mesogenic virus). Strain F is given to 0-7 days old chicks and R2B is given to older birds which are around 6-8 weeks old. To understand the genetic makeup of these two strains, a complete genome study and phylogenetic analysis of the F, HN genes of these vaccine strains were carried out. Both the viral strains had a genome length of 15,186 nucleotides and consisted of six genes with conserved complimentary 3' leader and 5' trailer regions. The fusion protein cleavage site of strain F is GGRQGRL and strain R2B is RRQKRF. Although both the viral strains had different virulence attributes, the length of the HN protein was similar with 577 amino acids. Phylogenetic analysis of F, HN and complete genome sequences grouped these two strains in genotype II category which are considered as early genotypes and corroborated with their years of isolation.

  8. Field study of vaccination of cattle with Brucella abortus strains RB51 and 19 under high and low disease prevalence.

    PubMed

    Lord, V R; Schurig, G G; Cherwonogrodzky, J W; Marcano, M J; Melendez, G E

    1998-08-01

    To assess humoral and protective immunity in cattle vaccinated by 12 months with Brucella abortus vaccine strains RB51 and 19 under field conditions of high and low brucellosis prevalence. 450 seronegative female cattle: 330 three to eight months old (calves), and 120 ten to twelve months old (heifers). Ranch A had high prevalence (39%) of brucellosis, and ranch B had low prevalence (2%), as determined by results of conventional serologic testing: agar gel immunodiffusion and the ring test. Seronegative cattle were vaccinated once or twice with 5 x 10(9) colony-forming units of B abortus strain RB51 or once with strain 19. After vaccinating 285 cattle with strain RB51 and 165 with strain 19, 74 (26%) and 30 (18%), respectively, were bred to seropositive bulls, then were kept within the infected herd of origin. All cattle vaccinated with strain 19 seroconverted 30 days later. All 285 cattle vaccinated with strain RB51 had negative results for all serologic tests, including agar gel immunodiffusion. All RB51-vaccinated cattle that became pregnant had negative results for the ring test and for conventional serologic tests after their first calving. Strain RB51 can be used as a live organism vaccine without inducing antibody titers that interfere with serodiagnosis, and induced 100% protection against field strain B abortus-induced abortion in cattle vaccinated at least 1 year before mating to an infected bull. Vaccination with strain 19 under similar conditions was less effective than vaccination with strain RB51.

  9. Divergence, not diversity of an attenuated equine lentivirus vaccine strain correlates with protection from disease.

    PubMed

    Craigo, Jodi K; Barnes, Shannon; Cook, Sheila J; Issel, Charles J; Montelaro, Ronald C

    2010-11-29

    We recently reported an attenuated EIAV vaccine study that directly examined the effect of lentiviral envelope sequence variation on vaccine efficacy. The study [1] demonstrated for the first time the failure of an ancestral vaccine to protect and revealed a significant, inverse, linear relationship between envelope divergence and protection from disease. In the current study we examine in detail the evolution of the attenuated vaccine strain utilized in this previous study. We demonstrate here that the attenuated strain progressively evolved during the six-month pre-challenge period and that the observed protection from disease was significantly associated with divergence from the original vaccine strain. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Effects of Vaccination with the C-Strain Vaccine on Immune Cells and Cytokines of Pigs Against Classical Swine Fever Virus.

    PubMed

    Xu, Lu; Fan, Xue-Zheng; Zhao, Qi-Zu; Zhang, Zheng-Xing; Chen, Kai; Ning, Yi-Bao; Zhang, Qian-Yi; Zou, Xing-Qi; Zhu, Yuan-Yuan; Li, Cui; Zhang, Yu-Jie; Wang, Qin

    2017-05-17

    The attenuated C-strain vaccine against classical swine fever virus (CSFV) is one of the safest and most effective attenuated vaccines. However, little is known of the host immune response after vaccination with the C-strain vaccine. Blood samples from vaccinated pigs were collected to evaluate the number of immune cells, the level of specific CSFV antibody, and related cytokines induced by the vaccination of C-strain vaccine. The C-strain nucleic acid was gradually removed and specific antibody to vaccine kept increasing; the amount of the lymphocyte, Tc cell, and Th cell increased; some inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor-α mainly showed downregulated trends, but IL-6 and IL-8 were upregulated greatly; IL-2, IL-4, IL-5, IL-12p40, IL-13, interferon (IFN)-I, and Toll-like receptors (TLRs) kept high expression level after 28 days postvaccination (dpv); IFN-γ was upregulated slightly at 5 and 9 dpv, respectively. These results suggest that the C-strain vaccine induces a Th2 cell response to produce the specific antibody. The vaccine virus replicates at very low level. C-strain vaccine burden has close relationship with the expression of TLRs. The overexpression of TLRs initiates the innate immune system to clear up the vaccine. Meanwhile, ILs expressed by immune system induce the differentiation of B cells and produce specific antibody.

  11. Salmonella Gallinarum field isolates from laying hens are related to the vaccine strain SG9R.

    PubMed

    Van Immerseel, F; Studholme, D J; Eeckhaut, V; Heyndrickx, M; Dewulf, J; Dewaele, I; Van Hoorebeke, S; Haesebrouck, F; Van Meirhaeghe, H; Ducatelle, R; Paszkiewicz, K; Titball, R W

    2013-10-09

    Salmonella enterica subspecies enterica serotype Gallinarum can cause severe systemic disease in chickens and a live Salmonella Gallinarum 9R vaccine (SG9R) has been used widely to control disease. Using whole-genome sequencing we found point mutations in the pyruvate dehydrogenase (aceE) and/or lipopolysaccharide 1,2-glucosyltransferase (rfaJ) genes that likely explain the attenuation of the SG9R vaccine strain. Molecular typing using Pulsed Field Gel Electrophoresis and Multiple-Locus Variable number of tandem repeat Analysis showed that strains isolated from different layer flocks in multiple countries and the SG9R vaccine strain were similar. The genome of one Salmonella Gallinarum field strain, isolated from a flock with a mortality peak and selected on the basis of identical PFGE and MLVA patterns with SG9R, was sequenced. We found 9 non-silent single-nucleotide differences distinguishing the field strain from the SG9R vaccine strain. Our data show that a Salmonella Gallinarum field strain isolated from laying hens is almost identical to the SG9R vaccine. Mutations in the aceE and rfaJ genes could explain the reversion to a more virulent phenotype. Our results highlight the importance of using well defined gene deletion mutants as vaccines.

  12. Immune responses of bison and efficacy after booster vaccination with Brucella abortus strain RB51.

    PubMed

    Olsen, S C; McGill, J L; Sacco, R E; Hennager, S G

    2015-04-01

    Thirty-one bison heifers were randomly assigned to receive saline or a single vaccination with 10(10) CFU of Brucella abortus strain RB51. Some vaccinated bison were randomly selected for booster vaccination with RB51 at 11 months after the initial vaccination. Mean antibody responses to RB51 were greater (P < 0.05) in vaccinated bison after initial and booster vaccination than in nonvaccinated bison. The proliferative responses by peripheral blood mononuclear cells (PBMC) from the vaccinated bison were greater (P < 0.05) than those in the nonvaccinated bison at 16 and 24 weeks after the initial vaccination but not after the booster vaccination. The relative gene expression of gamma interferon (IFN-γ) was increased (P < 0.05) in the RB51-vaccinated bison at 8, 16, and 24 weeks after the initial vaccination and at 8 weeks after the booster vaccination. The vaccinated bison had greater (P < 0.05) in vitro production of IFN-γ at all sampling times, greater interleukin-1β (IL-1β) production in various samplings after the initial and booster vaccinations, and greater IL-6 production at one sampling time after the booster vaccination. Between 170 and 180 days of gestation, the bison were intraconjunctivally challenged with approximately 1 × 10(7) CFU of B. abortus strain 2308. The incidences of abortion and infection were greater (P < 0.05) in the nonvaccinated bison after experimental challenge than in the bison receiving either vaccination treatment. Booster-vaccinated, but not single-vaccinated bison, had a reduced (P < 0.05) incidence of infection in fetal tissues and maternal tissues compared to that in the controls. Compared to the nonvaccinated bison, both vaccination treatments lowered the colonization (measured as the CFU/g of tissue) of Brucella organisms in all tissues, except in retropharyngeal and supramammary lymph nodes. Our study suggests that RB51 booster vaccination is an effective vaccination strategy for enhancing herd immunity against

  13. Safety and immunogenicity of Brucella abortus strain RB51 vaccine in cross bred cattle calves in India.

    PubMed

    Singh, Rashmi; Basera, Sanjay Singh; Tewari, Kamal; Yadav, Shweta; Joshi, Sumit; Singh, Brajesh; Mukherjee, Falguni

    2012-03-01

    Safety and immunogenicity of Brucella abortus RB51 vaccine has been evaluated in an organised dairy farm in India. All the cattle (r = 29) vaccinated with strain RB51 'responded' to the vaccine as demonstrated by iELISA using acetone killed strain RB51 antigen. The percentage responders at day 35, 60 and 90 post vaccination were 100%, 95% and 20%, respectively. Strain RB51 was able to elicit a good IFN-gamma response from vaccinated animals. The post-vaccination time point analysis indicated that the cumulative IFN-gamma response of whole blood from vaccinates stimulated with heat killed RB51 antigen was elicited in 80% of calves at 60 days post vaccination. Absence of strain RB51 in the secretions and excretion and lack of local or systemic reaction indicated the safety of the vaccine.

  14. Vaccine-strain herpes zoster found in the trigeminal nerve area in a healthy child: A case report.

    PubMed

    Iwasaki, Sayaka; Motokura, Kouji; Honda, Yoshitaka; Mikami, Masamitsu; Hata, Daisuke; Hata, Atsuko

    2016-12-01

    A previously healthy 2-year-old girl, vaccinated for varicella at 17 months, was admitted because of left-sided facial herpes zoster caused by vaccine-strain varicella-zoster virus (VZV). She recovered fully with no complication after intravenous treatment using acyclovir. Earlier reports have described that herpes zoster (HZ) rashes caused by vaccine-strain VZV tend to occur on the dermis corresponding to the skin area where the varicella vaccine was received. However, rashes appeared on this girl only in the trigeminal nerve area, which is unrelated to the vaccinated site. Results underscore the importance of distinguishing vaccine-strain VZV from wild-type VZV whenever encountering HZ cases after vaccination, even in immunocompetent children, irrespective of the skin lesion site. Monitoring vaccine-strain HZ incidence rates is expected to elucidate many aspects of varicella vaccine safety.

  15. Genome sequence of SG33 strain and recombination between wild-type and vaccine myxoma viruses.

    PubMed

    Camus-Bouclainville, Christelle; Gretillat, Magalie; Py, Robert; Gelfi, Jacqueline; Guérin, Jean Luc; Bertagnoli, Stéphane

    2011-04-01

    Myxomatosis in Europe is the result of the release of a South America strain of myxoma virus in 1952. Several attenuated strains with origins in South America or California have since been used as vaccines in the rabbit industry. We sequenced the genome of the SG33 myxoma virus vaccine strain and compared it with those of other myxoma virus strains. We show that SG33 genome carries a large deletion in its right end. Furthermore, our data strongly suggest that the virus isolate from which SG33 is derived results from an in vivo recombination between a wild-type South America (Lausanne) strain and a California MSD-derived strain. These findings raise questions about the use of insufficiently attenuated virus in vaccination.

  16. Fatal varicella due to the vaccine-strain varicella-zoster virus

    PubMed Central

    Leung, Jessica; Siegel, Subhadra; Jones, James F; Schulte, Cynthia; Blog, Debra; Scott Schmid, D; Bialek, Stephanie R; Marin, Mona

    2014-01-01

    We describe a death in a 15-mo-old girl who developed a varicella-like rash 20 d after varicella vaccination that lasted for 2 mo despite acyclovir treatment. The rash was confirmed to be due to vaccine-strain varicella-zoster virus (VZV). This is the first case of fatal varicella due to vaccine-strain VZV reported from the United States. The patient developed severe respiratory complications that worsened with each new crop of varicella lesions; vaccine-strain VZV was detected in the bronchial lavage specimen. Sepsis and multi-organ failure led to death. The patient did not have a previously diagnosed primary immune deficiency, but her failure to thrive and repeated hospitalizations early in life (starting at 5 mo) for presumed infections and respiratory compromise treated with corticosteroids were suggestive of a primary or acquired immune deficiency. Providers should monitor for adverse reactions after varicella vaccination. If severe adverse events develop, acyclovir should be administered as soon as possible. The possibility of acyclovir resistance and use of foscarnet should be considered if lesions do not improve after 10 d of treatment (or if they become atypical [e.g., verrucous]). Experience with use of varicella vaccine indicates that the vaccine has an excellent safety profile and that serious adverse events are very rare and mostly described in immunocompromised patients. The benefit of vaccination in preventing severe disease and mortality outweigh the low risk of severe events occurring after vaccination. PMID:23982221

  17. Application of reverse genetics for producing attenuated vaccine strains against highly pathogenic avian influenza viruses.

    PubMed

    Uchida, Yuko; Takemae, Nobuhiro; Saito, Takehiko

    2014-08-01

    In this study, reverse genetics was applied to produce vaccine candidate strains against highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype. The H5 subtype vaccine strains were generated by a reverse genetics method in a biosafety level 2 facility. The strain contained the HA gene from the H5N1 subtype HPAIV attenuated by genetic modification at the cleavage site, the NA gene derived from the H5N1 subtype HPAI or the H5N3 subtype of avian influenza virus and internal genes from A/Puerto Rico/8/34. Vaccination with an inactivated recombinant virus with oil-emulsion completely protected chickens from a homologous viral challenge with a 640 HAU or 3,200 HAU/vaccination dose. Vaccination with a higher dose of antigen, 3,200 HAU, was effective at increasing survival and efficiently reduced viral shedding even when challenged by a virus of a different HA clade. The feasibility of differentiation of infected from vaccinated animals (DIVA) was demonstrated against a challenge with H5N1 HPAIVs when the recombinant H5N3 subtype viruses were used as the antigens of the vaccine. Our study demonstrated that the use of reverse genetics would be an option to promptly produce an inactivated vaccine with better matching of antigenicity to a circulating strain.

  18. Complete Genome Sequences of Four Bordetella pertussis Vaccine Reference Strains from Serum Institute of India

    PubMed Central

    Peng, Yanhui; Loparev, Vladimir; Johnson, Taccara; Juieng, Phalasy; Gairola, Sunil; Kumar, Rakesh; Shaligram, Umesh; Gowrishankar, Ramnath; Moura, Hercules; Rees, Jon; Schieltz, David M.; Williamson, Yulanda; Woolfitt, Adrian; Barr, John; Tondella, M. Lucia; Williams, Margaret M.

    2016-01-01

    Serum Institute of India is among the world’s largest vaccine producers. Here, we report the complete genome sequences for four Bordetella pertussis strains used by Serum Institute of India in the production of whole-cell pertussis vaccines. PMID:28007855

  19. Experimental studies with homologous subtype vaccines produced with multiple antigenically different seed strains

    USDA-ARS?s Scientific Manuscript database

    Due to the high antigenic variability of avian influenza virus, vaccines need to be continually updated to maintain adequate protection to evolving field strains. One possible approach, to mitigating the effects of antigenic change, is to use vaccines containing more than one isolate of the same su...

  20. In vitro permissivity of bovine cells for wild-type and vaccinal myxoma virus strains.

    PubMed

    Pignolet, Béatrice; Duteyrat, Jean-Luc; Allemandou, Aude; Gelfi, Jacqueline; Foucras, Gilles; Bertagnoli, Stéphane

    2007-09-27

    Myxoma virus (MYXV), a leporide-specific poxvirus, represents an attractive candidate for the generation of safe, non-replicative vaccine vector for non-host species. However, there is very little information concerning infection of non-laboratory animals species cells with MYXV. In this study, we investigated interactions between bovine cells and respectively a wild type strain (T1) and a vaccinal strain (SG33) of MYXV. We showed that bovine KOP-R, BT and MDBK cell lines do not support MYXV production. Electron microscopy observations of BT-infected cells revealed the low efficiency of viral entry and the production of defective virions. In addition, infection of bovine peripheral blood mononuclear cells (PBMC) occurred at a very low level, even following non-specific activation, and was always abortive. We did not observe significant differences between the wild type strain and the vaccinal strain of MYXV, indicating that SG33 could be used for new bovine vaccination strategies.

  1. Genomic variations associated with attenuation in Mycobacterium avium subsp. paratuberculosis vaccine strains

    PubMed Central

    2013-01-01

    Background Mycobacterium avium subspecies paratuberculosis (MAP) whole cell vaccines have been widely used tools in the control of Johne’s disease in animals despite being unable to provide complete protection. Current vaccine strains derive from stocks created many decades ago; however their genotypes, underlying mechanisms and relative degree of their attenuation are largely unknown. Results Using mouse virulence studies we confirm that MAP vaccine strains 316 F, II and 2e have diverse but clearly attenuated survival and persistence characteristics compared with wild type strains. Using a pan genomic microarray we characterise the genomic variations in a panel of vaccine strains sourced from stocks spanning over 40 years of maintenance. We describe multiple genomic variations specific for individual vaccine stocks in both deletion (26–32 Kbp) and tandem duplicated (11–40 Kbp) large variable genomic islands and insertion sequence copy numbers. We show individual differences suitable for diagnostic differentiation between vaccine and wild type genotypes and provide evidence for functionality of some of the deleted MAP-specific genes and their possible relation to attenuation. Conclusions This study shows how culture environments have influenced MAP genome diversity resulting in large tandem genomic duplications, deletions and transposable element activity. In combination with classical selective systematic subculture this has led to fixation of specific MAP genomic alterations in some vaccine strain lineages which link the resulting attenuated phenotypes with deficiencies in high reactive oxygen species handling. PMID:23339684

  2. Biosafety aspects of the recombinant live oral Vibrio cholerae vaccine strain CVD 103-HgR.

    PubMed

    Viret, Jean-François; Dietrich, Guido; Favre, Didier

    2004-06-23

    The development of live attenuated vaccines, allowing for the safe and effective immunisation at mucosal surfaces, is a strategy of great interest for vaccinologists. The main advantage of this approach over conventional parenteral vaccines is the induction of strong mucosal immune responses, allowing targeting of the pathogen at the initial point of contact with the host. Further advantages include the ease of administration, high acceptance by vaccines, and relatively low production costs. Finally, well-characterised, safe and immunogenic vaccine strains are well suited as vectors for the mucosal delivery of foreign vaccine antigens and of DNA vaccines. However, such vaccines, when based on or containing genetically modified organisms (GMOs), are facing new and specific regulatory hurdles, particularly regarding the potential risks for humans and the environment. In this contribution we address selected aspects of the risk assessment of live attenuated bacterial vaccines covered in the course of the registration of vaccine strain CVD 103-HgR as a recombinant live oral vaccine against cholera.

  3. Identification of in vitro upregulated genes in a modified live vaccine strain of Edwardsiella ictaluri compared to a virulent parent strain

    USDA-ARS?s Scientific Manuscript database

    Using PCR-select subtractive cDNA hybridization technique, 41 expressed sequence tags (ESTs) were isolated from a modified live vaccine strain (AQUAVAC-ESC©, formerly RE-33) vs a virulent parent strain (EILO) of Edwardsiella ictaluri. Transcriptional levels of the 41 ESTs in the vaccine strain and t...

  4. [Construction of hpaA gene-engineered attenuated Salmonella typhimurium vaccine strain].

    PubMed

    Zhu, Senlin; Chen, Minhu; Chen, Jie; Hu, Pinjin; Li, Guoqing

    2002-02-01

    To express Helicobacter pylori hpaA gene in attenuated Salmonella typhimurium vaccine vehicle, and elucidate the potential value of attenuated Salmonella typhimurium as a vector expressing Helicobacter pylori antigens, by means of molecular biology, 783 bp hpaA gene was cloned into NcoI-SalI site of a procaryotic expression plasmid pTrc99A, and the recombinant plasmid was then used to transform an attenuated Salmonella typhimurium vaccine strain SL3261, and the positive clones were screened by PCR and restriction enzyme digestion. HpaA expression was analyzed by SDS-PAGE and Western blot. Two and 10 days after recombinant strain intragastric immunization, the C57BL/6 mice was sacrificed, and the spleen and terminal ileum was cultured for recombinant strain. The results showed that a recombinant procaryotic expression plasmid pTrc99A-hpaA was constructed, and the recombinant plasmid was then introduced into an attenuated Salmonella typhimurium vaccine strain SL3261 successfully. HpaA was expressed in the recombinant strains as a 30 kD protein, and also its immunogenicity was confirmed by Western blot. Recombinant strain was found in both spleen and terminal ileum of each mouse two and ten days after intragastric immunization. We concluded that a recombinant live attenuated Salmonella typhimurium vaccine strain expressing Helicobacter pylori hpaA gene was constructed and identified, and this work will help to develop oral recombinant live vaccine strains against Helicobacter pylori infection.

  5. [Attenuation of a strain of rinderpest virus: potential homologous live vaccine].

    PubMed

    Diallo, A; Taylor, W P; Lefèvre, P C; Provost, A

    1989-01-01

    Peste des petits ruminants (PPR) is a highly contagious disease of small ruminants frequently associated with severe mortality in these hosts. In countries where it occurs, PPR represents an important constraint to the improved productivity of sheep and goats. Until now the only way to combat this plague has been the use of heterologous rinderpest vaccine; all attempts to develop a homologous vaccine have ended in failure. The present communication describes the attenuation of the Nigerian strain PPRV Nig 75/1 by serial passage in Vero cells. The avirulent virus obtained has the same characteristics as Plowright and Ferris' rinderpest vaccine. The virus is advanced as a potential homologous vaccine against PPR.

  6. Mathematical model of tuberculosis transmission in a two-strain with vaccination

    NASA Astrophysics Data System (ADS)

    Nainggolan, J.; Supian, S.; Supriatna, A. K.; Anggriani, N.

    2014-02-01

    This paper deals with the mathematical analysis of the spread of tuberculosis with vaccination in a two-strain model. The vaccination reproduction ratio (Rrs) and equilibria quantities for the models are determined and stability of the solution is analyzed. We prove that if the vaccination reproduction ratio Rrs < 1 the disease free equilibrium is locally and asymptotically stable on the nonnegative orthant and if Rrs > 1 of the other equilibria is locally and asymptotically stable. At the end of this study, the numerical computation presented and it shows that vaccination and treatment capable to reduce the number of exposed and infected compartments.

  7. The Cross-Neutralizing Activity of Enterovirus 71 Subgenotype C4 Vaccines in Healthy Chinese Infants and Children

    PubMed Central

    Li, Jingxin; Wang, Yiping; Li, Yanping; Gao, Fan; Yang, Lisheng; Yao, Xin; Shao, Jie; Xia, Ningshao; Liang, Zhenglun; Wang, Junzhi

    2013-01-01

    Background EV71 is one of major etiologic causes of hand-foot-mouth disease (HFMD) and leads to severe neurological complications in young children and infants. Recently inactivated EV71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. However, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because RNA recombination is seen more frequently in EV71 epidemics. Methodology/Principal Findings In this post-hoc study, sera from a subset of 119 infants and children in two clinical trials of EV71 subgenotype C4 vaccines (ClinicalTrials.gov Identifier: NCT01313715 and NCT01273246), were detected for neutralizing antibody (NTAb) titres with sera from infected patients as controls. Cytopathogenic effect method was employed to test NTAb against EV71 subgenotype B4, B5, C2, C4 and C5, which were prominent epidemic strains worldwide over the past decade. To validate the accuracy of the results, ELISpot assay was employed in parallel to detect NTAb in all the post-vaccine sera. After two-dose vaccination, 49 out of 53 participants in initially seronegative group and 52 out of 53 participants in initially seropositive group showed less than 4-fold differences in NTAb titers against five EV71 strains, whereas corresponding values among sera from pediatric patients recovering from EV71-induced HFMD and subclinically infected participants were 8/8 and 41/43, respectively. The geometric mean titers of participants against five subgenotypes EV71 all grew significantly after vaccinations, irrespective of the baseline NTAb titer. The relative fold increase in antibody titers (NTAb-FI) against B4, B5, C2, and C5 displayed a positive correlation to the NTAb-FI against C4. Conclusions/Significance The results demonstrated broad cross-neutralizing activity induced by two C4 EV71 vaccines in healthy Chinese infants and children. However, the degree of induced cross-protective immunity, and

  8. The cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.

    PubMed

    Mao, Qunying; Cheng, Tong; Zhu, Fengcai; Li, Jingxin; Wang, Yiping; Li, Yanping; Gao, Fan; Yang, Lisheng; Yao, Xin; Shao, Jie; Xia, Ningshao; Liang, Zhenglun; Wang, Junzhi

    2013-01-01

    EV71 is one of major etiologic causes of hand-foot-mouth disease (HFMD) and leads to severe neurological complications in young children and infants. Recently inactivated EV71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. However, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because RNA recombination is seen more frequently in EV71 epidemics. In this post-hoc study, sera from a subset of 119 infants and children in two clinical trials of EV71 subgenotype C4 vaccines (ClinicalTrials.gov Identifier: NCT01313715 and NCT01273246), were detected for neutralizing antibody (NTAb) titres with sera from infected patients as controls. Cytopathogenic effect method was employed to test NTAb against EV71 subgenotype B4, B5, C2, C4 and C5, which were prominent epidemic strains worldwide over the past decade. To validate the accuracy of the results, ELISpot assay was employed in parallel to detect NTAb in all the post-vaccine sera. After two-dose vaccination, 49 out of 53 participants in initially seronegative group and 52 out of 53 participants in initially seropositive group showed less than 4-fold differences in NTAb titers against five EV71 strains, whereas corresponding values among sera from pediatric patients recovering from EV71-induced HFMD and subclinically infected participants were 8/8 and 41/43, respectively. The geometric mean titers of participants against five subgenotypes EV71 all grew significantly after vaccinations, irrespective of the baseline NTAb titer. The relative fold increase in antibody titers (NTAb-FI) against B4, B5, C2, and C5 displayed a positive correlation to the NTAb-FI against C4. The results demonstrated broad cross-neutralizing activity induced by two C4 EV71 vaccines in healthy Chinese infants and children. However, the degree of induced cross-protective immunity, and the potential escape evolution for EV71 still need to be monitored

  9. Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions.

    PubMed

    Hacker, Jill K

    2017-03-01

    Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735-743, 2017, https://doi.org/10.1128/JCM.01879-16) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases. Copyright © 2017 American Society for Microbiology.

  10. Progress towards Rapid Detection of Measles Vaccine Strains: a Tool To Inform Public Health Interventions

    PubMed Central

    2016-01-01

    ABSTRACT Rapid differentiation of vaccine from wild-type strains in suspect measles cases is a valuable epidemiological tool that informs the public health response to this highly infectious disease. Few public health laboratories sequence measles virus-positive specimens to determine genotype, and the vaccine-specific real-time reverse transcriptase PCR (rRT-PCR) assay described by F. Roy et al. (J. Clin. Microbiol. 55:735–743, 2017, https://doi.org/10.1128/JCM.01879-16) offers a rapid, easily adoptable method to identify measles vaccine strains in suspect cases. PMID:28003421

  11. Abortion and premature birth in cattle following vaccination with Brucella abortus strain RB51.

    PubMed

    Fluegel Dougherty, Amanda M; Cornish, Todd E; O'Toole, Donal; Boerger-Fields, Amy M; Henderson, Owen L; Mills, Ken W

    2013-09-01

    Brucella abortus RB51 is the vaccine strain currently licensed for immunizing cattle against brucellosis in the United States. Most cattle are vaccinated as heifer calves at 4-12 months of age. Adult cattle may be vaccinated in selected high-risk situations. Two herds of pregnant adult cattle in the brucellosis-endemic area of Wyoming were vaccinated with a standard label dose (1.0-3.4 × 10(10) organisms) of RB51. Reproductive losses in the vaccinated herds were 5.3% (herd A) and 0.6% (herd B) and included abortions, stillbirths, premature calves, and unbred cows (presumed early abortion). Brucella abortus was cultured from multiple tissues of aborted and premature calves (7/9), and from placenta. Isolates were identified as B. abortus strain RB51 by standard strain typing procedures and a species-specific polymerase chain reaction. Bronchopneumonia with intralesional bacteria and placentitis were observed microscopically. There was no evidence of involvement of other infectious or toxic causes of abortion. Producers, veterinarians, and laboratory staff should be alert to the risk of abortion when pregnant cattle are vaccinated with RB51, to potential human exposure, and to the importance of distinguishing field from vaccinal strains of B. abortus.

  12. Evaluation of an attenuated strain of Ehrlichia canis as a vaccine for canine monocytic ehrlichiosis.

    PubMed

    Rudoler, Nir; Baneth, Gad; Eyal, Osnat; van Straten, Michael; Harrus, Shimon

    2012-12-17

    Canine monocytic ehrlichiosis is an important tick-borne disease worldwide. No commercial vaccine for the disease is currently available and tick control is the main preventive measure against the disease. The aim of this study was to evaluate the potential of a multi-passaged attenuated strain of Ehrlichia canis to serve as a vaccine for canine monocytic ehrlichiosis, and to assess the use of azithromycin in the treatment of acute ehrlichiosis. Twelve beagle dogs were divided into 3 groups of 4 dogs. Groups 1 and 2 were inoculated (vaccinated) with an attenuated strain of E. canis (#611A) twice or once, respectively. The third group consisted of naïve dogs which served as controls. All 3 groups were challenged with a wild virulent strain of E. canis by administering infected dog-blood intravenously. Transient thrombocytopenia was the only hematological abnormality observed following inoculation of dogs with the attenuated strain. Challenge with the virulent strain resulted in severe disease in all 4 control dogs while only 3 of 8 vaccinated dogs presented mild transient fever. Furthermore, the mean blood rickettsial load was significantly higher in the control group (27-92-folds higher during days 14-19 post challenge with the wild the strain) as compared to the vaccinated dogs. The use of azithromycin was assessed as a therapeutic agent for the acute disease. Four days treatment resulted in further deterioration of the clinical condition of the dogs. Molecular comparison of 4 genes known to express immunoreactive proteins and virulence factors (p30, gp19, VirB4 and VirB9) between the attenuated strain and the challenge wild strain revealed no genetic differences between the strains. The results of this study indicate that the attenuated E. canis strain may serve as an effective and secure future vaccine for canine ehrlichiosis.

  13. Ability of Brucella abortus rough vaccine strains to elicit DC and innate immunity in lung using a murine respiratory model.

    PubMed

    Surendran, Naveen; Zimmerman, Kurt; Seleem, Mohamed N; Sriranganathan, Nammalwar; Boyle, Stephen M; Hiltbold, Elizabeth M; Lawler, Heather; Heid, Bettina; Witonsky, Sharon G

    2010-10-08

    Brucella abortus strains RB51 and RB51SOD are live attenuated vaccine strains which protect mice against virulent B. abortus strain 2308 intraperitoneal challenge. By comparison, limited information is available on how Brucella vaccines stimulate pulmonary immunity against respiratory infection, another route of exposure in humans. Therefore, in this study, we assessed the ability of intranasally delivered vaccine strains RB51 and RB51SOD to induce innate immunity. Based on parameters assessed, rough strain RB51 induces a better innate immune response in lung versus strain RB51SOD. Additional studies to further delineate strain RB51's ability to stimulate DC and adaptive immunity are warranted.

  14. A test of antigenicity for the selection of strains for inclusion in cholera vaccines

    PubMed Central

    Finkelstein, Richard A.; Pongpairojana, Smarn

    1968-01-01

    The antigenicity of a large number of cholera vibrio strains was compared, in groups of rabbits, by evaluating the serological responses to single limited doses of vaccines prepared from the strains. On the basis of these tests, it was possible to construct 2 quadrivalent (El Tor and classical, Inaba and Ogawa) vaccines which differed significantly in antigenicity for rabbits but which were indistinguishable in the “standard” mouse-protection test. The advisability of using a test of antigenicity for selection of strains and laboratory evaluation of vaccines is considered. Application of the proposed antigenicity test would depend on further comparisons of human response to vaccines which differ in antigenicity for the rabbit. ImagesFIG. 4 PMID:5303406

  15. Potential of a sequence-based antigenic distance measure to indicate equine influenza vaccine strain efficacy.

    PubMed

    Daly, Janet M; Elton, Debra

    2013-12-09

    The calculation of p(epitope) values, a sequence-based measure of antigenic distance between strains, was developed for human influenza. The potential to apply the p(epitope) value to equine influenza vaccine strain selection was assessed. There was a negative correlation between p(epitope) value and vaccine efficacy for pairs of vaccine and challenge strains used in cross-protection studies in ponies that just reached statistical significance (p=0.046) only if one pair of viruses was excluded from the analysis. Thus the p(epitope) value has potential to provide additional data to consider in the decision-making process for updating equine influenza vaccine strains. However, further work is required to define the epitopes of the equine H3N8 haemagglutinin protein recognised by equine antibodies, which could lead to refinement of the p(epitope) value calculation. Furthermore, other factors such as vaccine potency and virulence of circulating strains may also influence vaccine efficacy.

  16. The establishment of sub-strain specific WHO Reference Reagents for BCG vaccine

    PubMed Central

    Dagg, Belinda; Hockley, Jason; Rigsby, Peter; Ho, Mei M.

    2014-01-01

    As the latest addition to the sub-strain specific WHO Reference Reagents of BCG vaccine, an international collaborative study was completed to evaluate the suitability of a candidate BCG Moreau-RJ sub-strain as a WHO Reference Reagent of BCG vaccine. This follows the recent replacement of the WHO 1st International Reference Preparation for BCG vaccine, by three sub-strain specific WHO Reference Reagents of BCG vaccine (Danish 1331, Tokyo 172-1 and Russian BCG-I) in order to complete the coverage of most predominant sub-strains used for BCG vaccine production and distribution for use worldwide. The study used cultural viable count and modified ATP assays to quantify the preparation and multiplex PCR to confirm the identity of the sub-strain. The establishment of this WHO Reference Reagent of BCG vaccine of Moreau-RJ sub-strain was approved by the WHO Expert Committee on Biological Standardization meeting in October 2012. This preparation is available for distribution by NIBSC-MHRA, UK. The data from real-time stability monitoring demonstrated that these Reference Reagents of BCG vaccine are very stable in storage condition at −20 °C. They serve as the valuable source of BCG Reference Reagents for use as comparators (1) for viability assays (such as cultural viable count and modified ATP assays); (2) for in vivo assays (such as the absence of virulent mycobacteria, dermal reactivity and protection assays) in the evaluation of candidate TB vaccines in non-clinical models; (3) for identity assays using molecular biology techniques. PMID:25312272

  17. Computational prediction of vaccine strains for human influenza A (H3N2) viruses.

    PubMed

    Steinbrück, L; Klingen, T R; McHardy, A C

    2014-10-01

    Human influenza A viruses are rapidly evolving pathogens that cause substantial morbidity and mortality in seasonal epidemics around the globe. To ensure continued protection, the strains used for the production of the seasonal influenza vaccine have to be regularly updated, which involves data collection and analysis by numerous experts worldwide. Computer-guided analysis is becoming increasingly important in this problem due to the vast amounts of generated data. We here describe a computational method for selecting a suitable strain for production of the human influenza A virus vaccine. It interprets available antigenic and genomic sequence data based on measures of antigenic novelty and rate of propagation of the viral strains throughout the population. For viral isolates sampled between 2002 and 2007, we used this method to predict the antigenic evolution of the H3N2 viruses in retrospective testing scenarios. When seasons were scored as true or false predictions, our method returned six true positives, three false negatives, eight true negatives, and one false positive, or 78% accuracy overall. In comparison to the recommendations by the WHO, we identified the correct antigenic variant once at the same time and twice one season ahead. Even though it cannot be ruled out that practical reasons such as lack of a sufficiently well-growing candidate strain may in some cases have prevented recommendation of the best-matching strain by the WHO, our computational decision procedure allows quantitative interpretation of the growing amounts of data and may help to match the vaccine better to predominating strains in seasonal influenza epidemics. Importance: Human influenza A viruses continuously change antigenically to circumvent the immune protection evoked by vaccination or previously circulating viral strains. To maintain vaccine protection and thereby reduce the mortality and morbidity caused by infections, regular updates of the vaccine strains are required. We

  18. Efficacy of single calfhood vaccination of elk with Brucella abortus strain 19

    USGS Publications Warehouse

    Roffe, T.J.; Jones, L.C.; Coffin, K.; Drew, M.L.; Sweeney, Steven J.; Hagius, S.D.; Elzer, P.H.; Davis, D.

    2004-01-01

    Brucellosis has been eradicated from cattle in the states of Wyoming, Montana, and Idaho, USA. However, free-ranging elk (Cervus elaphus) that use feedgrounds in the Greater Yellowstone Area (GYA) and bison (Bison bison) in Yellowstone and Grand Teton national parks still have high seroprevalence to the disease and have caused loss of brucellosis-free status in Wyoming. Management tools to control or eliminate the disease are limited; however, wildlife vaccination is among the methods currently used by wildlife managers in Wyoming. We conducted a controlled challenge study of single calfhood vaccination. Elk calves, caught in January and February of 1999 and 2000 and acclimated to captivity for 3 weeks, were randomly assigned to control or vaccinate groups. The vaccinate groups received Brucetta abortus vaccine strain 19 (S19) by hand-delivered intramuscular injection. Calves were raised to adulthood and bred at either 2.5 or 3.5 years of age for 2000 and 1999 captures, respectively. Eighty-nine (44 controls, 45 vaccinates) pregnant elk entered the challenge portion of the study. We challenged elk at mid-gestation with pathogenic B. abortus strain 2308 by intraconjunctival instillation. Abortion occurred in significantly more (P = 0.002) controls (42; 93%) than vaccinates (32; 71%), and vaccine protected 25% of the vaccinate group. We used Brucella culture of fetus/calf tissues to determine the efficacy of vaccination for preventing infection, and we found that the number of infected fetuses/calves did not differ between controls and vaccinates (P = 0.14). Based on these data, single calfhood vaccination with S19 has low efficacy, will likely have only little to moderate effect on Brucella prevalence in elk, and is unlikely to eradicate the disease in wildlife of the GYA.

  19. A comparative study of live attenuated F strain-derived Mycoplasma gallisepticum vaccines

    USDA-ARS?s Scientific Manuscript database

    Commercially available attenuated strains of Mycoplasma gallisepticum (MG) are commonly used within the layer industry to control MG-induced mycoplasmosis. Among these are two live MG vaccines derived from the moderately pathogenic MG “chick F” strain. In the present study, the commercially availa...

  20. Genome Sequence of the Soviet/Russian Bacillus anthracis Vaccine Strain 55-VNIIVViM

    PubMed Central

    Kotorashvili, Adam

    2016-01-01

    Bacillus anthracis strain 55-VNIIVViM is a live-attenuated nonencapsulated Soviet/Russian veterinary anthrax vaccine strain. We report here the genome of 55-VNIIVViM and confirm its phylogenetic placement in the global population structure of B. anthracis. PMID:28007853

  1. Complete Genome Sequence of the Attenuated Novobiocin-Resistant Streptococcus iniae Vaccine Strain ISNO

    PubMed Central

    Zhang, Dunhua; Zhang, Lee

    2014-01-01

    Streptococcus iniae ISNO is an attenuated novobiocin-resistant vaccine strain. Its full genome is 2,070,182 bp in length. The availability of this genome will allow comparative genomics to identify potential virulence genes important for pathogenesis of S. iniae and potential mechanisms associated with novobiocin resistance in this strain. PMID:24874684

  2. Draft Genome Sequence of Hypervirulent and Vaccine Candidate Streptococcus suis Strain SC19

    PubMed Central

    Teng, Lin; Dong, Xingxing; Zhou, Yang; Li, Zhiwei; Deng, Limei; Chen, Huanchun; Wang, Xiaohong

    2017-01-01

    ABSTRACT Streptococcus suis, a zoonotic bacterium found primarily in pigs, has been recognized recently as an emerging pathogen of humans. Herein, we describe the genome of Streptococcus suis strain SC19, a hypervirulent and vaccine candidate strain isolated from a pig amid the 2005 outbreak in China. PMID:28104658

  3. Identification of vaccine-derived rotavirus strains in children with acute gastroenteritis in Japan, 2012-2015.

    PubMed

    Kaneko, Mei; Takanashi, Sayaka; Thongprachum, Aksara; Hanaoka, Nozomu; Fujimoto, Tsuguto; Nagasawa, Koo; Kimura, Hirokazu; Okitsu, Shoko; Mizuguchi, Masashi; Ushijima, Hiroshi

    2017-01-01

    Two live attenuated oral rotavirus vaccines, Rotarix and RotaTeq, have been introduced as voluntary vaccination in Japan since 2011 and 2012, respectively. Effectiveness of the vaccines has been confirmed, whereas concerns such as shedding of the vaccine strains and gastroenteritis cases caused by vaccine strains are not well assessed. We aimed to identify the vaccine strains in children with acute gastroenteritis (AGE) to investigate the prevalence of AGE caused by vaccination or horizontal transmission of vaccine strains. A total of 1,824 stool samples were collected from children with AGE at six outpatient clinics in 2012-2015. Among all, 372 group A rotavirus (RVA) positive samples were screened for vaccine components by real-time RT-PCR which were designed to differentiate vaccine strains from rotavirus wild-type strains with high specificity. For samples possessing both vaccine and wild-type strains, analyses by next-generation sequencing (NGS) were conducted to characterize viruses existed in the intestine. As a result, Rotarix-derived strains were identified in 6 of 372 (1.6%) RVA positive samples whereas no RotaTeq strain was detected. Among six samples, four possessed Rotarix-derived strains while two possessed both Rotarix-derived strains and wild-type strains. In addition, other pathogens such as norovirus, enterovirus and E.coli were detected in four samples. The contribution of these vaccine strains to each patient's symptoms was unclear as all of the cases were vaccinated 2-14 days before sample collection. Proportion of average coverage for each segmented gene by NGS strongly suggested the concurrent infection of the vaccine-derived strain and the wild-type strain rather than reassortment of these two strains in one sample. This is the first study to report the prevalence of vaccine-derived strains in patients with RVA AGE in Japan as 1.6% without evidence of horizontal transmission. The results emphasized the importance of continuous monitoring on

  4. Anaplasma marginale Yucatan (Mexico) Strain. Assessment of low virulence and potential use as a live vaccine.

    PubMed

    Rodríguez Camarillo, Sergio D; García Ortiz, Miguel Angel; Rojas Ramírez, Edmundo E; Cantó Alarcón, Germinal J; Preciado de la Torre, Jesús F; Rosario Cruz, Rodrigo; Ramos Aragón, Juan A; Aboytes Torres, Ramón

    2008-12-01

    Anaplasma marginale Yucatan strain was found to have low virulence in cattle. We studied the virulence of this isolate by experimental inoculation of 113 susceptible cattle at increasing doses, after which only one animal required treatment for clinical disease. Subsequently, 104 cattle received a live vaccine of this strain by inoculation, which induced immunoprotection after heterologous challenged exposure with a different A. marginale isolate. In this study 14% of the immunized cattle required treatment as compared with the control nonimmunized cattle, in which 56% required treatment. The A. marginale vaccine strains used for the immunization studies had MSP1a variable regions that were different from those used for the challenge exposure.

  5. Response of layer and broiler strain chickens to parenteral administration of a live Salmonella Typhimurium vaccine.

    PubMed

    Groves, Peter J; Sharpe, Sue M; Cox, Julian M

    2015-07-01

    Responses to the parenteral administration of a live aroA deletion Salmonella serovar Typhimurium vaccine given to three brown egg layer strains and two broiler strains were studied. Twenty-five birds of each strain were reared together in floor pens to 6 weeks of age and then moved as individual strains to new floor pens and injected with 10(8) colony forming units (CFU) per bird of the vaccine bacteria intramuscularly or subcutaneously, 10(6) CFU per bird subcutaneously, or phosphate buffered saline (PBS) subcutaneously as a vaccination control. Three birds of one layer strain were injected intramuscularly with 0.5mg/ bird S. Typhimurium lipopolysaccharide (LPS) to evaluate whether response was similar for vaccine and endotoxin. Birds were weighed, and rectal temperatures recorded at the time of injection, then observed over 24 hours. Rectal temperatures were measured and blood samples collected for serum IL-6 assay at 3 hours post injection (PI). At 12 hours PI blood samples were drawn for analyses for plasma phosphorus (P), glucose (Glu), cholesterol (Cho), aspartate transaminase (AST), total protein (Ptn) and creatinine kinase (CK). Blood was sampled 14 days PI and tested for serum antibody to S. Typhimurium. Vaccination resulted in significant seroconversion by 14 days PI in all strains compared to the controls. The three layer strains exhibited a clinical malaise, evident within 90 minutes of injection, lasting for 12 hours, with complete recovery by 24 hours PI. Only the 10(8) CFU dose given subcutaneously produced an increase in rectal temperature 3 hours PI. Vaccination had no effect on IL-6 or Ptn. All vaccine doses increased P and the higher dose by either route decreased Cho in all bird strains. The 10(8) vaccine dose increased Glu and intramuscular injection markedly elevated CK only in the layer strains. The response was not completely congruous with that to LPS alone. The results highlight the need for consideration of differences in response of

  6. Duplex PCR for differentiation of the vaccine strain Brucella suis S2 and B. suis biovar 1 from other strains of Brucella spp.

    PubMed

    Nan, Wenlong; Tan, Pengfei; Wang, Yong; Xu, Zouliang; Mao, Kairong; Peng, Daxin; Chen, Yiping

    2014-09-01

    Immunisation with attenuated Brucella spp. vaccines prevents brucellosis, but may also interfere with diagnosis. In this study, a duplex PCR was developed to distinguish Brucella suis vaccine strain S2 from field strains of B. suis biovar 1 and other Brucella spp. The PCR detected 60 fg genomic DNA of B. suis S2 or biovar 1 field strains and was able to distinguish B. suis S2 and wild-type strains of B. suis biovar 1 among 76 field isolates representing all the common species and biovars, as well as four vaccine strains, of Brucella.

  7. Safety of classical swine fever virus vaccine strain LOM in pregnant sows and their offspring.

    PubMed

    Lim, Seong-In; Song, Jae-Young; Kim, Jaejo; Hyun, Bang-Hun; Kim, Ha-Young; Cho, In-Soo; Kim, Byounghan; Woo, Gye-Hyeong; Lee, Jung-Bok; An, Dong-Jun

    2016-04-12

    The present study aimed to evaluate the safety of the classical swine fever virus (CSFV) vaccine strain LOM in pregnant sows. Pregnant sows with free CSFV antibody were inoculated with a commercial LOM vaccine during early pregnancy (day 38; n=3) or mid-pregnancy (days 49-59; n=11). In pregnant sows vaccinated during the early stages of gestation, abortion (day 109) was observed in one case, with two stillbirths and seven mummified fetuses. The viability of live-born piglets was 34.9% in sows vaccinated during mid-pregnancy compared with 81.8% in the control group. Post-mortem examination of the organs of the sows and piglets did not reveal any pathological lesions caused by CSFV; however, CSFV RNA was detected in the organs of several vaccinated sows and their litters. The LOM strain was transmitted from sows with free CSFV antibody to their fetus, but did not appear to induce immune tolerance in the offspring from vaccinated pregnant sows. Side effects were not observed in pregnant sows with antibody to the LOM strain: transmission from sow to their litters and stillbirth or mummified fetuses. The LOM strain may induce sterile immunity and provide rapid, long-lasting, and complete protection against CSFV; however, it should be contraindicated in pregnant sows due to potential adverse effects in pregnant sows with free CSFV antibody.

  8. Molecular relationship between field and vaccine strain of measles virus and its persistence in Pakistan

    PubMed Central

    2012-01-01

    Background Countrywide 5.9 million, 0-11 Month old children are immunized annually by EPI (Expended Program on Immunization) against 8 vaccine preventable diseases including measles and so on. Unfortunately the basic immunity centers are not uniform throughout the country. Each center provides services to about 27000 people which is inadequate. The purpose of this study was to explore the development of EPI Pakistan in terms of immunization of measles. Methods Nucleotide sequences were analyzed by neighbor joining method (bootstrap test) using Bio- edit and MEGA-5 software to find evolutionary relationship between wild type measles strain and vaccine strain (Edmonston strain) used in Pakistan. For statistical analysis of data SPSS 16 was used. Results Currently 1.3 vaccinators are working at each U C (union council) which according to national EPI policy should be at least 2. About 56% and 44% children of age 0-11 months did not received second dose of measles in the last two years respectively. Out of these 4231 cases which were reported last year, 1370 have received their first dose of measles vaccine. Conclusion Seroconversion and seroprevalence study of the vaccine and field strain of measles virus is needed to confirm whether its failure is due to service unavailability or vaccine in-affectivity. PMID:22284834

  9. Evaluation of European tick-borne encephalitis virus vaccine against recent Siberian and far-eastern subtype strains.

    PubMed

    Hayasaka, D; Goto, A; Yoshii, K; Mizutani, T; Kariwa, H; Takashima, I

    2001-09-14

    To evaluate the efficacy of the European TBE vaccine in east-Siberian and far-eastern regions of Russia, we examined the immune responses of the vaccine against recent TBE virus Siberian (Irkutsk) and far-eastern (Khabarovsk and Vladivostok) isolates. The sera of vaccinated humans showed efficient neutralizing antibody titers (> or =20) against Siberian and far-eastern strains. To evaluate the efficacy of the vaccine in vivo, mice were vaccinated and challenged with lethal doses of the viruses. All vaccinated mice survived each virus challenge. These results suggest that the European vaccine can prevent the TBE virus infection in east-Siberian and far-eastern regions of Russia.

  10. Modeling the impact of the 7-valent pneumococcal conjugate vaccine in Chinese infants: an economic analysis of a compulsory vaccination.

    PubMed

    Che, Datian; Zhou, Hua; He, Jinchun; Wu, Bin

    2014-02-07

    The purpose of this study was to compare, from a Chinese societal perspective, the projected health benefits, costs, and cost-effectiveness of adding pneumococcal conjugate heptavalent vaccine (PCV-7) to the routine compulsory child immunization schedule. A decision-tree model, with data and assumptions adapted for relevance to China, was developed to project the health outcomes of PCV-7 vaccination (compared with no vaccination) over a 5-year period as well as a lifetime. The vaccinated birth cohort included 16,000,000 children in China. A 2 + 1 dose schedule at US$136.51 per vaccine dose was used in the base-case analysis. One-way sensitivity analysis was used to test the robustness of the model. The impact of a net indirect effect (herd immunity) was evaluated. Outcomes are presented in terms of the saved disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. In a Chinese birth cohort, a PCV-7 vaccination program would reduce the number of pneumococcus-related infections by at least 32% and would prevent 2,682 deaths in the first 5 years of life, saving $1,190 million in total costs and gaining an additional 9,895 QALYs (discounted by 3%). The incremental cost per QALY was estimated to be $530,354. When herd immunity was taken into account, the cost per QALY was estimated to be $95,319. The robustness of the model was influenced mainly by the PCV-7 cost per dose, effectiveness herd immunity and incidence of pneumococcal diseases. With and without herd immunity, the break-even costs in China were $29.05 and $25.87, respectively. Compulsory routine infant vaccination with PCV-7 is projected to substantially reduce pneumococcal disease morbidity, mortality, and related costs in China. However, a universal vaccination program with PCV-7 is not cost-effective at the willingness-to-pay threshold that is currently recommended for China by the World Health Organization.

  11. Genotypic diversity in Babesia bovis field isolates and vaccine strains from South Africa.

    PubMed

    Combrink, M P; Troskie, P C; Pienaar, R; Latif, A A; Mans, B J

    2014-01-31

    Genotypic diversity in Babesia bovis (cause of Asiatic redwater in cattle) vaccine strains and field isolates from South Africa were investigated using the Bv80 gene as well as microsatellites. The S11 vaccine strain possessed both A and B alleles of the Bv80 gene, as well as genotypic diversity within each allele type as defined by repeat variation resulting in different amplicon sizes. Rapid serial passage of vaccine strain from passage S10 to S24 resulted in loss of genotypic diversity that yielded a single allele A genotype with an amplicon size of 558 bp. This suggested that clonal selection occurred during rapid passaging. Extensive genotypic diversity exists in 44 field isolates characterized with both Bv80 A and B alleles, but can be readily distinguished from the S24 vaccine strain using either the Bv80 allele specific PCR assays or using multi-locus micro-satellite typing. This indicated that no recent documented clinical cases of Asiatic redwater were caused by the reversion to virulence of the current vaccine strain.

  12. Development of a highly immunogenic Newcastle disease virus chicken vaccine strain of duck origin.

    PubMed

    Kim, J Y; Kye, S J; Lee, H J; Gaikwad, S; Lee, H S; Jung, S C; Choi, K S

    2016-04-01

    Newcastle disease virus (NDV) strain NDRL0901 was developed as a live vaccine candidate for control of Newcastle disease. NDV isolate KR/duck/13/07 (DK1307) of duck origin was used as the selected vaccine strain. DK1307 was passaged 6 times in chickens. Then a single clone from the chicken-adapted virus (DK1307C) was finally selected, and the vaccine strain was named NDRL0901. DK1307C and the clone NDRL0901 viruses showed enhanced immunogenicity compared to the DK1307 virus. Principal component analysis based on fusion and hemagglutinin-neuraminidase genes revealed the codon usage pattern in the dataset is distinct separating duck viral sequences and avian sequences, and passage of the duck origin virus into the chicken host causes deviation in the codon usage pattern. The NDRL0901 virus was avirulent and did not acquire viral virulence even after 7 back passages in chickens. When day-old chicks were vaccinated with the NDRL0901 virus via spray, eye drops, and drinking water, the vaccinated birds showed no clinical signs and had significant protection efficacy (>80%) against very virulent NDV (Kr005 strain) infection regardless of the administration route employed. The results indicate that the NDRL0901 strain is safe in chickens and can offer protective immunity.

  13. Effect of vaccination of pigs against experimental infection with high and low virulence Mycoplasma hyopneumoniae strains.

    PubMed

    Villarreal, I; Maes, D; Vranckx, K; Calus, D; Pasmans, F; Haesebrouck, F

    2011-02-17

    This study investigated the infection pattern and lung lesion development in pigs caused by a low and highly virulent Mycoplasma hyopneumoniae strain at 4 and 8 weeks (w) post infection (PI). It also determined the efficacy of a commercial inactivated whole-cell vaccine against infection with each one of these M. hyopneumoniae strains. Ninety piglets free of M. hyopneumoniae were selected, and 40 of them were randomly vaccinated during their first week of life. At weaning, all piglets were allocated to 10 different groups and housed in pens with absolute filters. At 4 weeks of age, pigs were inoculated intratracheally with either a highly virulent M. hyopneumoniae strain, a low virulent strain or with sterile culture medium. Half of all animals were euthanized at 4 w PI, while the remaining half was euthanized at 8 w PI. Coughing was assessed daily, and lung lesions, immunofluorescence (IF), bacteriological analysis and nested PCR were assessed after necropsy. It was demonstrated that contrary to the highly virulent strain, the low virulent strain required more than 4 weeks PI (commonly accepted as the standard infection model) to reach maximum clinical symptoms. Vaccination significantly reduced clinical symptoms, macroscopic and microscopic lung lesions in pigs infected with the highly virulent strain. This effect was more pronounced at 4 than at 8 weeks PI. Protective efficacy was also observed in pigs infected with the low virulent strain, but the effect was less pronounced than on the highly virulent strain.

  14. Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection.

    PubMed

    Haolla, Filipe A; Claser, Carla; de Alencar, Bruna C G; Tzelepis, Fanny; de Vasconcelos, José Ronnie; de Oliveira, Gabriel; Silvério, Jaline C; Machado, Alexandre V; Lannes-Vieira, Joseli; Bruna-Romero, Oscar; Gazzinelli, Ricardo T; dos Santos, Ricardo Ribeiro; Soares, Milena B P; Rodrigues, Mauricio M

    2009-09-18

    Immunisation with Amastigote Surface Protein 2 (asp-2) and trans-sialidase (ts) genes induces protective immunity in highly susceptible A/Sn mice, against infection with parasites of the Y strain of Trypanosoma cruzi. Based on immunological and biological strain variations in T. cruzi parasites, our goal was to validate our vaccination results using different parasite strains. Due to the importance of the CD8(+) T cells in protective immunity, we initially determined which strains expressed the immunodominant H-2K(k)-restricted epitope TEWETGQI. We tested eight strains, four of which elicited immune responses to this epitope (Y, G, Colombian and Colombia). We selected the Colombian and Colombia strains for our studies. A/Sn mice were immunised with different regimens using both T. cruzi genes (asp-2 and ts) simultaneously and subsequently challenged with blood trypomastigotes. Immune responses before the challenge were confirmed by the presence of specific antibodies and peptide-specific T cells. Genetic vaccination did not confer protective immunity against acute infection with a lethal dose of the Colombian strain. In contrast, we observed a drastic reduction in parasitemia and a significant increase in survival, following challenge with an otherwise lethal dose of the Colombia strain. In many surviving animals with late-stage chronic infection, we observed alterations in the heart's electrical conductivity, compared to naive mice. In summary, we concluded that immunity against T. cruzi antigens, similar to viruses and bacteria, may be strain-specific and have a negative impact on vaccine development.

  15. Comparison of the Live Attenuated Yellow Fever Vaccine 17D-204 Strain to Its Virulent Parental Strain Asibi by Deep Sequencing

    PubMed Central

    Beck, Andrew; Tesh, Robert B.; Wood, Thomas G.; Widen, Steven G.; Ryman, Kate D.; Barrett, Alan D. T.

    2014-01-01

    Background. The first comparison of a live RNA viral vaccine strain to its wild-type parental strain by deep sequencing is presented using as a model the yellow fever virus (YFV) live vaccine strain 17D-204 and its wild-type parental strain, Asibi. Methods. The YFV 17D-204 vaccine genome was compared to that of the parental strain Asibi by massively parallel methods. Variability was compared on multiple scales of the viral genomes. A modeled exploration of small-frequency variants was performed to reconstruct plausible regions of mutational plasticity. Results. Overt quasispecies diversity is a feature of the parental strain, whereas the live vaccine strain lacks diversity according to multiple independent measurements. A lack of attenuating mutations in the Asibi population relative to that of 17D-204 was observed, demonstrating that the vaccine strain was derived by discrete mutation of Asibi and not by selection of genomes in the wild-type population. Conclusions. Relative quasispecies structure is a plausible correlate of attenuation for live viral vaccines. Analyses such as these of attenuated viruses improve our understanding of the molecular basis of vaccine attenuation and provide critical information on the stability of live vaccines and the risk of reversion to virulence. PMID:24141982

  16. Comparison of the live attenuated yellow fever vaccine 17D-204 strain to its virulent parental strain Asibi by deep sequencing.

    PubMed

    Beck, Andrew; Tesh, Robert B; Wood, Thomas G; Widen, Steven G; Ryman, Kate D; Barrett, Alan D T

    2014-02-01

    The first comparison of a live RNA viral vaccine strain to its wild-type parental strain by deep sequencing is presented using as a model the yellow fever virus (YFV) live vaccine strain 17D-204 and its wild-type parental strain, Asibi. The YFV 17D-204 vaccine genome was compared to that of the parental strain Asibi by massively parallel methods. Variability was compared on multiple scales of the viral genomes. A modeled exploration of small-frequency variants was performed to reconstruct plausible regions of mutational plasticity. Overt quasispecies diversity is a feature of the parental strain, whereas the live vaccine strain lacks diversity according to multiple independent measurements. A lack of attenuating mutations in the Asibi population relative to that of 17D-204 was observed, demonstrating that the vaccine strain was derived by discrete mutation of Asibi and not by selection of genomes in the wild-type population. Relative quasispecies structure is a plausible correlate of attenuation for live viral vaccines. Analyses such as these of attenuated viruses improve our understanding of the molecular basis of vaccine attenuation and provide critical information on the stability of live vaccines and the risk of reversion to virulence.

  17. Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium.

    PubMed

    Zeller, Mark; Heylen, Elisabeth; Tamim, Sana; McAllen, John K; Kirkness, Ewen F; Akopov, Asmik; De Coster, Sarah; Van Ranst, Marc; Matthijnssens, Jelle

    2017-01-01

    G1P[8] rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P[8] rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P[8] rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction) to investigate the impact of rotavirus vaccine introduction on circulating G1P[8] strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P[8] strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P[8] strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P[8] strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out.

  18. Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium

    PubMed Central

    Heylen, Elisabeth; Tamim, Sana; McAllen, John K.; Kirkness, Ewen F.; Akopov, Asmik; De Coster, Sarah; Van Ranst, Marc; Matthijnssens, Jelle

    2017-01-01

    G1P[8] rotaviruses are responsible for the majority of human rotavirus infections worldwide. The effect of universal mass vaccination with rotavirus vaccines on circulating G1P[8] rotaviruses is still poorly understood. Therefore we analyzed the complete genomes of the Rotarix™ vaccine strain, and 70 G1P[8] rotaviruses, detected between 1999 and 2010 in Belgium (36 before and 34 after vaccine introduction) to investigate the impact of rotavirus vaccine introduction on circulating G1P[8] strains. All rotaviruses possessed a complete Wa-like genotype constellation, but frequent intra-genogroup reassortments were observed as well as multiple different cluster constellations circulating in a single season. In addition, identical cluster constellations were found to circulate persistently over multiple seasons. The Rotarix™ vaccine strain possessed a unique cluster constellation that was not present in currently circulating G1P[8] strains. At the nucleotide level, the VP6, VP2 and NSP2 gene segments of Rotarix™ were relatively distantly related to any Belgian G1P[8] strain, but other gene segments of Rotarix™ were found in clusters also containing circulating Belgian strains. At the amino acid level, the genetic distance between Rotarix™ and circulating Belgian strains was considerably lower, except for NSP1. When we compared the Belgian G1P[8] strains collected before and after vaccine introduction a reduction in the proportion of strains that were found in the same cluster as the Rotarix™ vaccine strain was observed for most gene segments. The reduction in the proportion of strains belonging to the same cluster may be the result of the vaccine introduction, although natural fluctuations cannot be ruled out. PMID:28070453

  19. Brucella abortus strain RB51 vaccination in elk. I. Efficacy of reduced dosage.

    PubMed

    Cook, Walter E; Williams, Elizabeth S; Thorne, E Tom; Kreeger, Terry J; Stout, Glen; Bardsley, Katie; Edwards, Hank; Schurig, Gerhardt; Colby, Lesley A; Enright, Fred; Elzer, Philip H

    2002-01-01

    Bovine brucellosis is a serious zoonotic disease affecting some populations of Rocky Mountain elk (Cervus elaphus nelsoni) and bison (Bison bison) in the Greater Yellowstone Area, USA. The fear that elk and/or bison may spread Brucella abortus to livestock has prompted efforts to reduce or eliminate the disease in wildlife. Brucella abortus strain RB51 (RB51) vaccine has recently been approved for use in cattle. Unlike strain 19 vaccine, RB51 does not cause false positive reactions on standard brucellosis serologic tests. If effective, it may become the vaccine of choice for wildlife. In February 1995, 45 serologically negative female elk calves were trapped and taken to the Sybille Wildlife Research and Conservation Education Unit near Wheatland, Wyoming, USA. In May 1995, 16 of these elk calves were hand-vaccinated with 1 x 10(9) colony forming units (CFU) of RB51, 16 were vaccinated with 1 x 10(8) CFU RB51 by biobullet, and 13 were given a saline placebo. The elk were bred in fall of 1996 and they were challenged with 1 x 10(7) CFU of B. abortus strain 2308 by intraconjunctival inoculation in March 1997. Thirteen (100%) control elk aborted, 14 (88%) hand-vaccinated elk aborted, and 12 (75%) biobullet vaccinated elk aborted or produced nonviable calves. These results suggest that a single dose of 1 x 10(8) to 1 x 10(9) CFU RB51 does not provide significant protection against B. abortus induced abortion in elk. However, the vaccine appears to be safe at this dose and additional study may reveal a more effective RB51 vaccine regimen for elk.

  20. Whole-Genome Sequence of a Bordetella pertussis Brazilian Vaccine Strain.

    PubMed

    Akamatsu, M A; Nishiyama, M Y; Morone, M; Oliveira, U C; Bezerra, M F B; Sakauchi, M A; Raw, I; Junqueira de Azevedo, I L M; Kitajima, J P; Carvalho, E; Ho, P L

    2015-02-19

    Despite the reduction in incidence after vaccination, pertussis disease is still considered a public health problem worldwide, mainly due to recent and potential new outbreaks. We report here the complete genome of the Bordetella pertussis Butantan strain used in the Brazilian National Immunization Program as a whole-cell pertussis antigen to compose vaccines such as DTwP (diphtheria, tetanus, and whole-cell pertussis). Copyright © 2015 Akamatsu et al.

  1. Whole-Genome Sequence of a Bordetella pertussis Brazilian Vaccine Strain

    PubMed Central

    Akamatsu, M. A.; Nishiyama, M. Y.; Morone, M.; Oliveira, U. C.; Bezerra, M. F. B.; Sakauchi, M. A.; Raw, I.; Junqueira de Azevedo, I. L. M.; Kitajima, J. P.; Ho, P. L.

    2015-01-01

    Despite the reduction in incidence after vaccination, pertussis disease is still considered a public health problem worldwide, mainly due to recent and potential new outbreaks. We report here the complete genome of the Bordetella pertussis Butantan strain used in the Brazilian National Immunization Program as a whole-cell pertussis antigen to compose vaccines such as DTwP (diphtheria, tetanus, and whole-cell pertussis). PMID:25700409

  2. Immune Responses and Safety after Dart or Booster Vaccination of Bison with Brucella abortus Strain RB51

    PubMed Central

    Johnson, C.

    2012-01-01

    One alternative for management of brucellosis in Yellowstone National Park bison (Bison bison) is vaccination of calves and yearlings. Although Brucella abortus strain RB51 vaccination protects bison against experimental challenge, the effect of booster vaccinations was unknown. This study characterized immunologic responses after dart or booster vaccination of bison with Brucella abortus strain RB51. In two studies, 8- to 10-month-old female bison were inoculated with saline (n = 14), hand vaccinated with 1.1 × 1010 to 2.0 × 1010 CFU of RB51 (n = 21), or dart vaccinated with 1.8 × 1010 CFU of RB51 (n = 7). A subgroup of hand vaccinates in study 1 was randomly selected for booster vaccination 15 months later with 2.2 × 1010 CFU of RB51. Compared to single vaccinates, booster-vaccinated bison had greater serologic responses to RB51. However, there was a trend for antigen-specific proliferative responses of peripheral blood mononuclear cells (PBMC) from booster vaccinates to be reduced compared to responses of PBMC from single vaccinates. PBMC from booster vaccinates tended to have greater gamma interferon (IFN-γ) production than those from single vaccinates. In general, dart vaccination with RB51 induced immunologic responses similar to those of hand vaccination. All vaccinates (single hand, dart, or booster) demonstrated greater (P < 0.05) immunologic responses at various times after vaccination than nonvaccinated bison. Booster vaccination with RB51 in early gestation did not induce abortion or fetal infection. Our data suggest that booster vaccination does not induce strong anamnestic responses. However, phenotypic data on resistance to experimental challenge are required to fully assess the effect of booster vaccination on protective immunity. PMID:22461528

  3. Immune responses and safety after dart or booster vaccination of bison with Brucella abortus strain RB51.

    PubMed

    Olsen, S C; Johnson, C

    2012-05-01

    One alternative for management of brucellosis in Yellowstone National Park bison (Bison bison) is vaccination of calves and yearlings. Although Brucella abortus strain RB51 vaccination protects bison against experimental challenge, the effect of booster vaccinations was unknown. This study characterized immunologic responses after dart or booster vaccination of bison with Brucella abortus strain RB51. In two studies, 8- to 10-month-old female bison were inoculated with saline (n = 14), hand vaccinated with 1.1 × 10(10) to 2.0 × 10(10) CFU of RB51 (n = 21), or dart vaccinated with 1.8 × 10(10) CFU of RB51 (n = 7). A subgroup of hand vaccinates in study 1 was randomly selected for booster vaccination 15 months later with 2.2 × 10(10) CFU of RB51. Compared to single vaccinates, booster-vaccinated bison had greater serologic responses to RB51. However, there was a trend for antigen-specific proliferative responses of peripheral blood mononuclear cells (PBMC) from booster vaccinates to be reduced compared to responses of PBMC from single vaccinates. PBMC from booster vaccinates tended to have greater gamma interferon (IFN-γ) production than those from single vaccinates. In general, dart vaccination with RB51 induced immunologic responses similar to those of hand vaccination. All vaccinates (single hand, dart, or booster) demonstrated greater (P < 0.05) immunologic responses at various times after vaccination than nonvaccinated bison. Booster vaccination with RB51 in early gestation did not induce abortion or fetal infection. Our data suggest that booster vaccination does not induce strong anamnestic responses. However, phenotypic data on resistance to experimental challenge are required to fully assess the effect of booster vaccination on protective immunity.

  4. Differentiation of Erysipelothrix rhusiopathiae strains by nucleotide sequence analysis of a hypervariable region in the spaA gene: discrimination of a live vaccine strain from field isolates.

    PubMed

    Nagai, Shinya; To, Ho; Kanda, Akira

    2008-05-01

    Erysipelothrix rhusiopathiae causes erysipelas in swine and is considered a reemerging disease contributing substantially to economic losses in the swine industry. Since an attenuated live vaccine was commercialized in 1974 in Japan, outbreaks of acute septicemia or subacute urticaria of erysipelas have decreased dramatically. In contrast, a chronic form of erysipelas found during meat inspections in slaughterhouses has been increasing. In this study, a new strain-typing method was developed based on nucleotide sequencing of a hypervariable region in the surface protective antigen (spaA) gene for discrimination of the live vaccine strain from field isolates. Sixteen strains isolated from arthritic lesions found in slaughtered pigs were segregated into 4 major patterns: 1) identical nucleotide sequence with the vaccine strain: 3 isolates; 2) 1 nucleotide substitution (C to A) at position 555: 5 isolates; 3) 1 nucleotide substitution at various positions: 5 isolates; and 4) 2 nucleotide substitutions: 3 isolates. Isolates with the same nucleotide sequence as the vaccine strain were further characterized by other properties, including the mouse pathogenicity test. One strain isolated from pigs on a farm where the live vaccine had been used was found to be closely related to the vaccine strain. The phylogenetic tree constructed based on the spaA sequence suggests that the evolutionary distance of the isolates is related to the pathogenicity in mice. The new strain-typing system based on nucleotide sequencing of the spaA region is useful to discriminate the vaccine strain from field isolates.

  5. Strain Selection for Generation of O-Antigen-Based Glycoconjugate Vaccines against Invasive Nontyphoidal Salmonella Disease

    PubMed Central

    Saul, Allan; MacLennan, Calman A.; Micoli, Francesca; Rondini, Simona

    2015-01-01

    Nontyphoidal Salmonellae, principally S. Typhimurium and S. Enteritidis, are a major cause of invasive bloodstream infections in sub-Saharan Africa with no vaccine currently available. Conjugation of lipopolysaccharide O-antigen to a carrier protein constitutes a promising vaccination strategy. Here we describe a rational process to select the most appropriate isolates of Salmonella as source of O-antigen for developing a bivalent glycoconjugate vaccine. We screened a library of 30 S. Typhimurium and 21 S. Enteritidis in order to identify the most suitable strains for large scale O-antigen production and generation of conjugate vaccines. Initial screening was based on growth characteristics, safety profile of the isolates, O-antigen production, and O-antigen characteristics in terms of molecular size, O-acetylation and glucosylation level and position, as determined by phenol sulfuric assay, NMR, HPLC-SEC and HPAEC-PAD. Three animal isolates for each serovar were identified and used to synthesize candidate glycoconjugate vaccines, using CRM197 as carrier protein. The immunogenicity of these conjugates and the functional activity of the induced antibodies was investigated by ELISA, serum bactericidal assay and flow cytometry. S. Typhimurium O-antigen showed high structural diversity, including O-acetylation of rhamnose in a Malawian invasive strain generating a specific immunodominant epitope. S. Typhimurium conjugates provoked an anti-O-antigen response primarily against the O:5 determinant. O-antigen from S. Enteritidis was structurally more homogeneous than from S. Typhimurium, and no idiosyncratic antibody responses were detected for the S. Enteritidis conjugates. Of the three initially selected isolates, two S. Typhimurium (1418 and 2189) and two S. Enteritidis (502 and 618) strains generated glycoconjugates able to induce high specific antibody levels with high breadth of serovar-specific strain coverage, and were selected for use in vaccine production. The

  6. Differentiation of wild-type varicella-zoster strains from India and the Oka vaccine strain using a VZV open reading frame - 62 based PCR-RFLP technique.

    PubMed

    Kaushik, Karishma S; Lahiri, Kunal K; Kapila, Ketoki; Kumar, Satish; Gupta, Rajiv M; Karade, Santosh

    2008-08-01

    Since the introduction of varicella vaccination in India, surveillance of circulating VZV strains has gained significance. Differentiating wild-type VZV strains from the Oka vaccine strain can be achieved only by molecular genotyping methods. The development of PCR methods for VZV strain differentiation has been hampered by the fact that the VZV genome is highly conserved. We used VZV ORF 62 PCR-RFLP analysis to identify and differentiate wild-type VZV strains in India from the Oka vaccine strain. Digestion of VZV ORF 62 amplicons with SmaI, enabled accurate strain differentiation; the Oka strain was positive for three SmaI sites, compared to two SmaI sites in the wild-type VZV strains that we tested.

  7. Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms

    PubMed Central

    Zhang, Lu; Ru, Huan-wei; Chen, Fu-zeng; Jin, Chun-yan; Sun, Rui-feng; Fan, Xiao-yong; Guo, Ming; Mai, Jun-tao; Xu, Wen-xi; Lin, Qing-xia; Liu, Jun

    2016-01-01

    Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development. PMID:26643797

  8. Vaccination with a modified-live bovine viral diarrhea virus (BVDV) type 1a vaccine completely protected calves against challenge with BVDV type 1b strains.

    PubMed

    Xue, Wenzhi; Mattick, Debra; Smith, Linda; Umbaugh, Jerry; Trigo, Emilio

    2010-12-10

    Vaccination plays a significant role in the control of bovine viral diarrhea virus (BVDV) infection and spread. Recent studies revealed that type 1b is the predominant BVDV type 1 subgenotype, representing more than 75% of field isolates of BVDV-1. However, nearly all current, commercially available BVDV type 1 vaccines contain BVDV-1a strains. Previous studies have indicated that anti-BVDV sera, induced by BVDV-1a viruses, show less neutralization activity to BVDV-1b isolates than type 1a. Therefore, it is critically important to evaluate BVDV-1a vaccines in their ability to prevent BVDV-1b infection in calves. In current studies, calves were vaccinated subcutaneously, intradermally or intranasally with a single dose of a multivalent, modified-live viral vaccine containing a BVDV-1a strain, and were challenged with differing BVDV-1b strains to determine the efficacy and duration of immunity of the vaccine against these heterologous virus strains. Vaccinated calves, in all administration routes, were protected from respiratory disease caused by the BVDV-1b viruses, as indicated by significantly fewer clinical signs, lower rectal temperatures, reduced viral shedding and greater white blood cell counts than non-vaccinated control animals. The BVDV-1a vaccine elicited efficacious protection in calves against each BVDV-1b challenge strain, with a duration of immunity of at least 6 months.

  9. FMD virus isolates: the candidate strains for polyvalent vaccine development in Ethiopia.

    PubMed

    Ayelet, G; Soressa, M; Sisay, T; Belay, A; Gelaye, E; Jembere, S; Skjerve, E; Asmare, K

    2013-06-01

    The study was conducted on foot-and-mouth disease (FMD) viruses with the aim of selecting appropriate vaccinal strain to control of FMD in Ethiopia. The study was conducted in two-dimensional virus neutralization assay to determine the antigenic relationship 'r' value between the candidate vaccine strains and field isolates. A total of 21 serotype O, 7 serotype A, and 8 serotype SAT 2 FMD viruses, which were isolated from cattle and swine. A couple of isolates from each serotype were identified as vaccine candidates in the trial (O-ETH/38/2005, O-ETH/58/2008, A-ETH/7/2008, A-ETH/6/2000, SAT2-ETH/76/2009 and SAT2-ETH/64/2009). The finding revealed all the vaccine candidate depicted high antigenic similarity, above the mean "r" value, to their own serotypes in the studied serotype population except for one serotype A field isolate, A-ETH/13/1981, with "r" value=0.14 and 0.25) which is significantly lower than the minimum requirement. In general, the result indicated that these candidate vaccinal strains can be used for polyvalent vaccine production in the country. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. A diagnostic protocol to identify water buffaloes (Bubalus bubalis) vaccinated with Brucella abortus strain RB51 vaccine.

    PubMed

    Tittarelli, Manuela; Atzeni, Marcello; Calistri, Paolo; Di Giannatale, Elisabetta; Ferri, Nicola; Marchi, Enrico; Martucciello, Alessandra; De Massis, Fabrizio

    2015-01-01

    The use of live vaccine strain RB51 for vaccination of domestic water buffaloes (Bubalus bubalis) at risk of infection with Brucella abortus is permitted notwithstanding the plans for the eradication and only under strict veterinary control. The antibodies induced by RB51 vaccination are not detectable using conventional diagnostic techniques; therefore, it is necessary to have a specific diagnostic tool able to discriminate vaccinated from unvaccinated animals. The combination of a complement fixation test (CFT) with specific RB51 antigen (RB51-CFT) and a brucellin skin test has been demonstrated to be a reliable diagnostic system to identify single cattle (Bos taurus) vaccinated with RB51. So far, no data are available in the international scientific literature regarding the use of this test association in water buffalo. For this reason the suitability of this test combination has been evaluated in a water buffalo herd. One hundred twenty-seven animals farmed in a herd of Salerno province (Campania, Southern Italy), in the context of a presumptive unauthorized use of RB51 vaccine were chosen for this study. All tested animals resulted negative to Rose Bengal test (RBT) and complement fixation test (CFT) used for the detection of specific antibodies against Brucella field strains. Seventy-one animals (56%) developed RB51 antigen-specific CFT (RB51-CFT) antibodies against RB51 vaccine in a first sampling, while 104 animals (82%) gave positive result to a second serum sampling conducted 11 days after the intradermal inoculation of the RB51 brucellin. One hundred and seven animals (84%) showed a positive reaction to the RB51-CFT in at least 1 sampling, while 111 animals (87%) resulted positive to the RB51 brucellin skin test. Thus, analysing the results of the 3 testing in parallel, 119 animals (94%) were positive to at least 1 of the performed tests. The results suggest that the use in parallel of the RB51 brucellin skin test with RB51-CFT may represent a reliable

  11. [Production of a vaccine against enterotoxemia from Clostridium perfringens strains isolated in the field].

    PubMed

    Cherfaoui, S; Kadra, B

    1992-01-01

    We have isolated eight strains of C. perfringens from cases of enterotoxaemia. Five of these strains have revealed themselves toxic with respective types (type "A":2, type "C":2, type "D":1). In order to produce anti-enterotoxaemia vaccine, we have proceeded at the cultivation in fermenter of isolated strains and reference strains CWA 35, CWC and CWD AF. At the end of fermentation, we have evaluated the two following parameters: obtained biomass, and toxin titers. With the two classes of strains we reached an important biomass but toxins titers relatively weak comparatively to that which is usually required. It will be necessary then, to demonstrate the immunogen value of the produced vaccines by testing their efficacity.

  12. Live Oral Cholera Vaccine: Evaluation of the Clinical Effectiveness of Two Strains in Humans

    PubMed Central

    Cash, Richard A.; Music, Stanley I.; Libonati, Joseph P.; Schwartz, Andrew R.; Hornick, Richard B.

    1974-01-01

    El Tor Ogawa C14-S5 and EW-6, two live vaccine candidate strains, were given to volunteers in varying doses with and without bicarbonate. Vibrios were found in the stool of one of 32 men given the vaccine strain, and only three men developed a significant titer rise (fourfold or greater) at 2 weeks of vibriocidal or antitoxic antibody. Five men who had previously received 109 organisms of the C14-S5 strain were challenged subsequently with virulent Ogawa 395 Vibrio cholerae. The rate of clinical infection in these men was no different than in unvaccinated controls. It was demonstrated that the live oral cholera vaccines did not remain viable in the intestine long enough to act antigenically. PMID:4426706

  13. Live oral cholera vaccine: evaluation of the clinical effectiveness of two strains in humans.

    PubMed

    Cash, R A; Music, S I; Libonati, J P; Schwartz, A R; Hornick, R B

    1974-10-01

    El Tor Ogawa C14-S5 and EW-6, two live vaccine candidate strains, were given to volunteers in varying doses with and without bicarbonate. Vibrios were found in the stool of one of 32 men given the vaccine strain, and only three men developed a significant titer rise (fourfold or greater) at 2 weeks of vibriocidal or antitoxic antibody. Five men who had previously received 10(9) organisms of the C14-S5 strain were challenged subsequently with virulent Ogawa 395 Vibrio cholerae. The rate of clinical infection in these men was no different than in unvaccinated controls. It was demonstrated that the live oral cholera vaccines did not remain viable in the intestine long enough to act antigenically.

  14. Oral vaccination with microencapsuled strain 19 vaccine confers enhanced protection against Brucella abortus strain 2308 challenge in red deer (Cervus elaphus elaphus).

    PubMed

    Arenas-Gamboa, Angela M; Ficht, Thomas A; Davis, Donald S; Elzer, Philip H; Kahl-McDonagh, Melissa; Wong-Gonzalez, Alfredo; Rice-Ficht, Allison C

    2009-10-01

    Bison (Bison bison) and elk (Cervus elaphus nelsoni) in the Greater Yellowstone Area (GYA), USA, are infected with Brucella abortus, the causative agent of bovine brucellosis, and they serve as a wildlife reservoir for the disease. Bovine brucellosis recently has been transmitted from infected elk to cattle in Montana, Wyoming, and Idaho and has resulted in their loss of brucellosis-free status. An efficacious Brucella vaccine with a delivery system suitable for wildlife would be a valuable tool in a disease prevention and control program. We evaluated Strain 19 (S19) in a sustained release vehicle consisting of alginate microspheres containing live vaccine. In a challenge study using red deer (Cervus elaphus elaphus) as a model for elk, alginate, a naturally occurring polymer combined with a protein of Fasciola hepatica vitelline protein B was used to microencapsulate S19. Red deer were orally or subcutaneously immunized with 1.5 x 10(10) colony-forming units (CFUs) using microencapsulated S19. Humoral and cellular profiles were analyzed bimonthly throughout the study. The vaccinated red deer and nonvaccinated controls were challenged 1 yr postimmunization conjunctivally with 1 x 10(9) CFUs of B. abortus strain 2308. Red deer vaccinated with oral microencapsulated S19 had a statistically significant lower bacterial tissue load compared with controls. These data indicate for the first time that protection against Brucella-challenge can be achieved by combining a commonly used vaccine with a novel oral delivery system such as alginate-vitelline protein B microencapsulation. This system is a potential improvement for efficacious Brucella-vaccine delivery to wildlife in the GYA.

  15. Inactivation of SAM-methyltransferase is the mechanism of attenuation of a historic louse borne typhus vaccine strain.

    PubMed

    Liu, Yan; Wu, Bin; Weinstock, George; Walker, David H; Yu, Xue-Jie

    2014-01-01

    Louse borne typhus (also called epidemic typhus) was one of man's major scourges, and epidemics of the disease can be reignited when social, economic, or political systems are disrupted. The fear of a bioterrorist attack using the etiologic agent of typhus, Rickettsia prowazekii, was a reality. An attenuated typhus vaccine, R. prowazekii Madrid E strain, was observed to revert to virulence as demonstrated by isolation of the virulent revertant Evir strain from animals which were inoculated with Madrid E strain. The mechanism of the mutation in R. prowazekii that affects the virulence of the vaccine was not known. We sequenced the genome of the virulent revertant Evir strain and compared its genome sequence with the genome sequences of its parental strain, Madrid E. We found that only a single nucleotide in the entire genome was different between the vaccine strain Madrid E and its virulent revertant strain Evir. The mutation is a single nucleotide insertion in the methyltransferase gene (also known as PR028) in the vaccine strain that inactivated the gene. We also confirmed that the vaccine strain E did not cause fever in guinea pigs and the virulent revertant strain Evir caused fever in guinea pigs. We concluded that a single nucleotide insertion in the methyltransferase gene of R. prowazekii attenuated the R. prowazekii vaccine strain E. This suggested that an irreversible insertion or deletion mutation in the methyl transferase gene of R. prowazekii is required for Madrid E to be considered a safe vaccine.

  16. Efficacy of dart or booster vaccination with strain RB51 in protecting bison against experimental Brucella abortus challenge

    USDA-ARS?s Scientific Manuscript database

    Vaccination is an effective tool for reducing the prevalence of brucellosis in natural hosts. In this study, we characterized the efficacy of the Brucella abortus strain RB51 (RB51) vaccine in bison when delivered by single intramuscular vaccination (Hand RB51), single pneumatic dart delivery (Dart ...

  17. Hepatitis C genotype 1 mosaic vaccines are immunogenic in mice and induce stronger T-cell responses than natural strains.

    PubMed

    Yusim, Karina; Dilan, Rebecca; Borducchi, Erica; Stanley, Kelly; Giorgi, Elena; Fischer, William; Theiler, James; Marcotrigiano, Joseph; Korber, Bette; Barouch, Dan H

    2013-02-01

    Despite improved hepatitis C virus (HCV) treatments, vaccines remain an effective and economic option for curtailing the epidemic. Mosaic protein HCV genotype 1 vaccine candidates designed to address HCV diversity were immunogenic in mice. They elicited stronger T-cell responses to NS3-NS4a and E1-E2 proteins than did natural strains, as assessed with vaccine-matched peptides.

  18. Evaluation of a thermostable Newcastle disease virus strain TS09-C as an in-ovo vaccine for chickens

    USDA-ARS?s Scientific Manuscript database

    In-ovo vaccination is an attractive immunization approach for poultry industry. However, most of the Newcastle disease virus (NDV) vaccine strains used after hatch are unsafe, as in-ovo vaccines, due to their high pathogenicity for chicken embryos. In this study, we evaluated the safety and immunoge...

  19. A pandemic influenza vaccine in India: from strain to sale within 12 months.

    PubMed

    Dhere, Rajeev; Yeolekar, Leena; Kulkarni, Prasad; Menon, Ravi; Vaidya, Vivek; Ganguly, Milan; Tyagi, Parikshit; Barde, Prajakt; Jadhav, Suresh

    2011-07-01

    In the event of a highly pathogenic influenza pandemic, the Indian subcontinent would need 1.2 billion doses of vaccine to immunize its entire population, double if two doses were required to assure immunity. Serum Institute of India Limited (SII) thus became one of six initial grantees of the World Health Organization (WHO) technology transfer initiative to create capacity in developing countries to manufacture H5N1 pandemic influenza vaccine. At the outbreak of the A(H1N1) 2009 influenza pandemic, experience gained from the H5N1 project was used to develop a live attenuated influenza vaccine (LAIV), since this was the only option for the level of surge capacity required for a large-scale immunization campaign in India. SII took <12 months to develop and market its LAIV intranasal vaccine from receipt of the seed strain from WHO. As of November 2010, over 2.5 million persons have been vaccinated with Nasovac(®) with no serious adverse reactions or vaccine failure after 3 months' post-marketing surveillance. The product has been submitted for prequalification by WHO for purchase by United Nations agencies. In parallel, SII also developed an inactivated influenza vaccine, and is currently looking to ensure the sustainability of its influenza vaccine manufacturing capacity.

  20. Brucella suis strain 2 vaccine is safe and protective against heterologous Brucella spp. infections.

    PubMed

    Zhu, Liangquan; Feng, Yu; Zhang, Ge; Jiang, Hui; Zhang, Zhen; Wang, Nan; Ding, Jiabo; Suo, Xun

    2016-01-12

    Brucellosis is a wide spread zoonotic disease that causes abortion and infertility in mammals and leads to debilitating, febrile illness in humans. Brucella abortus, Brucella melitensis and Brucella suis are the major pathogenic species to humans. Vaccination with live attenuated B. suis strain 2 (S2) vaccine is an essential and critical component in the control of brucellosis in China. The S2 vaccine is very effective in preventing brucellosis in goats, sheep, cattle and swine. However, there are still debates outside of China whether the S2 vaccine is able to provide protection against heterologous virulent Brucella species. We investigated the residual virulence, immunogenicity and protective efficacy of the S2 vaccine in BALB/c mice by determining bacteria persistence in spleen, serum antibody response, cellular immune response and protection against a heterologous virulent challenge. The S2 vaccine was of low virulence as there were no bacteria recovered in spleen four weeks post vaccination. The vaccinated mice developed Brucella-specific IgG in 2-3 weeks, and a burst production of IFN-γ at one week as well as a two-fold increase in TNF-α production. The S2 vaccine protected mice from a virulent challenge by B. melitensis M28, B. abortus 2308 and B. suis S1330, and the S2 vaccinated mice did not develop any clinical signs or tissue damage. Our study demonstrated that the S2 vaccine is of low virulence, stimulates good humoral and cellular immunity and protects animals against infection by heterologous, virulent Brucella species.

  1. Bacterial survival, lymph node pathology, and serological responses of bison (Bison bison) vaccinated with Brucella abortus strain RB51 or strain 19.

    PubMed

    Olsen, S C; Cheville, N F; Kunkle, R A; Palmer, M V; Jensen, A E

    1997-01-01

    From August 1993 to June 1994, 3 month-old bison (Bison bison) were vaccinated with Brucella abortus strain RB51 (SRB51, n = 6), strain 19 (S19, n = 3), or with saline (n = 1) and serologic responses and persistence of vaccine strains within lymph nodes were monitored. Bison vaccinated with S19 had granulomatous lymphadenitis and greater peak numbers of B. abortus than those vaccinated with SRB51. Bison vaccinated with RB51 had similar histological lesions and B. abortus were still present in lymph nodes at 16 weeks. Although antibodies against RB51 were produced, standard tube agglutination test responses of RB51-vaccinates remained negative. The histological lesions of B. abortus infections in bison were similar to those observed in cattle, but bison did not clear SRB51 as rapidly as cattle.

  2. [Immunogenicity and safety of vaccine preparations based on circulating Bordetella pertussis strains].

    PubMed

    Zaĭtsev, E M; Mertsalova, N Iu; Britsina, M V; Ozeretskovskaia, M N; Bazhanova, I G; Shinkarev, A S; Poddubikov, A V

    2014-01-01

    Study specific activity and safety ofvaccine preparations based on circulating B. pertussis strains with currently predominating allele variants of pertussis toxin (ptxA1) and pertactin (prn2) genes. B. pertussis strains isolated from pertussis patients in Moscow in 2001-2010 were grown in dense and liquid media. The content of separate antigens in B. pertussis strains was determined by EIA. Immunogenicity and safety of the preparations was determined in F1(CBAxC57B16) line mice. All the studied circulating B. pertussis strains expressed pertussis toxin (PT), filamentous hemagglutinin (FHA) and agglutinogens corresponding to the serovar. Whole-cell and acellular pertussis vaccines were prepared based on the circulating strains, and a highly productive recently isolated toxigenic B.pertussis strain that could be used for production ofpertussis vaccines was selected as a result of studies ofimmunogenic, toxic and sensibilizing properties. Vaccine preparations based on a B. pertussis strain adapted to growth in liquid media with pertussis toxin and pertactin ptxAl1 - prn2 gene allele variation characteristic for contemporary population are specifically active and safe.

  3. Characterization of Brucella abortus mutant strain Δ22915, a potential vaccine candidate.

    PubMed

    Bao, Yanqing; Tian, Mingxing; Li, Peng; Liu, Jiameng; Ding, Chan; Yu, Shengqing

    2017-04-04

    Brucellosis, caused by Brucella spp., is an important zoonosis worldwide. Vaccination is an effective strategy for protection against Brucella infection in livestock in developing countries and in wildlife in developed countries. However, current vaccine strains including S19 and RB51 are pathogenic to humans and pregnant animals, limiting their use. In this study, we constructed the Brucella abortus (B. abortus) S2308 mutant strain Δ22915, in which the putative lytic transglycosylase gene BAB_RS22915 was deleted. The biological properties of mutant strain Δ22915 were characterized and protection of mice against virulent S2308 challenge was evaluated. The mutant strain Δ22915 showed reduced survival within RAW264.7 cells and survival in vivo in mice. In addition, the mutant strain Δ22915 failed to escape fusion with lysosomes within host cells, and caused no observable pathological damage. RNA-seq analysis indicated that four genes associated with amino acid/nucleotide transport and metabolism were significantly upregulated in mutant strain Δ22915. Furthermore, inoculation of ∆22915 at 10(5) colony forming units induced effective host immune responses and long-term protection of BALB/c mice. Therefore, mutant strain ∆22915 could be used as a novel vaccine candidate in the future to protect animals against B. abortus infection.

  4. Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies

    PubMed Central

    Payne, Ruth O.; Silk, Sarah E.; Elias, Sean C.; Milne, Kathryn H.; Rawlinson, Thomas A.; Llewellyn, David; Shakri, A. Rushdi; Jin, Jing; Labbé, Geneviève M.; Edwards, Nick J.; Poulton, Ian D.; Roberts, Rachel; Farid, Ryan; Jørgensen, Thomas; Alanine, Daniel G.W.; de Cassan, Simone C.; Higgins, Matthew K.; Otto, Thomas D.; McCarthy, James S.; de Jongh, Willem A.; Nicosia, Alfredo; Moyle, Sarah; Hill, Adrian V.S.; Berrie, Eleanor; Chitnis, Chetan E.; Lawrie, Alison M.; Draper, Simon J.

    2017-01-01

    BACKGROUND. Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite’s Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vaccination. METHODS. Safety and immunogenicity of replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and modified vaccinia virus Ankara (MVA) viral vectored vaccines targeting PvDBP_RII (Salvador I strain) were assessed in an open-label dose-escalation phase Ia study in 24 healthy UK adults. Vaccines were delivered by the intramuscular route in a ChAd63-MVA heterologous prime-boost regimen using an 8-week interval. RESULTS. Both vaccines were well tolerated and demonstrated a favorable safety profile in malaria-naive adults. PvDBP_RII–specific ex-vivo IFN-γ T cell, antibody-secreting cell, memory B cell, and serum IgG responses were observed after the MVA boost immunization. Vaccine-induced antibodies inhibited the binding of vaccine homologous and heterologous variants of recombinant PvDBP_RII to the DARC receptor, with median 50% binding-inhibition titers greater than 1:100. CONCLUSION. We have demonstrated for the first time to our knowledge that strain-transcending antibodies can be induced against the PvDBP_RII antigen by vaccination in humans. These vaccine candidates warrant further clinical evaluation of efficacy against the blood-stage P. vivax parasite. TRIAL REGISTRATION. Clinicaltrials.gov NCT01816113. FUNDING. Support was provided by the UK Medical Research Council, UK National Institute of Health Research Oxford Biomedical Research Centre, and the Wellcome Trust. PMID:28614791

  5. Genetic characterisation of the rabies virus vaccine strains used for oral immunization of foxes in Poland to estimate the effectiveness of vaccination.

    PubMed

    Orłowska, Anna; Żmudziński, Jan Franciszek

    2015-02-01

    The main reservoir of rabies virus in Poland has been the red fox. To control rabies in wildlife, oral immunization of foxes was introduced in 1993. The vaccine is effective when it confers immunity against the virus circulating in the environment. To assess the above issue, a study of the molecular characteristics of 570-bp fragments of the N and G genes of vaccine strains SAD B19 and SAD Bern against street virus strains was performed. The results confirmed the similarity of the vaccine strains and rabies virus strains circulating in the environment and also demonstrate the genetic stability of vaccine strains that have been distributed in Poland for 20 years.

  6. Case report: probable transmission of vaccine strain of yellow fever virus to an infant via breast milk.

    PubMed

    Kuhn, Susan; Twele-Montecinos, Loreto; MacDonald, Judy; Webster, Patricia; Law, Barbara

    2011-03-08

    The 17D yellow fever vaccine is a live-virus vaccine that has been in use since the 1940s. The incidence of encephalitis after yellow fever vaccination among young infants is much higher than among children older than nine months of age. Until recently, avoidance of vaccination by breastfeeding women who have received yellow fever vaccine had been based on theoretical grounds only. We report the probable transmission of vaccine strain of yellow fever virus from a mother to her infant through breastfeeding.

  7. Protective immune response of chickens to oral vaccination with thermostable live Fowlpox virus vaccine (strain TPV-1) coated on oiled rice.

    PubMed

    Wambura, Philemon N; Godfrey, S K

    2010-03-01

    The objective of the present study was to develop and evaluate a local vaccine (strain TPV-1) against Fowl pox (FP) in chickens. Two separate groups of chickens were vaccinated with FP vaccine through oral (coated on oiled rice) and wing web stab routes, respectively. The results showed that the haemagglutination-inhibition (HI) antibody titres in both vaccinated groups were comparable and significantly higher (P < 0.05) than the control chickens. It was further revealed that 14 days after vaccination HI GMT of > or =2 log(2) was recorded in chickens vaccinated by oral and wing web stab routes whereas 35 days after vaccination the HI antibody titres reached 5.6 log(2) and 6.3 log(2), respectively. Moreover, in both groups the birds showed 100% protection against challenge virus at 35 days after vaccination. The findings from the present study have shown that oral route is equally effective as wing web stab route for vaccination of chickens against FP. However, the oral route can be used in mass vaccination of birds thus avoid catching individual birds for vaccination. It was noteworthy that strain TPV-1 virus could be propagated by a simple allantoic cavity inoculation and harvesting of allantoic fluid where it survived exposure at 57 degrees C for 2 hours. If the oral vaccination technique is optimized it may be used in controlling FP in scavenging and feral chickens. In conclusion, the present study has shown that FP vaccine (strain TPV-1) was safe, thermostable, immunogenic and efficacious in vaccinated chickens.

  8. The haematological profile of female bronze turkeys (Meleagris gallopavo) vaccinated with various commercial strains of Newcastle disease.

    PubMed

    Schmidt, Elizabeth M d S; Santos, Ivan F C; Paulillo, António C; Martins, Gislaine R V; Denadai, Janine; Lapela, Ivan M

    2014-08-25

    The effects of vaccination on avian blood parameters are poorly understood. The present study was designed to evaluate whether different strains (Ulster 2C, B1, live LaSota and inactivated LaSota) of Newcastle disease vaccines had an effect on the haematological profile of female turkeys. Seventy-five female turkeys were allocated to treatment groups according to vaccination strain. All the birds, except those in the control group, were vaccinated at 32 weeks of age and revaccinated at 40 and 48 weeks of age. Blood samples were obtained for haematological analyses and serum samples for the haemagglutination inhibition test. Haemoglobin concentration was significantly lower (p < 0.05) in vaccinated female turkeys than in the control birds 28 days after vaccination. Monocytes were significantly higher (p < 0.05) in 44-week-old female turkeys vaccinated with inactivated LaSota strain compared with the other groups. Turkeys vaccinated with the B1 strain showed significantly higher (p < 0.05) total white blood cell counts compared with the other groups vaccinated with various commercial strains of the Newcastle disease virus. In conclusion, female turkeys showed significant differences in haemoglobin concentrations, monocytes and white blood cell counts when vaccinated against Newcastle disease.

  9. A Vero-cell-adapted vaccine donor strain of influenza A virus generated by serial passages.

    PubMed

    Hu, Weibin; Zhang, Hong; Han, Qinglin; Li, Li; Chen, Yixin; Xia, Ningshao; Chen, Ze; Shu, Yuelong; Xu, Ke; Sun, Bing

    2015-01-03

    A cell culture-based vaccine production system is preferred for the large-scale production of influenza vaccines and has advantages for generating vaccines against highly pathogenic influenza A viruses. Vero cells have been widely used in human vaccine manufacturing, and the safety of these cells has been well demonstrated. However, the most commonly used influenza-vaccine donor virus, A/Puerto Rico/8/1934 (PR8) virus, does not grow efficiently in Vero cells. Therefore, we adapted the PR8 virus to Vero cells by continuous passaging, and a high-growth strain was obtained after 20 passages. Sequence analysis and virological assays of the adapted strain revealed that mutations in four viral internal genes (NP, PB1, PA and NS1) were sufficient for adaptation. The recombinant virus harboring these mutations (PR8-4mut) displayed accelerated viral transport into the nucleus and increased RNP activity. Importantly, the PR8-4mut could serve as a backbone donor virus to support the growth of the H7N1, H9N2 and H5N1 avian viruses and the H1N1 and H3N2 human viruses in Vero cells without changing its pathogenicity in either chicken embryos or mice. Thus, our work describes the generation of a Vero-adapted, high-yield PR8-4mut virus that may serve as a promising candidate for an influenza-vaccine donor virus.

  10. Evaluation of the safety, immunogenicity and efficacy of three capripoxvirus vaccine strains against lumpy skin disease virus.

    PubMed

    Gari, Getachew; Abie, Getnet; Gizaw, Daniel; Wubete, Alehegn; Kidane, Membere; Asgedom, Hagos; Bayissa, Berecha; Ayelet, Gelagay; Oura, Christopher A L; Roger, Francois; Tuppurainen, Eeva S M

    2015-06-22

    The safety, immunogenicity and efficacy of three commercially available vaccines against lumpy skin disease (LSD) in cattle have been evaluated using a combination of vaccine challenge experiments and the monitoring of immune responses in vaccinated animals in the field. The three vaccines evaluated in the study included two locally produced (Ethiopian) vaccines (lumpy skin disease virus (LSDV) Neethling and Kenyan sheep and goat pox (KSGP) O-180 strain vaccines) and a Gorgan goat pox (GTP) vaccine manufactured by Jordan Bio-Industries Centre (JOVAC). The latter vaccine was evaluated for the first time in cattle against LSDV. The Ethiopian Neethling and KSGPO-180 vaccines failed to provide protection in cattle against LSDV, whereas the Gorgan GTP vaccine protected all the vaccinated calves from clinical signs of LSD. There was no significant difference in protective efficacy detected between two dosage levels (P=0.2, P=0.25, and P=0.1 for KSGP, Neethling and Gorgan vaccines, respectively). Additionally, the Gorgan GTP vaccinated cattle showed stronger levels of cellular immune responses measured using Delayed-Type Hypersensitivity (DTH) reactions at the vaccination site indicating higher levels of immunogenicity produced by the GTPV vaccine in cattle, as opposed to the other two vaccines. This study indicated, for the first time, that the Gorgan GTP vaccine can effectively protect cattle against LSDV and that the Neethling and KSGP O-180 vaccine were not protective. The results emphasise the need for molecular characterization of the Neethling and KSGP O-180 vaccine seed viruses used for vaccine production in Ethiopia. In addition, the potency and efficacy testing process of the Ethiopian LSD Neethling and KSGP O-180 vaccines should be re-evaluated.

  11. Cytokine responses in camels (Camelus bactrianus) vaccinated with Brucella abortus strain 19 vaccine.

    PubMed

    Odbileg, Raadan; Purevtseren, Byambaa; Gantsetseg, Dorj; Boldbaatar, Bazartseren; Buyannemekh, Tumurjav; Galmandakh, Zagd; Erdenebaatar, Janchivdorj; Konnai, Satoru; Onuma, Misao; Ohashi, Kazuhiko

    2008-02-01

    In the present study, we determined the levels of cytokines produced by camel (Camelus bactrianus) peripheral blood mononuclear cells (PBMCs) in response to live attenuated Brucella abortus (B. abortus) S19 vaccine. Seven camels were vaccinated with commercial B. abortus S19 vaccine, and their cytokine responses were determined using a real-time PCR assay. Cytokine responses to B. abortus S19 were examined at 6 hr, 48 hr and 1, 2 and 3 weeks post-vaccination. Serological tests were performed to further confirm these immune responses. The results revealed that IFN-gamma and IL-6 were upregulated during the first week post-vaccination. Low level expressions of IL-1alpha, IL-1beta, TNFalpha and IL-10 and no expression of IL-2 and IL-4 were observed compared with the control camels. The findings showed that B. abortus stimulates cell-mediated immunity by directly activating camel Th1 cells to secrete IFN-gamma. This quantification of cytokine expression in camels is essential for understanding of Camelidae disease development and protective immune responses. This is the first report of in vivo camel cytokine quantification after vaccination.

  12. Genetic Vaccination against Experimental Infection with Myotropic Parasite Strains of Trypanosoma cruzi

    PubMed Central

    Araújo, Adriano Fernando; de Oliveira, Gabriel; Vasconcelos, Juliana Fraga; Ersching, Jonatan; Dominguez, Mariana Ribeiro; Vasconcelos, José Ronnie; Machado, Alexandre Vieira; Gazzinelli, Ricardo Tostes; Bruna-Romero, Oscar; Soares, Milena Botelho; Rodrigues, Mauricio Martins

    2014-01-01

    In earlier studies, we reported that a heterologous prime-boost regimen using recombinant plasmid DNA followed by replication-defective adenovirus vector, both containing Trypanosoma cruzi genes encoding trans-sialidase (TS) and amastigote surface protein (ASP) 2, provided protective immunity against experimental infection with a reticulotropic strain of this human protozoan parasite. Herein, we tested the outcome of genetic vaccination of F1 (CB10XBALB/c) mice challenged with myotropic parasite strains (Brazil and Colombian). Initially, we determined that the coadministration during priming of a DNA plasmid containing the murine IL-12 gene improved the immune response and was essential for protective immunity elicited by the heterologous prime-boost regimen in susceptible male mice against acute lethal infections with these parasites. The prophylactic or therapeutic vaccination of resistant female mice led to a drastic reduction in the number of inflammatory infiltrates in cardiac and skeletal muscles during the chronic phase of infection with either strain. Analysis of the electrocardiographic parameters showed that prophylactic vaccination reduced the frequencies of sinus arrhythmia and atrioventricular block. Our results confirmed that prophylactic vaccination using the TS and ASP-2 genes benefits the host against acute and chronic pathologies caused by T. cruzi and should be further evaluated for the development of a veterinary or human vaccine against Chagas disease. PMID:25061263

  13. Construction of two Listeria ivanovii attenuated strains expressing Mycobacterium tuberculosis antigens for TB vaccine purposes.

    PubMed

    Lin, Qingqing; Zhou, Mengying; Xu, Zongkai; Khanniche, Asma; Shen, Hao; Wang, Chuan

    2015-02-20

    Bacillus Calmette-Guerin (BCG) has failed in complete control of tuberculosis (TB), thus, novel tuberculosis vaccines are urgently needed. We have constructed several TB vaccine candidates, which are characterized by the use of Listeria ivanovii (LI) strain as an antigen delivery vector. Two L. ivanovii attenuated recombinant strains L. ivanovii△actAplcB-Rv0129c and L. ivanovii△actAplcB-Rv3875 were successfully screened. Results from genome PCR and sequencing showed that the Mycobacterium tuberculosis antigen gene cassette coding for Ag85C or ESAT-6 protein respectively had been integrated into LI genome downstream of mpl gene. Western blot confirmed the secretion of Ag85C or ESAT-6 protein from the recombinant LI strains. These two recombinant strains showed similar growth curves as wide type strain in vitro. In vivo, they transiently propagated in mice spleen and liver, and induced specific CD8(+) IFN-γ secretion. Therefore, in this paper, two novel LI attenuated strains expressing specific TB antigens were successfully constructed. The promising growth characteristics in mice immune system and the capability of induction of IFN-γ secretion make them of potential interest for development of TB vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Attenuated strains of Mycobacterium avium subspecies paratuberculosis as vaccine candidates against Johne's disease.

    PubMed

    Settles, Erik W; Kink, John A; Talaat, Adel

    2014-04-11

    Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease in ruminants. Johne's disease has a severe economic impact on the dairy industry in the USA and worldwide. In an effort to combat this disease, we screened several transposon mutants that were attenuated in the murine model of paratuberculosis for the potential use as live attenuated vaccines. Using the murine model, two vaccine candidates (pgs1360, pgs3965 with mutations of fabG2_2 and umaA1, respectively) were at or below the limit of detection for tissue colonization suggesting their low level persistence and hence safety. Prior to challenge, both candidates induced a M. paratuberculosis-specific IFN-γ, an indication of eliciting cell-mediated immunity. Following challenge with a virulent strain of M. paratuberculosis, the two vaccine candidates significantly reduced bacterial colonization in organs with reduced histological scores compared to control animals. In addition, one of the vaccine candidates (pgs3965) also induced IL-17a, a cytokine associated with protective immunity in mycobacterial infection. Our analysis suggested that the pgs3965 vaccine candidate is a potential live-attenuated vaccine that could be tested further in ruminant models of paratuberculosis. The analysis also validated our screening strategy to identify effective vaccine candidates against intracellular pathogens.

  15. Choice of High-Efficacy Strains for the Annual Influenza Vaccine

    NASA Astrophysics Data System (ADS)

    Deem, Michael

    2005-03-01

    We introduce a model of protein evolution to explain limitations in the immune system response to vaccination and disease [1]. The phenomenon of original antigenic sin, wherein vaccination creates memory sequences that can increase susceptibility to future exposures to the same disease, is explained as stemming from localization of the immune system response in antibody sequence space. This localization is a result of the roughness in sequence space of the evolved antibody affinity constant for antigen and is observed for diseases with high year-to-year mutation rates, such as influenza. We show that the order parameter within this theory correlates well with efficacies of the H3N2 influenza A component of the annual vaccine between 1971 and 2004 [2,3]. This new measure of antigenic distance predicts vaccine efficacy significantly more accurately than do current state-of-the-art phylogenetic sequence analyses or ferret antisera inhibition assays. We discuss how this new measure of antigenic distance may be used in the context of annual influenza vaccine design and monitoring of vaccine efficacy. 1) M. W. Deem and H. Y. Lee, Phys. Rev. Lett. 91 (2003) 068101. 2) E. T. Munoz and M. W. Deem,q-bio.BM/0408016. 3) V. Gupta, D. J. Earl, and M. W. Deem, ``Choice of High-Efficacy Strains for the Annual Influenza Vaccine,'' submitted.

  16. Oral vaccination against bubonic plague using a live avirulent Yersinia pseudotuberculosis strain.

    PubMed

    Blisnick, Thierry; Ave, Patrick; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E

    2008-08-01

    We evaluated the possibility of using Yersinia pseudotuberculosis as a live vaccine against plague because it shares high genetic identity with Y. pestis while being much less virulent, genetically much more stable, and deliverable orally. A total of 41 Y. pseudotuberculosis strains were screened by PCR for the absence of the high pathogenicity island, the superantigens YPM, and the type IV pilus and the presence of the pYV virulence plasmid. One strain (IP32680) fulfilled these criteria. This strain was avirulent in mice upon intragastric or subcutaneous inoculation and persisted for 2 months in the mouse intestine without clinical signs of disease. IP32680 reached the mesenteric lymph nodes, spleen, and liver without causing major histological lesions and was cleared after 13 days. The antibodies produced in vaccinated animals recognized both Y. pseudotuberculosis and Y. pestis antigens efficiently. After a subcutaneous challenge with Y. pestis CO92, bacteria were found in low amounts in the organs and rarely in the blood of vaccinated animals. One oral IP32680 inoculation protected 75% of the mice, and two inoculations induced much higher antibody titers and protected 88% of the mice. Our results thus validate the concept that an attenuated Y. pseudotuberculosis strain can be an efficient, inexpensive, safe, and easy-to-produce live vaccine for oral immunization against bubonic plague.

  17. Draft Genome Sequence of the Vaccination Strain Mycobacterium bovis BCG S4-Jena

    PubMed Central

    Wibberg, Daniel; Winkler, Anika; Straube, Eberhard; Karrasch, Matthias; Keller, Peter M.

    2016-01-01

    Here, we present the draft genome sequence of Mycobacterium bovis BCG S4-Jena, a tuberculosis vaccine strain. The genome of S4-Jena is represented by 48 scaffolds, consisting of 132 scaffolded contigs and amounting to a size of about 4.2 Mb. New genes potentially encoding a phage fragment were identified in the genome. PMID:27103721

  18. Pathogenesis of a Chinese strain of bovine adenovirus type 3 infection in albino guinea pigs.

    PubMed

    Shi, Hong-Fei; Zhu, Yuan-Mao; Yan, Hao; Ma, Lei; Wang, Xue-Zhi; Xue, Fei

    2014-12-01

    Bovine adenovirus type 3 (BAV-3) is considered one of the most important respiratory tract agents of cattle and is widespread among cattle around the world. A BAV-3 strain was isolated from a bovine nasal swab for the first time in China in 2009 and named HLJ0955. Subsequently, BAV-3 has frequently been isolated from calves with respiratory diseases in China. To date, only limited study on the pathogenesis of BAV-3 infection in cotton rats has been conducted, and the pathogenesis of BAV-3 infection in guinea pigs has not been reported. Therefore, sixteen albino guinea pigs were inoculated intranasally with HLJ0955. All of the infected guinea pigs had apparently elevated rectal temperatures (39.2 °C-39.9 °C) at 2-7 days post-inoculation (PI). Consolidation and petechial hemorrhage were also observed in guinea pigs experimentally infected with HLJ0955. Viral replication was detectable by virus isolation and titration and by immunohistochemistry in the lungs of guinea pigs as early as 24 h PI. Viral DNA was detectable in the lungs of infected guinea pigs during 11 days of observation by real-time PCR. Virus-neutralizing antibodies against BAV-3 were detectable from 11 days PI and reached a peak titer at 15 days PI. Histopathological changes mainly occurred in the lungs of infected guinea pigs and were characterized by thickening of alveolar septa, mononuclear cell infiltration, hemorrhage and alveolar epithelial necrosis. These results indicate that HLJ0955 can replicate in the lungs of guinea pigs and cause fever and gross and histological lesions. The guinea pig infection model of BAV-3 would serve as a useful system for monitoring the infection process and pathogenesis of the Chinese BAV-3 strain HLJ0955, as well as immune responses to BAV-3 vaccines.

  19. Psychological Strains Found from In-depth Interviews with 105 Chinese Rural Young Suicides1

    PubMed Central

    Zhang, Jie; Dong, Nini; Delprino, Robert; Zhou, Li

    2009-01-01

    Perspective To investigate the role of different aspects of psychological strain in Chinese rural young suicides, so as to test the strain theory of suicide with the Chinese samples. Method Psychological Autopsy (PA) was conducted on 105 suicides in rural China. The background and deep reasons for suicide were obtained from in-depth interviews with survivors and close friends. For each suicide, a story is composed out of the provided information, and the stories were content-analyzed with the SPSS Text Analysis for Surveys™. Results Depression or other mental disorders were observed for less than half of the sampled suicides (42.9%). All suicides (100%) had experienced at least one type of the four strains: conflicting values, aspiration and reality, relative deprivation, and coping deficiency. While 24.9% of all suicides experienced only one type of strains, 36.2% for two strains, 32.4% for three, and only 6.7% of the suicides experienced all the four types of strains. Males are more likely than females to experience aspiration and deprivation strains, and the younger suicides (15-22 years of age) were more likely than the older suicides (23-29 years of age) to experience coping strain. Conclusion Psychological strains are more prevalent than mental disorders among Chinese rural young suicides. Mental illness might be a function of strain resulting from some negative life events, and future studies need to disentangle the relationship between strain and mental disorders. PMID:19363755

  20. Generation of a Genetically Stable High-Fidelity Influenza Vaccine Strain.

    PubMed

    Naito, Tadasuke; Mori, Kotaro; Ushirogawa, Hiroshi; Takizawa, Naoki; Nobusawa, Eri; Odagiri, Takato; Tashiro, Masato; Ohniwa, Ryosuke L; Nagata, Kyosuke; Saito, Mineki

    2017-03-15

    Vaccination is considered the most effective preventive means for influenza control. The development of a master virus with high growth and genetic stability, which may be used for the preparation of vaccine viruses by gene reassortment, is crucial for the enhancement of vaccine performance and efficiency of production. Here, we describe the generation of a high-fidelity and high-growth influenza vaccine master virus strain with a single V43I amino acid change in the PB1 polymerase of the high-growth A/Puerto Rico/8/1934 (PR8) master virus. The PB1-V43I mutation was introduced to increase replication fidelity in order to design an H1N1 vaccine strain with a low error rate. The PR8-PB1-V43I virus exhibited good replication compared with that of the parent PR8 virus. In order to compare the efficiency of egg adaptation and the occurrence of gene mutations leading to antigenic alterations, we constructed 6:2 genetic reassortant viruses between the A(H1N1)pdm09 and the PR8-PB1-V43I viruses; hemagglutinin (HA) and neuraminidase (NA) were from the A(H1N1)pdm09 virus, and the other genes were from the PR8 virus. Mutations responsible for egg adaptation mutations occurred in the HA of the PB1-V43I reassortant virus during serial egg passages; however, in contrast, antigenic mutations were introduced into the HA gene of the 6:2 reassortant virus possessing the wild-type PB1. This study shows that the mutant PR8 virus possessing the PB1 polymerase with the V43I substitution may be utilized as a master virus for the generation of high-growth vaccine viruses with high polymerase fidelity, low error rates of gene replication, and reduced antigenic diversity during virus propagation in eggs for vaccine production.IMPORTANCE Vaccination represents the most effective prophylactic option against influenza. The threat of emergence of influenza pandemics necessitates the ability to generate vaccine viruses rapidly. However, as the influenza virus exhibits a high mutation rate

  1. Screening vaccine candidate strains against Streptococcus agalactiae of tilapia based on PFGE genotype.

    PubMed

    Chen, Ming; Wang, Rui; Li, Li-Ping; Liang, Wan-Wen; Li, Jian; Huang, Yan; Lei, Ai-Ying; Huang, Wei-Yi; Gan, Xi

    2012-09-14

    The immunogenicity identification of epidemic strain is important for the development and application of vaccine. In this study, 85 Streptococcus agalactiae prevalent strains from the tilapia main cultured areas of China were distributed among 10 distinct PFGE genotypes (A-J). For each genotype, one representative strain (S.a(A)-S.a(J)) was selected to develop an inactivated whole-cell bacterial vaccine (V(A)-V(J)), which then underwent a protective immunity test. V(A)-V(J) showed similar relative percent survival (RPS) to the homologous or heterologous strains with the identical genotype, while the average RPS among V(A)-V(J) protecting against itself genotype strains showed large differences (44.71-98.81%). The RPS of V(A)-V(J) vaccinated fish against infections by the mixture of S.a(A)-S.a(J) at 15 days post vaccination (dpv) was ranged from 13.33% to 60.00%, and V(B), V(D), V(F), and V(G) showed the highest RPS of 60.00%, 46.67%, 53.33% and 60.00% respectively. V(B), V(D) and V(G) have their own specific protection scope, V(B) showed strong protective immunity to infections caused by A-D, F, G and J (53.57-100%), and V(G) showed strong protective immunity to C-H and J (50.00-100%), whereas V(D) showed weak protective immunity to all non-self genotype strains (14.81-36.67%). The results of the combined vaccination showed that V(G)+V(B) group had wider protection scope and higher RPS value than V(G)+V(D) group. Our results demonstrated that the protective immunity of S. agalactiae from tilapia was not only associated with their serotypes, but also related to their PFGE genotypes. It is difficult to acquire a single vaccine candidate strain that can protect against all genotype strains from the same serotype.

  2. Family Strain and Adolescent Delinquency in Two Chinese Cities, Guangzhou and Hong Kong

    ERIC Educational Resources Information Center

    Cheung, Chau-Kiu; Ngai, Ngan-Pun; Ngai, Steven Sek-Yum

    2007-01-01

    Elucidating the conditions in which family strain takes effect in adolescent delinquency is one avenue along which to substantiate general strain theory. These conditions include family relationship and the type of delinquency. In the context of Chinese societies, the conditions also include the differences between socialist, collectivist Mainland…

  3. Comparison of Antigenic Dominants of VP7 in G9 and G1 Rotavirus Strains Circulating in La Rioja, Argentina, with the Vaccine Strains.

    PubMed

    Cuffia, Valeria I; Díaz Ariza, María Del Carmen; Silvera, Alejandro; Sabini, Liliana I; Cordoba, Patricia A

    2016-01-01

    A massive vaccination in Argentina was implemented recently. The antigenic dominants of VP7 in G9 and G1 rotavirus strains, circulating in La Rioja, Argentina with strain vaccines were compared. From 2000 to 2010 in several attention centers of La Rioja, at northwestern Argentina, 418 stool samples from children younger than 5 years old were collected. Ninety were positive by immunochromatography and 51 were genotyped by reverse transcriptase-polymerase chain reaction followed by nested-multiplex polymerase chain reaction (PCR) with type-specific primers. Six G9 strains and four G1 strains were sequenced by MACROGEN Korea. The phylogenetic analysis was conducted in MEGA 6.0. The 940 bp were aligned using CLUSTALW and the tree was inferred using the UPGMA method. The antigenic dominants of VP7, 7-1a, 7-1b, and 7-2 were studied using BioEdit, 7.2.5. In the comparison between G9-lineage III d rotavirus (RV) strains circulating in La Rioja with ROTAVAC vaccine strain, three differences were detected corresponding to 100, 211, and 145 positions. In the comparison between G1-Lineage 1 strains and G1 Rotarix and G1 RotaTeq, three differences were observed in 94, 123, and 217 positions. All these positions were important for the escape to neutralization for study with monoclonal antibody. In conclusion, the differences between the G1 strains in La Rioja, Argentina and the G1 components of the RotaTeq and Rotarix vaccine strains are few, but important for the escape immunologic, and need to be monitored for appropriate evaluation of long-term impact of vaccine used in Argentina. Nevertheless, the VP7 antigenic regions of G9 RV strains circulating in La Rioja and ROTAVAC vaccine strains are different to other zones of Argentina and could play an important role in the failure of vaccine response in these regions and Argentina.

  4. Vaccination-challenge studies with a Port Chalmers/73 (H3N2)-based swine influenza virus vaccine: Reflections on vaccine strain updates and on the vaccine potency test.

    PubMed

    De Vleeschauwer, Annebel; Qiu, Yu; Van Reeth, Kristien

    2015-05-11

    The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu(®) and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0-7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998-2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test.

  5. Genetic and antigenic analyses of a Puumala virus isolate as a potential vaccine strain.

    PubMed

    Abu Daude, Nur Hardy; Kariwa, Hiroaki; Tkachenko, Evgeniy; Dzagurnova, Tamara; Medvedkina, Olga; Tkachenko, Petr; Ishizuka, Mariko; Seto, Takahiro; Miyashita, Daisuke; Sanada, Takahiro; Nakauchi, Mina; Yoshii, Kentaro; Maeda, Akihiko; Yoshimatsu, Kumiko; Arikawa, Jiro; Takashima, Ikuo

    2008-11-01

    Puumala virus (PUUV), a causative agent of hemorrhagic fever with renal syndrome (HFRS), is prevalent in Europe and European Russia. No vaccine has been developed for PUUV-associated HFRS, primarily because of the low viral yield in cultured cells. A PUUV strain known as DTK/Ufa-97 was isolated in Russia and adapted for growth in Vero E6 cells maintained in serum-free medium. The DTK/Ufa-97 strain produced a higher viral titer in serum-free medium, suggesting that it may prove useful in the development of an HFRS vaccine. When PUUV-infected Vero E6 cells were grown in serum-free medium, the DTK/Ufa-97 strain yielded more copies of intracellular viral RNA and a higher viral titer in the culture fluid than did the Sotkamo strain. Phylogenetic analysis revealed that PUUVs can be classified into multiple lineages according to geographical origin, and that the DTK/Ufa-97 strain is a member of the Bashkiria-Saratov lineage. The deduced amino acid sequences of the small, medium, and large segments of the DTK/Ufa-97 strain were 99.2% to 100%, 99.3% to 99.8%, and 99.8% identical, respectively, to those of the Bashkirian PUUV strains and 96.9%, 92.6%, and 97.4% identical, respectively, to those of the Sotkamo strain, indicating that the PUUVs are genetically diverse. However, DTK/Ufa-97 and other strains of PUUV exhibited similar patterns of binding to a panel of monoclonal antibodies against Hantaan virus. In addition, diluted antisera (i.e., ranging from 1:160 to 1:640) specific to three strains of PUUV neutralized both homologous and heterologous viruses. These results suggest that the DTK/Ufa-97 strain is capable of extensive growth and is antigenically similar to genetically distant strains of PUUV.

  6. Evaluation of a thermostable Newcastle disease virus strain TS09-C as an in-ovo vaccine for chickens

    PubMed Central

    Yu, Qingzhong; Wang, Hongling; Luo, Qingping; Zhang, Tengfei; Zhang, Rongrong; Zhang, Wanpo; Shao, Huabin

    2017-01-01

    In-ovo vaccination is an attractive immunization approach for poultry industry. However, most of the Newcastle disease virus (NDV) vaccine strains used after hatch are unsafe, as in-ovo vaccines, due to their high pathogenicity for chicken embryos. In this study, we evaluated the safety and immunogenicity of a thermostable NDV strain TS09-C, derived from V4 strain, as in-ovo vaccine. Chickens in-ovo vaccinated with the parental V4 strain displayed greatly reduced hatchability and severe histopathological lesions in both trachea and intestine tissues, while the hatchability was not affected by in-ovo vaccination withTS09-C strain. The safe dose that infected all chicken embryos without obviously histopathological lesions was 103.0 EID50 per bird. In-ovo vaccination of chickens with TS09-C virus conferred complete protection against virulent NDV challenge. Results suggest that the thermostable NDV strain TS09-C is a safe and immunogenic in-ovo vaccine candidate that can be delivered quickly and uniformly, and induce earlier immune response. PMID:28234989

  7. How direct competition shapes coexistence and vaccine effects in multi-strain pathogen systems.

    PubMed

    Gjini, Erida; Valente, Carina; Sá-Leão, Raquel; Gomes, M Gabriela M

    2016-01-07

    We describe an integrated modeling framework for understanding strain coexistence in polymorphic pathogen systems. Previous studies have debated the utility of neutral formulations and focused on cross-immunity between strains as a major stabilizing mechanism. Here we convey that direct competition for colonization mediates stable coexistence only when competitive abilities amongst pathogen clones satisfy certain pairwise asymmetries. We illustrate our ideas with nested SIS models of single and dual colonization, applied to polymorphic pneumococcal bacteria. By fitting the models to cross-sectional prevalence data from Portugal (before and after the introduction of a seven-valent pneumococcal conjugate vaccine), we are able to not only statistically compare neutral and non-neutral epidemiological formulations, but also estimate vaccine efficacy, transmission and competition parameters simultaneously. Our study highlights that the response of polymorphic pathogen populations to interventions holds crucial information about strain interactions, which can be extracted by suitable nested modeling.

  8. Vaccination with a BCG Strain Overexpressing Ag85B Protects Cattle against Mycobacterium bovis Challenge

    PubMed Central

    Rizzi, Caroline; Bianco, María Verónica; Blanco, Federico Carlos; Soria, Marcelo; Gravisaco, María José; Montenegro, Valeria; Vagnoni, Lucas; Buddle, Bryce; Garbaccio, Sergio; Delgado, Fernando; Leal, Karen Silva; Cataldi, Angel Adrián; Dellagostin, Odir Antônio; Bigi, Fabiana

    2012-01-01

    Mycobacterium bovis is the causative agent of tuberculosis in cattle but also infects other animals, including humans. Previous studies in cattle have demonstrated that the protection induced by BCG is not complete. In order to improve the protection efficacy of BCG, in this study we overexpressed Ag85B in a BCG Pasteur strain, by using an expression system based on the use of an auxotrophic strain for the leucine amino acid, and complementation with leuD. We found that vaccination of cattle with BCG overexpressing Ag85B induced higher production of IL-17 and IL-4 mRNA upon purified protein derivative (PPDB) stimulation of peripheral blood mononuclear cells (PBMCs) than vaccination with BCG. Moreover, the IL-17 mRNA expression after vaccination negatively correlated with disease severity resulting from a subsequent challenge with M. bovis, suggesting that this cytokine is a potential biomarker of cattle protection against bovine tuberculosis. Importantly, vaccination with the recombinant BCG vaccine protected cattle better than the wild-type BCG Pasteur. PMID:23251517

  9. Review of 10 years of marketing experience with Chinese domestic inactivated hepatitis A vaccine Healive®

    PubMed Central

    Wu, Jun-Yu; Liu, Yan; Chen, Jiang-Ting; Xia, Ming; Zhang, Xiao-Mei

    2012-01-01

    In 2002, the first Chinese domestic preservative-free inactivated hepatitis A vaccine, Healive®, was introduced in China. It is highly immunogenic, and provides lasting protection in healthy individuals and generates protective levels of antibodies in other at-risk individuals. Over 10 years since its first licensure, postmarketing surveillance data have confirmed the outstanding safety profile of the vaccine. Comparative clinical trials indicated that Healive® induce equal or similar immunogenicity with other currently available inactivated hepatitis A vaccines and are interchangeable for the course of HAV immunization in Chinese children. The vaccine is effective in curbing outbreaks of hepatitis A due to rapid seroconversion and the long incubation period of the disease. Additional issues surrounding the use of the vaccine are also reviewed. PMID:23032165

  10. Genetic characterization of vaccine and field strains of serotype A foot-and-mouth disease virus from India.

    PubMed

    Mohapatra, J K; Pawar, S S; Tosh, C; Subramaniam, S; Palsamy, R; Sanyal, A; Hemadri, D; Pattnaik, B

    2011-01-01

    Extreme antigenic and genetic heterogeneity of serotype A foot-and-mouth disease virus (FMDV) population has resulted in change of vaccine strains in India twice in the last decade. In such a situation, complete characterization of the vaccine strains is imperative. With regard to the frequent outbreaks of this disease, FMDV field strains are also of interest. Therefore three vaccine strains and two field strains of type A FMDV from India were completely sequenced and the obtained sequences were subjected to sequence and phylogenetic analyses. Based on the complete coding region, all the Indian strains clustered in the Asia topotype and exhibited a more than 11% nt divergence from the other Asian strains. The 5'-UTR of some Indian strains revealed block deletions of 43 and 86 nt corresponding to the pseudoknot region. Amino acids S44 in VP2 and F164 in VP1 were found to be the exclusive signatures for the Asia topotype. The vaccine strains differed at 65 aa positions in the capsid region, 13 of them antigenically critical. Variability at such positions is likely to affect the antigenic profile of these strains. Complete genome sequences of the vaccine strains presented here could serve as the reference for any comparative genomics in future.

  11. Propagation of the Israeli vaccine strain of Anaplasma centrale in tick cell lines.

    PubMed

    Bell-Sakyi, Lesley; Palomar, Ana M; Bradford, Emma L; Shkap, Varda

    2015-09-30

    Anaplasma centrale has been used in cattle as a live blood vaccine against the more pathogenic Anaplasma marginale for over 100 years. While A. marginale can be propagated in vitro in tick cell lines, facilitating studies on antigen production, immunisation and vector-pathogen interaction, to date there has been no in vitro culture system for A. centrale. In the present study, 25 cell lines derived from 13 ixodid tick species were inoculated with the Israeli vaccine strain of A. centrale and monitored for at least 12 weeks by microscopic examination of Giemsa-stained cytocentrifuge smears. Infection of 19 tick cell lines was subsequently attempted by transfer of cell-free supernate from vaccine-inoculated tick cells. In two separate experiments, rickettsial inclusions were detected in cultures of the Rhipicephalus appendiculatus cell line RAE25 28-32 days following inoculation with the vaccine. Presence of A. centrale in the RAE25 cells was confirmed by PCR assays targeting the 16S rRNA, groEL and msp4 genes; sequenced PCR products were 100% identical to published sequences of the respective genes in the Israeli vaccine strain of A. centrale. A. centrale was taken through three subcultures in RAE25 cells over a 30 week period. In a single experiment, the Dermacentor variabilis cell line DVE1 was also detectably infected with A. centrale 11 weeks after inoculation with the vaccine. Availability of an in vitro culture system for A. centrale in tick cells opens up the possibility of generating a safer and more ethical vaccine for bovine anaplasmosis. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Molecular characteristics of Polish field strains of Marek's disease herpesvirus isolated from vaccinated chickens

    PubMed Central

    2011-01-01

    Background Twenty-nine Marek's disease virus (MDV) strains were isolated during a 3 year period (2007-2010) from vaccinated and infected chicken flocks in Poland. These strains had caused severe clinical symptoms and lesions. In spite of proper vaccination with mono- or bivalent vaccines against Marek's disease (MD), the chickens developed symptoms of MD with paralysis. Because of this we decided to investigate possible changes and mutations in the field strains that could potentially increase their virulence. We supposed that such mutations may have been caused by recombination with retroviruses of poultry - especially reticuloendotheliosis virus (REV). Methods In order to detect the possible reasons of recent changes in virulence of MDV strains, polymerase chain reaction (PCR) analyses for meq oncogene and for long-terminal repeat (LTR) region of REV were conducted. The obtained PCR products were sequenced and compared with other MDV and REV strains isolated worldwide and accessible in the GeneBank database. Results Sequencing of the meq oncogene showed a 68 basepair insertion and frame shift within 12 of 24 field strains. Interestingly, the analyses also showed 0.78, 0.8, 0.82, 1.6 kb and other random LTR-REV insertions into the MDV genome in 28 of 29 of strains. These genetic inserts were present after passage in chicken embryo kidney cells suggesting LTR integration into a non-functional region of the MDV genome. Conclusion The results indicate the presence of a recombination between MDV and REV under field conditions in Polish chicken farms. The genetic changes within the MDV genome may influence the virus replication and its features in vivo. However, there is no evidence that meq alteration and REV insertions are related to the strains' virulence. PMID:21320336

  13. Antigen sparing with adjuvanted inactivated polio vaccine based on Sabin strains

    PubMed Central

    Westdijk, Janny; Koedam, Patrick; Barro, Mario; Steil, Benjamin P.; Collin, Nicolas; Vedvick, Thomas S.; Bakker, Wilfried A.M.; van der Ley, Peter; Kersten, Gideon

    2013-01-01

    Six different adjuvants, each in combination with inactivated polio vaccine (IPV) produced with attenuated Sabin strains (sIPV), were evaluated for their ability to enhance virus neutralizing antibody titers (VNTs) in the rat potency model. The increase of VNTs was on average 3-, 15-, 24-fold with adjuvants after one immunization (serotype 1, 2, and 3, respectively). Also after a boost immunization the VNTs of adjuvanted sIPV were on average another 7- 20- 27 times higher than after two inoculations of sIPV without adjuvant. The results indicate that it is feasible to increase the potency of inactivated polio vaccines by using adjuvants. PMID:23313617

  14. Psychological strains and suicide intent: Results from a psychological autopsy study with Chinese rural young suicides.

    PubMed

    Sun, Long; Li, Han; Zhang, Jie; Wu, Qiong

    2015-11-01

    Previous studies have examined the prevalence of psychological strains among various suicide populations. However, it is still unexamined whether psychological strains can predict suicide intent directly. We planned to explore the prevalence of psychological strains and analyze the relationship between psychological strains and suicide intent among Chinese rural young suicides. Psychological autopsy method was used to investigate the environmental and other factors of rural young suicides. Psychological strains were identified from in-depth interviews by the proxy informants of each suicide. The first 8 items of Beck's Suicidal Intention Scale (SIS) were used to estimate the suicide intent. Results showed that 96.6% of the suicides had at least one type of strain, and those suicides who had more strains tended to score higher on the suicide intent scale. The study further supports that suicide intent can be predicted by psychological strains in Chinese rural young suicides. The scanning of psychological strains can be used for suicide prevention in Chinese rural young suicides. © The Author(s) 2015.

  15. Genotype analysis of ORF 62 identifies varicella-zoster virus infections caused by a vaccine strain in children.

    PubMed

    Kwak, Byung Ok; Lee, Hoan Jong; Kang, Hyun Mi; Oh, Chi Eun; Choi, Eun Hwa

    2017-02-15

    This study was performed to differentiate vaccine-type strains from wild-type strains and determine the genotype of varicella-zoster virus (VZV) in 51 Korean children. A sequencing analysis of ORF 62 identified two cases of herpes zoster caused by the vaccine-type virus, without a previous history of varicella, 22 months and 5 months after VZV vaccination. The wild-type strain was identified in the remaining children. A genotype analysis of ORF 22 amino acids revealed genotype J in all children except one. Genotype E was identified in an infant with varicella imported from Egypt.

  16. High definition viral vaccine strain identity and stability testing using full-genome population data--The next generation of vaccine quality control.

    PubMed

    Höper, Dirk; Freuling, Conrad M; Müller, Thomas; Hanke, Dennis; von Messling, Veronika; Duchow, Karin; Beer, Martin; Mettenleiter, Thomas C

    2015-10-26

    Vaccines are the most effective prophylactic public health tools. With the help of vaccines, prevention of infectious disease spread and, in concert with other measures, even eradication has become possible. Until now, licensing and quality control require the determination of consensus genome sequences of replication competent infectious agents contained in vaccines. Recent improvements in sequencing technologies now enable the sequencing of complete genomes and the genetic analysis of populations with high reliability and resolution. The latter is particularly important for RNA viruses, which consist of fluctuating heterogeneous populations rather than genetically stable entities. This information now has to be integrated into the existing regulatory framework, challenging both licensing authorities and vaccine producers to develop new quality control criteria. Commercially available modified-live oral rabies vaccines and their precursor strains were deep-sequenced to assess strain identity and relations between strains based on population diversity. Strain relations were inferred based on the Manhattan distances calculated between the compositions of the viral populations of the strains. We provide a novel approach to assess viral strain relations with high resolution and reliability by deep sequencing with subsequent analysis of the overall genetic diversity within the viral populations. A comparison of our novel approach of inferring strain relations based on population data with consensus sequence analysis clearly shows that consensus sequence analysis of diverse viral populations can be misleading. Therefore, for quality control of viral vaccines deep sequencing analysis is to be preferred over consensus sequence analysis. The presented methodology allows for routine integration of deep sequencing data in vaccine quality control and licensing for highly reliable assessment of strain identity and stability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Possible outcomes of reassortment in vivo between wild type and live attenuated influenza vaccine strains.

    PubMed

    Kiseleva, Irina; Dubrovina, Irina; Bazhenova, Ekaterina; Fedorova, Ekaterina; Larionova, Natalie; Rudenko, Larisa

    2012-12-07

    Reassortment of influenza viruses in nature has been well documented. Genetic reassortment plays a key role in emergence of new influenza A strains, including pandemic viruses. Permissive host can be simultaneously coinfected with multiple influenza viruses. During genetic reassortment gene segments are exchanged between parental viruses that may lead to some enhancement of virulence of reassortant progeny. At present, vaccination with live attenuated cold-adapted (ca) reassortant vaccine (LAIV) is used as an effective public health measure for influenza prophylaxis. However, there are concerns about a potential of simultaneous infection of human host with ca and wild type (wt) influenza viruses which might produce progeny that contain novel, more virulent genotypes. The aim of this study was to investigate potential consequences of reassortment of wt with LAIV strains in vivo. We demonstrated that reassortment of wt viruses with ca strains in guinea pigs have resulted in progeny virus which caused reduced macroscopic lesions of chicken embryos. According to phenotypical data 95% (19 out of 20) isolated reassortants were restricted in replication at elevated temperature of 40°C. None of reassortants were more virulent than wt parents, or revealed significantly higher macroscopic lesions than wt parental viruses. Our results suggest that genetic reassortment between wt and vaccine strain is unlikely to lead to virulent reassortant progeny. These findings provide additional support of LAIV safety data. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Influenza vaccine effectiveness estimates for Western Australia during a period of vaccine and virus strain stability, 2010 to 2012.

    PubMed

    Levy, Avram; Sullivan, Sheena G; Tempone, Simone S; Wong, Kerry L M; Regan, Annette K; Dowse, Gary K; Effler, Paul V; Smith, David W

    2014-10-29

    During 2010-2012 the strain composition of the influenza vaccine in the Southern Hemisphere did not change, but the circulating virus type/subtype did. We pooled data for these years from the Western Australian sentinel medical practice surveillance system for influenza to estimate vaccine effectiveness (VE) by influenza virus type and subtype. A case test-negative design was used with VE estimated as (1-odds ratio)×100%. There were 2182 patients included in the analysis across the 3 years studied. The predominant subtype was A/H1pdm09 in 2010 and 2011, and A/H3 in 2012. The overall adjusted VE estimate against all influenza for 2010-2012 was 51% (95% CI: 36, 63). Estimates were highest against A/H1pdm09 at 74% (95% CI: 47, 87), followed by 56% (95% CI: 33, 71) for influenza B and lowest against A/H3 at 39% (95% CI: 13, 57). When analyses were restricted to compare influenza-positive patients with patients who tested positive for a non-influenza virus, overall adjusted VE was 59% (95% CI: 39, 72). These results suggest moderate protection against influenza by vaccination in Western Australia over the period 2010-2012, and are consistent with findings from other settings.

  19. A novel sequence-based antigenic distance measure for H1N1, with application to vaccine effectiveness and the selection of vaccine strains

    PubMed Central

    Pan, Keyao; Subieta, Krystina C.; Deem, Michael W.

    2011-01-01

    H1N1 influenza causes substantial seasonal illness and was the subtype of the 2009 influenza pandemic. Precise measures of antigenic distance between the vaccine and circulating virus strains help researchers design influenza vaccines with high vaccine effectiveness. We here introduce a sequence-based method to predict vaccine effectiveness in humans. Historical epidemiological data show that this sequence-based method is as predictive of vaccine effectiveness as hemagglutination inhibition assay data from ferret animal model studies. Interestingly, the expected vaccine effectiveness is greater against H1N1 than H3N2, suggesting a stronger immune response against H1N1 than H3N2. The evolution rate of hemagglutinin in H1N1 is also shown to be greater than that in H3N2, presumably due to greater immune selection pressure. PMID:21123189

  20. Efficacy of one dose vaccination against experimental infection with two Mycoplasma hyopneumoniae strains.

    PubMed

    Michiels, Annelies; Arsenakis, Ioannis; Boyen, Filip; Krejci, Roman; Haesebrouck, Freddy; Maes, Dominiek

    2017-08-29

    Mycoplasma hyopneumoniae (M. hyopneumoniae) is the primary agent of enzootic pneumonia in pigs. Pigs are often infected with different M. hyopneumoniae strains. This study assessed the efficacy of vaccination against experimental infection with two genetically different M. hyopneumoniae strains in weaned piglets. At 33 days of age (D0), 45 M. hyopneumoniae-free piglets were randomly assigned to three different groups: 1) negative control group (NCG; n = 5): not vaccinated, not infected, 2) positive control group (PCG; n = 20): not vaccinated, infected, and 3) vaccination group (VG; n = 20): single vaccination with an inactivated whole-cell M. hyopneumoniae vaccine (Hyogen®, Ceva) (D1), infected. The PCG and VG were endotracheally inoculated with 7 × 10(7) CCU in 7 ml of the highly virulent M. hyopneumoniae strain F7.2C (D24) and 7 × 10(7) CCU in 7 ml low virulent strain F1.12A (D25). A respiratory disease score (RDS) was assessed from D24 until D53. At D53 (euthanasia), macroscopic lung lesions (MLL) were scored, log copies of M. hyopneumoniae DNA (qPCR) and IL-1 and IL-6-concentrations (ELISA) on bronchoalveolar lavage fluid were determined. The RDS and MLL at euthanasia were respectively 0, 1.20 and 0.55 (P < 0.001) and 0, 7.56 and 0.68 (P < 0.001) for NCG, PCG and VG, respectively. The qPCR results for PCG and VG were 3.99 and 1.78 log copies (P < 0.001), respectively, with a significant difference between PCG and VG. The IL-1 and IL-6 results at euthanasia for NCG, PCG and VG were 17.61, 1283.39 and 53.04 pg/ml (P < 0.001) and 148.10, 493.35 and 259.80 pg/ml (P = 0.004), respectively with a significant difference between PCG and VG. Vaccination with Hyogen® in pigs was efficacious against an experimental challenge with both a low and highly virulent M. hyopneumoniae strain as the vaccinated pigs coughed significantly less, and showed significantly less lung lesions compared to the non-vaccinated challenged pigs: the vaccinated

  1. Vector Development for the Expression of Foreign Proteins in the Vaccine Strain Brucella abortus S19

    PubMed Central

    Comerci, Diego J.; Pollevick, Guido D.; Vigliocco, Ana M.; Frasch, Alberto C. C.; Ugalde, Rodolfo A.

    1998-01-01

    A vector for the expression of foreign antigens in the vaccine strain Brucella abortus S19 was developed by using a DNA fragment containing the regulatory sequences and the signal peptide of the Brucella bcsp31 gene. This fragment was cloned in broad-host-range plasmid pBBR4MCS, resulting in plasmid pBEV. As a reporter protein, a repetitive antigen of Trypanosoma cruzi was used. The recombinant fusion protein is stably expressed and secreted into the Brucella periplasmic space, inducing a good antibody response against the T. cruzi antigen. The expression of the repetitive antigen in Brucella neither altered its growth pattern nor generated a toxic or lethal effect during experimental infection. The application of this strategy for the generation of live recombinant vaccines and the tagging of B. abortus S19 vaccine is discussed. This is the first time that a recombinant protein has been expressed in the periplasm of brucellae. PMID:9673273

  2. Antibody Response from Whole-Cell Pertussis Vaccine Immunized Brazilian Children against Different Strains of Bordetella pertussis

    PubMed Central

    Pereira, Alexandre; Pietro Pereira, Aparecida S.; Silva, Célio Lopes; de Melo Rocha, Gutemberg; Lebrun, Ivo; Sant'Anna, Osvaldo A.; Tambourgi, Denise V.

    2010-01-01

    Bordetella pertussis is a gram-negative bacillus that causes the highly contagious disease known as pertussis or whooping cough. Antibody response in children may vary depending on the vaccination schedule and the product used. In this study, we have analyzed the antibody response of cellular pertussis vaccinated children against B. pertussis strains and their virulence factors, such as pertussis toxin, pertactin, and filamentous hemagglutinin. After the completion of the immunization process, according to the Brazilian vaccination program, children serum samples were collected at different periods of time, and tested for the presence of specific antibodies and antigenic cross-reactivity. Results obtained show that children immunized with three doses of the Brazilian whole-cell pertussis vaccine present high levels of serum antibodies capable of recognizing the majority of the components present in vaccinal and non-vaccinal B. pertussis strains and their virulence factors for at least 2 years after the completion of the immunization procedure. PMID:20348518

  3. A pilot study comparing the development of EIAV Env-specific antibodies induced by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine.

    PubMed

    Meng, Qinglai; Lin, Yuezhi; Ma, Jian; Ma, Yan; Zhao, Liping; Li, Shenwei; Yang, Kai; Zhou, Jianhua; Shen, Rongxian; Zhang, Xiaoyan; Shao, Yiming

    2012-12-01

    Data from successful attenuated lentiviral vaccine studies indicate that fully mature Env-specific antibodies characterized by high titer, high avidity, and the predominant recognition of conformational epitopes are associated with protective efficacy. Although vaccination with a DNA prime/recombinant vaccinia-vectored vaccine boost strategy has been found to be effective in some trials with non-human primate/simian/human immunodeficiency virus (SHIV) models, it remains unclear whether this vaccination strategy could elicit mature equine infectious anemia virus (EIAV) Env-specific antibodies, thus protecting vaccinated horses against EIAV infection. Therefore, in this pilot study we vaccinated horses using a strategy based on DNA prime/recombinant Tiantan vaccinia (rTTV)-vectored vaccines encoding EIAV env and gag genes, and observed the development of Env-specific antibodies, neutralizing antibodies, and p26-specific antibodies. Vaccination with DNA induced low titer, low avidity, and the predominant recognition of linear epitopes by Env-specific antibodies, which was enhanced by boosting vaccinations with rTTV vaccines. However, the maturation levels of Env-specific antibodies induced by the DNA/rTTV vaccines were significantly lower than those induced by the attenuated vaccine EIAV(FDDV). Additionally, DNA/rTTV vaccines did not elicit broadly neutralizing antibodies. After challenge with a virulent EIAV strain, all of the vaccinees and control horses died from EIAV disease. These data indicate that the regimen of DNA prime/rTTV vaccine boost did not induce mature Env-specific antibodies, which might have contributed to immune protection failure.

  4. A Pilot Study Comparing the Development of EIAV Env-Specific Antibodies Induced by DNA/Recombinant Vaccinia-Vectored Vaccines and an Attenuated Chinese EIAV Vaccine

    PubMed Central

    Meng, Qinglai; Lin, Yuezhi; Ma, Jian; Ma, Yan; Zhao, Liping; Li, Shenwei; Yang, Kai; Zhou, Jianhua; Shen, Rongxian

    2012-01-01

    Abstract Data from successful attenuated lentiviral vaccine studies indicate that fully mature Env-specific antibodies characterized by high titer, high avidity, and the predominant recognition of conformational epitopes are associated with protective efficacy. Although vaccination with a DNA prime/recombinant vaccinia-vectored vaccine boost strategy has been found to be effective in some trials with non-human primate/simian/human immunodeficiency virus (SHIV) models, it remains unclear whether this vaccination strategy could elicit mature equine infectious anemia virus (EIAV) Env-specific antibodies, thus protecting vaccinated horses against EIAV infection. Therefore, in this pilot study we vaccinated horses using a strategy based on DNA prime/recombinant Tiantan vaccinia (rTTV)-vectored vaccines encoding EIAV env and gag genes, and observed the development of Env-specific antibodies, neutralizing antibodies, and p26-specific antibodies. Vaccination with DNA induced low titer, low avidity, and the predominant recognition of linear epitopes by Env-specific antibodies, which was enhanced by boosting vaccinations with rTTV vaccines. However, the maturation levels of Env-specific antibodies induced by the DNA/rTTV vaccines were significantly lower than those induced by the attenuated vaccine EIAVFDDV. Additionally, DNA/rTTV vaccines did not elicit broadly neutralizing antibodies. After challenge with a virulent EIAV strain, all of the vaccinees and control horses died from EIAV disease. These data indicate that the regimen of DNA prime/rTTV vaccine boost did not induce mature Env-specific antibodies, which might have contributed to immune protection failure. PMID:23171359

  5. B-cell responses after intranasal vaccination with the novel attenuated Bordetella pertussis vaccine strain BPZE1 in a randomized phase I clinical trial.

    PubMed

    Jahnmatz, Maja; Amu, Sylvie; Ljungman, Margaretha; Wehlin, Lena; Chiodi, Francesca; Mielcarek, Nathalie; Locht, Camille; Thorstensson, Rigmor

    2014-06-05

    Despite high vaccination coverage, pertussis is still a global concern in infant morbidity and mortality, and improved pertussis vaccines are needed. A live attenuated Bordetella pertussis strain, named BPZE1, was designed as an intranasal vaccine candidate and has recently been tested in man in a phase I clinical trial. Here, we report the evaluation of the B-cell responses after vaccination with BPZE1. Forty-eight healthy males with no previous pertussis-vaccination were randomized into one of three dose-escalating groups or into a placebo group. Plasma blast- and memory B-cell responses were evaluated by ELISpot against three different pertussis antigens: pertussis toxin, filamentous haemagglutinin and pertactin. Seven out of the 36 subjects who had received the vaccine were colonized by BPZE1, and significant increases in the memory B-cell response were detected against all three tested antigens in the culture-positive subjects between days 0 and 28 post-vaccination. The culture-positive subjects also mounted a significant increase in the filamentous haemagglutinin-specific plasma blast response between days 7 and 14 post-vaccination. No response could be detected in the culture-negatives or in the placebo group post-vaccination. These data show that BPZE1 is immunogenic in humans and is therefore a promising candidate for a novel pertussis vaccine. This trial is registered at ClinicalTrials.gov (NCT01188512).

  6. Hepatitis C Genotype 1 Mosaic Vaccines Are Immunogenic in Mice and Induce Stronger T-Cell Responses than Natural Strains

    PubMed Central

    Dilan, Rebecca; Borducchi, Erica; Stanley, Kelly; Giorgi, Elena; Fischer, William; Theiler, James; Marcotrigiano, Joseph; Korber, Bette; Barouch, Dan H.

    2013-01-01

    Despite improved hepatitis C virus (HCV) treatments, vaccines remain an effective and economic option for curtailing the epidemic. Mosaic protein HCV genotype 1 vaccine candidates designed to address HCV diversity were immunogenic in mice. They elicited stronger T-cell responses to NS3-NS4a and E1-E2 proteins than did natural strains, as assessed with vaccine-matched peptides. PMID:23221002

  7. Emergence of mosaic recombinant strains potentially associated with vaccine JXA1-R and predominant circulating strains of porcine reproductive and respiratory syndrome virus in different provinces of China.

    PubMed

    Zhao, Huajian; Han, Qinggong; Zhang, Lei; Zhang, Zhiyong; Wu, Yufeng; Shen, Hong; Jiang, Ping

    2017-04-04

    Porcine reproductive and respiratory syndrome virus (PRRSV) has caused several outbreaks in China since 2006. However, the genetic diversity of PRRSV in China has greatly increased by rapid evolution or recombination events. Modified live-attenuated vaccines are widely used to control this disease worldwide. Although the risk and inefficacy of the vaccine has been reported, the genetic diversity between epidemic field strains and vaccine strains in China has not been completely elucidated. A total of 293 clinical samples were collected from 72 pig farms in 16 provinces of China in 2015 for PRRSV detection. A total of 28 infected samples collected from 24 pig farms in nine provinces were further selected for immunohistochemical analysis and whole genome sequencing of PRRSV. Phylogenetic analysis and recombination screening were performed with the full genome sequences of the 28 strains and other 623 reference sequences of PRRSV. Of 293 clinical samples, 117 (39.93%) were positive for PRRSV by RT-PCR. Phylogenetic results showed that the 28 strains were nested into sublineage 10.5 (classic highly pathogenic [HP]-PRRSV), sublineage 10.6 (HP-PRRSV-like strains and related recombinants), sublineage 10.7 (potential vaccine JXA1-R-like strains), and lineage 9 (NADC30-like strains and recombinants of NADC30-like strains), respectively, suggesting that multiple subgenotypes of PRRSV currently circulate in China. Recombination analyses showed that nine of 28 isolates and one isolate from other laboratory were potential complicated recombinants between the vaccine JXA1-R-like strains and predominant circulating strains. These results indicated an increase in recombination rates of PRRSV under current vaccination pressure and a more pressing situation for PRRSV eradication and control in China.

  8. Immunogenicity and safety of three 2010-2011 seasonal trivalent influenza vaccines in Chinese toddlers, children and older adults: a double-blind and randomized trial.

    PubMed

    Luo, Feng-Ji; Yang, Li-Qing; Ai, Xing; Bai, Yun-Hua; Wu, Jiang; Li, Shu-Ming; Zhang, Zheng; Lu, Min; Li, Li; Wang, Zhao-Yun; Shi, Nian-Min

    2013-08-01

    The 2009 influenza A(H1N1) pandemic strain was for the first time included in the 2010-2011 seasonal trivalent influenza vaccine (TIV). We conducted a double-blind, randomized trial in Chinese population to assess the immunogenicity and safety of the 2010-2011 TIV manufactured by GlaxoSmithKline and compared it with the counterpart vaccines manufactured by Sanofi Pasteur and Sinovac Biotech. Healthy toddlers (6-36 mo), children (6-12 y) and older adults (≥60 y) with 300 participants in each age group were enrolled to randomly receive two doses (toddlers, 28 d apart) or one dose (children and older adults). The immunogenicity was assessed by hemagglutination-inhibition (HI) assay. The solicited injection-site and systemic adverse events (AEs) were collected within 7 d after vaccination. All the three TIVs were well-tolerated with 15.1% of participants reporting AEs, most of which were mild. No serious AEs and unusual AEs were reported. Fever and pain were the most common systemic and injection-site AEs, respectively. The three TIVs showed good immunogenicity. The seroprotection rates against both H1N1 and H3N2 strains were more than 87% in toddlers after two doses and more than 95% in children and more than 86% in older adults after one dose. The seroprotection rates against B strain were 68-71% in toddlers after two doses, 70-74% in children and 69-72% in older adults after one dose. In conclusion, the three 2010-2011 TIVs had good immunogenicity and safety in Chinese toddlers, children and older adults and were generally comparable in immunogenicity and reactogenicity.

  9. The effects of strain heterology on the epidemiology of equine influenza in a vaccinated population.

    PubMed Central

    Park, A. W.; Wood, J. L. N.; Daly, J. M.; Newton, J. R.; Glass, K.; Henley, W.; Mumford, J. A.; Grenfell, B. T.

    2004-01-01

    We assess the effects of strain heterology (strains that are immunologically similar but not identical) on equine influenza in a vaccinated population. Using data relating to individual animals, for both homologous and heterologous vaccinees, we estimate distributions for the latent and infectious periods, quantify the risk of becoming infected in terms of the quantity of cross-reactive antibodies to a key surface protein of the virus (haemagglutinin) and estimate the probability of excreting virus (i.e. becoming infectious) given that infection has occurred. The data suggest that the infectious period, the risk of becoming infected (for a given vaccine-induced level of cross-reactive antibodies) and the probability of excreting virus are increased for heterologously vaccinated animals when compared with homologously vaccinated animals. The data are used to parameterize a modified susceptible, exposed, infectious and recovered/resistant (SEIR) model, which shows that these relatively small differences combine to have a large effect at the population level, where populations of heterologous vaccinees face a significantly increased risk of an epidemic occurring. PMID:15306299

  10. A national reference for inactivated polio vaccine derived from Sabin strains in Japan.

    PubMed

    Shirato, Haruko; Someya, Yuichi; Ochiai, Masaki; Horiuchi, Yoshinobu; Takahashi, Motohide; Takeda, Naokazu; Wakabayashi, Kengo; Ouchi, Yasumitsu; Ota, Yoshihiro; Tano, Yoshio; Abe, Shinobu; Yamazaki, Shudo; Wakita, Takaji

    2014-09-08

    As one aspect of its campaign to eradicate poliomyelitis, the World Health Organization (WHO) has encouraged development of the inactivated polio vaccine (IPV) derived from the Sabin strains (sIPV) as an option for an affordable polio vaccine, especially in low-income countries. The Japan Poliomyelitis Research Institute (JPRI) inactivated three serotypes of the Sabin strains and made sIPV preparations, including serotypes 1, 2 and 3 D-antigens in the ratio of 3:100:100. The National Institute of Infectious Diseases, Japan, assessed the immunogenic stability of these sIPV preparations in a rat potency test, according to an evaluation method recommended by the WHO. The immunogenicity of the three serotypes was maintained for at least 4 years when properly stored under -70°C. Based on these data, the sIPV preparations made by JPRI have been approved as national reference vaccines by the Japanese national control authority and used for the quality control of the tetracomponent sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines that were licensed for a routine polio immunization in Japan. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders

    PubMed Central

    Hatcher, Christopher L.; Mott, Tiffany M.; Muruato, Laura A.; Sbrana, Elena

    2016-01-01

    Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain. PMID:27271739

  12. Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: beginning of epidemic control.

    PubMed

    Thornton, V; Lennon, D; Rasanathan, K; O'Hallahan, J; Oster, P; Stewart, J; Tilman, S; Aaberge, I; Feiring, B; Nokleby, H; Rosenqvist, E; White, K; Reid, S; Mulholland, K; Wakefield, M J; Martin, D

    2006-02-27

    As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.

  13. [Isolation of a strain from the Bataviae pathogenic complex in patient vaccinated against copenhageni, canicola and mozdok].

    PubMed

    Alfonso, Hildefonso Cabezas; Gómez, Omar Cabezas; Fonte, Laura Marta Bencomo; Quintana, Quintana Pérez

    2005-01-01

    A Leptospira strain was isolated from a hemoculture of a patient admitted with suspicion of leptospirosis that had been previously vaccinated. It corresponded to the Bataviae pathogenic complex. This result shows that there exists immunogenic specificity and that other serogroups should be incorporated to the current vaccine.

  14. Persistent Bordetella bronchiseptica pneumonia in an immunocompetent infant and genetic comparison of clinical isolates with kennel cough vaccine strains.

    PubMed

    Rath, Barbara A; Register, Karen B; Wall, Jeffrey; Sokol, Dawn M; Van Dyke, Russell B

    2008-03-15

    An infant who experienced recurrent episodes of respiratory failure received a diagnosis of pertussis on the basis of immunofluorescence testing, but culture revealed macrolide-resistant Bordetella bronchiseptica. Genetic analysis demonstrated that the child was not infected with a kennel cough vaccine strain, although the family's dog had recently been vaccinated. The infection cleared with imipenem therapy.

  15. Establishing the 1st Chinese National Standard for inactivated hepatitis A vaccine.

    PubMed

    Gao, Fan; Mao, Qun-Ying; Wang, Yi-Ping; Chen, Pan; Liang, Zheng-Lun

    2016-07-01

    A reference standard calibrated in the International Units is needed for the quality control of hepatitis A vaccine. Thus, National Institutes for Food and Drug Control launched a project to establish a non-adsorbed inactivated hepatitis A vaccine reference as the working standard calibrated against the 1st International Standard (IS). Two national standard candidates (NSCs) were obtained from two manufacturers, and designated as NSC A (lyophilized form) and NSC B (liquid form). Six laboratories participated in the collaborative study and were asked to use their in-house validated enzyme-linked immunosorbent assay methods to detect hepatitis A vaccine antigen content. Although both exhibited good parallelism and linear relationship with IS, NSC B showed a better agreement among laboratories than NSC A. And based on suitability of the candidates, NSC B was selected. The accelerated degradation study showed that NSC B was stable at the storage temperature (≤-70 °C). Therefore NSC B was approved as the first Chinese national antigen standard for inactivated hepatitis A vaccine, with an assigned antigen content of 70 IU/ml.

  16. Some results of the work on mass immunization in the Soviet Union with live poliovirus vaccine prepared from Sabin strains*

    PubMed Central

    Chumakov, M. P.; Voroshilova, M. K.; Drozdov, S. G.; Dzagurov, S. G.; Lashkevich, V. A.; Mironova, L. L.; Ralph, N. M.; Gagarina, A. V.; Ashmarina, E. E.; Shirman, G. A.; Fleer, G. P.; Tolskaya, E. A.; Sokolova, I. S.; Elbert, L. B.; Sinyak, K. M.

    1961-01-01

    In the course of campaigns for the mass immunization of large segments of the population of the Soviet Union with live poliovirus vaccine prepared in the USSR from attenuated Sabin strains, some 15 200 000 persons received oral vaccine in 1959 and over 77 478 800 persons (mainly between 2 months and 20 years old) in 1960. Approximately 95% of these were given the vaccine incorporated in dragées. The present paper gives data on the safety and immunological activity of the live vaccine, on virus carriage and transmission of the vaccine virus to contacts, and on virus interference. In a comparison between poliomyelitis incidence in 1960 in regions where mass live vaccine immunization had been carried out and the incidence in areas where inactivated Salk vaccine was used in 1958-60, it is shown that, while the Salk vaccine did not fundamentally influence the epidemic process, the Sabin live vaccine brought about a sharp reduction in incidence and prevented the usual summer-autumn rise in the number of poliomyelitis cases. It is concluded from the two years' experience in the mass use of live vaccine from Sabin strains that poliomyelitis epidemics can be prevented. PMID:13879389

  17. Effects of value strains on psychopathology of Chinese rural youths.

    PubMed

    Zhang, Jie; Zhao, Sibo

    2013-12-01

    The Strain Theory of Suicide postulates that psychological strains usually precede mental disorders including suicidal behavior. This paper focuses on the effect of conflicting social value strains on the individual's psychopathology. We analyzed the data of 2031 respondents who were proxy informants for suicides and community living controls in a large scale psychological autopsy study in rural China, with the CES-D depression measure for the psychopathology. Individuals having experienced value conflicts between Confucian gender role and gender equalitarianism in modern society scored on depression significantly higher than the individuals who do not experience the value conflict, and it is also true when several other relevant variables were held constant in the multiple regression model. This study supports the hypotheses that people who confront value conflicts are likely to experience psychopathological strain, and the higher the level of strain, the stronger the depression.

  18. Effects of Value Strains on Psychopathology of Chinese Rural Youths

    PubMed Central

    Zhang, Jie; Zhao, Sibo

    2013-01-01

    The Strain Theory of Suicide postulates that psychological strains usually precede mental disorders including suicidal behavior. This paper focuses on the effect of conflicting social value strains on the individual’s psychopathology. We analyzed the data of 2,031 respondents who were proxy informants for suicides and community living controls in a large scale psychological autopsy study in rural China, with the CES-D depression measure for the psychopathology. Individuals having experienced value conflicts between Confucian gender role and gender equalitarianism in modern society scored on depression significantly higher than the individuals who do not experience the value conflict, and it is also true when several other relevant variables were held constant in the multiple regression model. This study supports the hypotheses that people who confront value conflicts is likely to lead to psychopathological strain, and the higher the level of strain, the stronger the depression. PMID:24309863

  19. A rapid cycleave PCR method for distinguishing the vaccine strain Brucella abortus A19 in China.

    PubMed

    Nan, Wenlong; Zhang, Yueyong; Tan, Pengfei; Xu, Zouliang; Chen, Yuqi; Mao, Kairong; Chen, Yiping

    2016-05-01

    Brucellosis is a widespread zoonotic disease caused by Brucella spp. Immunization with attenuated vaccines has proved to be an effective method of prevention; however, it may also interfere with diagnosis. Brucella abortus strain A19, which is homologous to B. abortus strain S19, is widely used for the prevention of bovine brucellosis in China. For effective monitoring of the control of brucellosis, it is essential to distinguish A19 from field strains. Single-nucleotide polymorphism-based assays offer a new approach to such discrimination studies. In the current study, we developed a cycleave PCR assay that successfully distinguished attenuated vaccine strains A19 and S19 from 22 strains of B. abortus and 57 strains of 5 other Brucella species. The assay gave a negative reaction with 4 non-Brucella species. The minimum sensitivity of the assay, evaluated using 10-fold dilutions of chromosomal DNA, was 7.6 fg for the A19 strain and 220 fg for the single non-A19/non-S19 Brucella strain tested (B. abortus 104M). The assay was also reproducible (intra- and interassay coefficients of variation: 0.003-0.01 and 0.004-0.025, respectively). The cycleave assay gave an A19/S19-specific reaction in 3 out of 125 field serum samples, with the same 3 samples being positive in an alternative A19/S19-specific molecular assay. The cycleave assay gave a total of 102 Brucella-specific reactions (3 being the A19/S19-specific reactions), whereas an alternative Brucella-specific assay gave 92 positive reactions (all also positive in the cycleave assay). Therefore, this assay represents a simple, rapid, sensitive, and specific tool for use in brucellosis control.

  20. Analysis of Spleen-Induced Fimbria Production in Recombinant Attenuated Salmonella enterica Serovar Typhimurium Vaccine Strains

    PubMed Central

    Łaniewski, Paweł; Baek, Chang-Ho; Roland, Kenneth L.

    2017-01-01

    ABSTRACT Salmonella enterica serovar Typhimurium genome encodes 13 fimbrial operons. Most of the fimbriae encoded by these operons are not produced under laboratory conditions but are likely to be synthesized in vivo. We used an in vivo expression technology (IVET) strategy to identify four fimbrial operons, agf, saf, sti, and stc that are expressed in the spleen. When any three of these operons were deleted, the strain retained wild-type virulence. However, when all four operons were deleted, the resulting strain was completely attenuated, indicating that these four fimbriae play functionally redundant roles critical for virulence. In mice, oral doses of as low as 1 × 105 CFU of the strain with four fimbrial operons deleted provided 100% protection against challenge with 1 × 109 CFU of wild-type S. Typhimurium. We also examined the possible effect of these fimbriae on the ability of a Salmonella vaccine strain to deliver a guest antigen. We modified one of our established attenuated vaccine strains, χ9088, to delete three fimbrial operons while the fourth operon was constitutively expressed. Each derivative was modified to express the Streptococcus pneumoniae antigen PspA. Strains that constitutively expressed saf or stc elicited a strong Th1 response with significantly greater levels of anti-PspA serum IgG and greater protective efficacy than strains carrying saf or stc deletions. The isogenic strain in which all four operons were deleted generated the lowest anti-PspA levels and did not protect against challenge with virulent S. pneumoniae. Our results indicate that these fimbriae play important roles, as yet not understood, in Salmonella virulence and immunogenicity. PMID:28830946

  1. High-resolution melt PCR analysis for rapid identification of Chlamydia abortus live vaccine strain 1B among C. abortus strains and field isolates.

    PubMed

    Vorimore, Fabien; Cavanna, Noémie; Vicari, Nadia; Magnino, Simone; Willems, Hermann; Rodolakis, Annie; Siarkou, Victoria I; Laroucau, Karine

    2012-09-01

    We describe a novel high-resolution melt assay that clearly differentiates Chlamydia abortus live vaccine strain 1B from field C. abortus strains and field wild-type isolates based on previously described single nucleotide polymorphisms. This modern genotyping technique is inexpensive, easy to use, and less time-consuming than PCR-RFLP.

  2. Mycoplasma gallisepticum transmission: Comparison of commercial F-strain vaccine versus layer complex-derived field strains in a tunnel ventilated house

    USDA-ARS?s Scientific Manuscript database

    Two simultaneous trials were conducted using a commercially available, live, F strain Mycoplasma gallisepticum (FMG) vaccine [Trial 1] or two inocula of layer complex-derived MG strains (LCD-MG) [Trial 2]. In each of the two trials, four commercial turkeys were housed in each of two adjoining pens ...

  3. Effects of Time-Specific F-strain Mycoplasma gallisepticum Inoculation Overlays on Prelay ts-11-strain M. gallisepticum Vaccination on Blood Characteristics of Commercial Laying Hens

    USDA-ARS?s Scientific Manuscript database

    Two trials were conducted to determine the effects of a prelay ts-11-strain Mycoplasma gallisepticum (ts-11MG) vaccination alone or in combination with subsequent time specific F-strain M. gallisepticum (FMG) inoculations on the blood characteristics of commercial laying hens. The following 4 treat...

  4. Increase in Genetic Diversity of Haemophilus influenzae Serotype b (Hib) Strains after Introduction of Hib Vaccination in The Netherlands

    PubMed Central

    Schouls, Leo M.; van der Ende, Arie; van de Pol, Ingrid; Schot, Corrie; Spanjaard, Lodewijk; Vauterin, Paul; Wilderbeek, Dorus; Witteveen, Sandra

    2005-01-01

    Recently, there has been an increase in The Netherlands in the number of cases of invasive disease caused by Haemophilus influenzae serotype b (Hib). To study a possible change in the Hib population that could explain the rise in incidence, a multiple-locus variable number tandem repeats analysis (MLVA) was developed to genotype H. influenzae isolates. The MLVA enabled the differentiation of H. influenzae serotype b strains with higher discriminatory power than multilocus sequence typing (MLST). MLVA profiles of noncapsulated H. influenzae and H. influenzae serotype f strains were more heterogeneous than serotype b strains and were distinct from Hib, although some overlap occurred. The MLVA was used to genotype a collection of 520 H. influenzae serotype b strains isolated from patients in The Netherlands with invasive disease. The strains were collected from 1983 from 2002, covering a time period of 10 years before and 9 years after the introduction of the Hib vaccine in the Dutch national vaccination program. MLVA revealed a sharp increase in genetic diversity of Hib strains isolated from neonates to 4-year-old patients after 1993, when the Hib vaccine was introduced. Hib strains isolated from patients older than 4 years in age were genetically diverse, and no significant change in diversity was seen after the introduction of the vaccine. These observations suggest that after the introduction of the Hib vaccine young children no longer constitute the reservoir for Hib and that they are infected by adults carrying genetically diverse Hib strains. PMID:15956392

  5. Complete genome analysis of three live attenuated Rinderpest virus vaccine strains derived through serial passages in different culture systems.

    PubMed

    Jeoung, Hye-Young; Lee, Myoung-Heon; Yeh, Jung-Yong; Lim, Ji-Ae; Lim, Seong-In; Oem, Jae-Ku; Song, Jae-Young; Lee, Won-Ha; Park, Jong-Hwan; An, Dong-Jun

    2012-12-01

    The genomes of three South Korean Rinderpest virus vaccine strains (L72, LA77, and LA96) were analyzed in order to investigate their genetic variability. These three vaccine strains were all derived from the same virus strain origin (Fusan) through repeated passages in different culture systems. The full genome length of the three strains was 15,882 nucleotides, and the sequence similarity between the three South Korean RPV strains at the nucleotide level was 98.1 to 98.9%. The genetic distance between Nakamura III, L72, LA77, LA96, and LATC06 and the Kabete strain was greater than that between the Fusan and Kabete strains for the P, V, and C genes. The difference in pathogenicity among these strains might be due to the V gene, which has a positive (>1) selection ratio based on the analysis of synonymous (dS) and nonsynonymous (dN) substitution rates (dN/dS ratio [ω]).

  6. Antibody responses of Macaca fascicularis against a new inactivated polio vaccine derived from Sabin strains (sIPV) in DTaP-sIPV vaccine.

    PubMed

    Sato, Y; Shiosaki, K; Goto, Y; Sonoda, K; Kino, Y

    2013-05-01

    Antibody responses of Macaca fascicularis against a new tetravalent vaccine composed of diphtheria toxoid, tetanus toxoid, acellular pertussis antigens, and inactivated poliovirus derived from Sabin strains (sIPV) was investigated to predict an optimal dose of sIPV in a new tetravalent vaccine (DTaP-sIPV) prior to conducting a dose-defined clinical study. Monkeys were inoculated with DTaP-sIPVs containing three different antigen units of sIPVs: Vaccine A (types 1:2:3 = 3:100:100 DU), Vaccine B (types 1:2:3 = 1.5:50:50 DU), and Vaccine C (types 1:2:3 = 0.75:25:25 DU). There was no difference in the average titers of neutralizing antibody against the attenuated or virulent polioviruses between Vaccines A and B. The average neutralizing antibody titers of Vaccine C tended to be lower than those of Vaccines A and B. The sIPV antigens did not affect the anti-diphtheria or anti-tetanus antibody titers of DTaP-sIPV. Furthermore, the average neutralizing antibody titers of Vaccine A against the attenuated and virulent polioviruses were comparable between M. fascicularis and humans. These results suggest that M. fascicularis may be a useful animal model for predicting the antibody responses to sIPVs in humans, and that it may be likely to reduce the amount of sIPVs contained in DTaP-sIPVs, even for humans.

  7. Simple differentiation method of mumps Hoshino vaccine strain from wild strains by reverse transcription loop-mediated isothermal amplification (RT-LAMP).

    PubMed

    Yoshida, Naoko; Fujino, Motoko; Ota, Yoshinori; Notomi, Tsugunori; Nakayama, Tetsuo

    2007-01-26

    Mumps virus is still circulating and annual mumps outbreaks occur with fluctuating magnitudes in Japan. Aseptic meningitis has been reported after vaccination and it would be of importance to determine whether this was related to the vaccination. The objective of this study was to develop a sensitive, specific and rapid diagnostic method for the differentiation of the Hoshino vaccine strain from circulating wild types. We developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method of the hemagglutinin neuraminidase (HN) region for the detection of mumps virus genome from clinical samples. The typical ladder pattern disappeared after the LAMP products of the Hoshino vaccine strain were digested with ScaI, but those of wild types were not cut by ScaI. We obtained 19 cerebro spinal fluids (CSF) from the patients with aseptic meningitis and 17 salivary swab samples from the patients with acute parotitis after mumps vaccination, in which one case was complicated with orchitis. Mumps virus genome was detected in 18 CSF samples and in all NPS by RT-LAMP. The Hoshino vaccine strain was identified in 16 out of 18 CSF RT-LAMP positives and in 11 out of 17 NPS samples and the remaining samples were identified as wild types. RT-LAMP followed by ScaI digestion is a sensitive, simple and rapid differential method and useful for laboratory surveillance for vaccine-adverse events.

  8. Genetic and immunologic relationships between vaccine and field strains for vaccine selection of type A foot-and-mouth disease virus circulating in East Asia.

    PubMed

    Lee, Seo-Yong; Park, Min-Eun; Kim, Rae-Hyung; Ko, Mi-Kyeong; Lee, Kwang-Nyeong; Kim, Su-Mi; Shim, Hang-Sub; Kim, Byounghan; Lee, Jong-Soo; Park, Jong-Hyeon

    2015-01-29

    Of the seven known serotypes of foot-and-mouth disease virus (FMDV), type A has the most diverse variations. Genetic variations also occur frequently at VP1, VP2, VP3, and VP4 because these proteins constitute the viral capsid. The structural proteins of FMDV, which are closely related to immunologic correlations, are the most easily analyzed because they have highly accessible information. In this study we analyzed the type A vaccine viruses by alignment of available sequences in order to find appropriate vaccine strains. The matching rate of ASIA topotype-specific sites (20 amino acids) located on the viral surface, which are mainly VP1 and VP2, was highly related to immunologic reactivity. Among the available vaccines analyzed in this study, we suggest that A Malaysia 97 could be used as a vaccine virus as it has the highest genetic similarity and immunologic aspects to field strains originating in East Asia.

  9. Serological profile of buffalo (Bubalus bubalis) female calves vaccinated with standard Brucella abortus strain 19 vaccine using rose bengal, 2-mercaptoethanol and complement fixation tests.

    PubMed

    Nardi, G Júnior; Ribeiro, M G; Jorge, A M; Megid, J; Silva, L M P

    2012-03-01

    The serological profiles of 21 female buffaloes vaccinated between 3 and 8 months of age using Brucella abortus strain 19 (S19) were evaluated by rose bengal (RBT), 2-mercaptoethanol (2ME) and complement fixation (CFT) tests. The serum strains were collected in day zero, 15, 30, 45, 60th days and subsequently to each 30 months, until 720th day after vaccination. No animal showed reaction in day zero. In 15th day above 95% of animals revealed reaction in all tests. All the animals presented absence of reactions in CFT, RBT and 2ME tests at 270, 300 and 360 days after vaccination, respectively. Our finding highlighted early response in CFT compared than other conventional agglutination tests. None of animals presented oscillation of titers or reactions in any test after 360 day of study, which enables the use of these tests after this period without interference of antibodies from S19 vaccine origin between 3 and 8 months in buffalo heifers.

  10. Late Onset Hypomorphic RAG2 Deficiency Presentation with Fatal Vaccine-Strain VZV Infection.

    PubMed

    Dutmer, Cullen M; Asturias, Edwin J; Smith, Christiana; Dishop, Megan K; Schmid, D Scott; Bellini, William J; Tirosh, Irit; Lee, Yu Nee; Notarangelo, Luigi D; Gelfand, Erwin W

    2015-11-01

    Hypomorphic mutations in RAG1 and RAG2 are associated with significant clinical heterogeneity and symptoms of immunodeficiency or autoimmunity may be late in appearance. As a result, immunosuppressive medications may be introduced that can have life-threatening consequences. We describe a previously healthy 13-month-old girl presenting with rash and autoimmune hemolytic anemia, while highlighting the importance of vigilance and consideration of an underlying severe immunodeficiency disease prior to instituting immunosuppressive therapy. Given clinical deterioration of the patient and a temporal association with recently administered vaccinations, virus genotyping was carried out via 4 real-time Forster Resonance Energy Transfer PCR protocols targeting vaccine-associated single nucleotide polymorphisms. Genomic DNA was extracted from whole blood and analyzed via the next-generation sequencing method of sequencing-by-synthesis. Immune function studies included immunophenotyping of peripheral blood lymphocytes, mitogen-induced proliferation and TLR ligand-induced production of TNFα. Analysis of recombination activity of wild-type and mutant RAG2 constructs was performed. Virus genotyping revealed vaccine-strain VZV, mumps, and rubella. Next-generation sequencing identified heterozygosity for RAG2 R73H and P180H mutations. Profound lymphopenia was associated with intense corticosteroid therapy, with some recovery after steroid reduction. Residual, albeit low, RAG2 protein activity was demonstrated. Because of the association of RAG deficiency with late-onset presentation and autoimmunity, live virus vaccination and immunosuppressive therapies are often initiated and can result in negative consequences. Here, hypomorphic RAG2 mutations were linked to disseminated vaccine-strain virus infections following institution of corticosteroid therapy for autoimmune hemolytic anemia.

  11. Evaluation results of the 700 deg C Chinese strain gages

    NASA Technical Reports Server (NTRS)

    Hobart, H. F.

    1984-01-01

    There is a continuing interest and need for resistance strain gages capable of making static strain measurements on components located in the hot section of gas turbine engines. A paper by Tsen-tai Wu describes the development and evaluation of high temperature gauges fabricated from specially developed Fe-Cr-Al-V-Ti-Y alloy wire. Several of these gages and a quantity of P12-2 ceramic adhesive were purchased for evaluation. Nine members of the aircraft turbine engine community were invited to participate in an evaluation of these gages. Each participant was sent one strain gage, a small amount of ceramic adhesive, instructions for mounting the gage on a test beam, and a set of suggestions for the experiment. Data on gage factor variation with temperature, apparent strain, and drift are discussed.

  12. Evaluation results of the 700 deg C Chinese strain gages

    NASA Astrophysics Data System (ADS)

    Hobart, H. F.

    1984-10-01

    There is a continuing interest and need for resistance strain gages capable of making static strain measurements on components located in the hot section of gas turbine engines. A paper by Tsen-tai Wu describes the development and evaluation of high temperature gauges fabricated from specially developed Fe-Cr-Al-V-Ti-Y alloy wire. Several of these gages and a quantity of P12-2 ceramic adhesive were purchased for evaluation. Nine members of the aircraft turbine engine community were invited to participate in an evaluation of these gages. Each participant was sent one strain gage, a small amount of ceramic adhesive, instructions for mounting the gage on a test beam, and a set of suggestions for the experiment. Data on gage factor variation with temperature, apparent strain, and drift are discussed.

  13. Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection.

    PubMed

    Lyke, Kirsten E; Ishizuka, Andrew S; Berry, Andrea A; Chakravarty, Sumana; DeZure, Adam; Enama, Mary E; James, Eric R; Billingsley, Peter F; Gunasekera, Anusha; Manoj, Anita; Li, Minglin; Ruben, Adam J; Li, Tao; Eappen, Abraham G; Stafford, Richard E; Kc, Natasha; Murshedkar, Tooba; Mendoza, Floreliz H; Gordon, Ingelise J; Zephir, Kathryn L; Holman, LaSonji A; Plummer, Sarah H; Hendel, Cynthia S; Novik, Laura; Costner, Pamela J M; Saunders, Jamie G; Berkowitz, Nina M; Flynn, Barbara J; Nason, Martha C; Garver, Lindsay S; Laurens, Matthew B; Plowe, Christopher V; Richie, Thomas L; Graham, Barney S; Roederer, Mario; Sim, B Kim Lee; Ledgerwood, Julie E; Hoffman, Stephen L; Seder, Robert A

    2017-02-21

    A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 10(5) PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls (P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.

  14. Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection

    PubMed Central

    Lyke, Kirsten E.; Berry, Andrea A.; Chakravarty, Sumana; DeZure, Adam; Enama, Mary E.; James, Eric R.; Billingsley, Peter F.; Gunasekera, Anusha; Manoj, Anita; Li, Minglin; Ruben, Adam J.; Li, Tao; Eappen, Abraham G.; Stafford, Richard E.; KC, Natasha; Murshedkar, Tooba; Mendoza, Floreliz H.; Gordon, Ingelise J.; Zephir, Kathryn L.; Holman, LaSonji A.; Plummer, Sarah H.; Hendel, Cynthia S.; Novik, Laura; Costner, Pamela J. M.; Saunders, Jamie G.; Berkowitz, Nina M.; Flynn, Barbara J.; Nason, Martha C.; Garver, Lindsay S.; Laurens, Matthew B.; Plowe, Christopher V.; Richie, Thomas L.; Graham, Barney S.; Roederer, Mario; Sim, B. Kim Lee; Ledgerwood, Julie E.; Hoffman, Stephen L.; Seder, Robert A.

    2017-01-01

    A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 105 PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35–87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls (P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36–99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations. PMID:28223498

  15. ENHANCED IMMUNE RESPONSE OF RED DEER (CERVUS ELAPHUS) TO LIVE RB51 VACCINE STRAIN USING COMPOSITE MICROSPHERES

    PubMed Central

    Arenas-Gamboa, Angela M.; Ficht, Thomas A.; Davis, Donald S.; Elzer, Philip H.; Wong-Gonzalez, Alfredo; Rice-Ficht, Allison C.

    2012-01-01

    Brucellosis is an important zoonotic disease of nearly worldwide distribution. The occurrence of the infection in humans is largely dependent on the prevalence of brucellosis in animal reservoirs, including wildlife. The current vaccine used for cattle Brucella abortus strain RB51, has proven ineffective in protecting bison (Bison bison) and elk (Cervus nelsoni) from infection and abortion. To test possible improvements in vaccine efficacy, a novel approach of immunization was examined from April 2004 to November 2006 using alginate composite microspheres containing a nonimmunogenic, eggshell-precursor protein of the parasite Fasciola hepatica (Vitelline protein B, VpB) to deliver live vaccine strain RB51. Red deer (Cervus elaphus), used as a model for elk, were vaccinated orally (PO) or subcutaneously (SC) with 1.5×1010 viable organisms per animal. Humoral responses postvaccination (immunoglobulin G [IgG] levels), assessed at different time points, indicated that capsules containing live RB51 elicited an anti-Brucella specific IgG response. Furthermore, the encapsulated vaccine elicited a cell-mediated response that the nonencapsulated vaccinates failed to produce. Finally, red deer were challenged with B. abortus strain 19 by conjunctival exposure. Only animals that received encapsulated RB51 vaccine by either route exhibited a significant reduction in bacterial counts in their spleens. These data suggest that alginate-VpB microspheres provide a method to enhance the RB51 vaccine performance in elk. PMID:19204345

  16. Evaluation of Factors Influencing Efficacy of Vaccine Strain CVI988 Against Marek's Disease in Meat-Type Chickens.

    PubMed

    Gimeno, Isabel M; Cortes, Aneg L; Faiz, Nik M; Barbosa, Taylor; Villalobos, Tarsicio

    2015-09-01

    Marek's disease (MD) strain CVI988 is the most-protective commercially available vaccine against very virulent plus (vv+) Marek's disease virus (MDV). However, its use in meat-type chickens has been controversial. While several countries have been using CVI988 for more than 40 yr, others do not authorize its use or it is restricted mainly to layers. The use of CVI988 in meat-type chickens will be necessary in the future in areas where other vaccine protocols fail. The objective of this study was to evaluate factors (vaccine dose, vaccine origin, chicken genetics, age and route of vaccination, and combination with other MD vaccines) influencing the efficacy of CVI988 against MD in meat-type chickens. Three animal experiments were conducted in which various vaccine protocols using CVI988 were tested for their protection against challenge with vv+ strain 648A by contact at day of age. Experiments 1 and 2 were to compare the efficacy of CVI988 vaccines from three different origins (CVI988-A, CVI988-B, and CVI988-C) and evaluate the effect of vaccine dose and chicken genetics. Experiment 3 was to evaluate the effect of adding CVI988 vaccine to various vaccine protocols using other MD vaccines of serotypes 2 (SB-1) and 3 (rHVT). Our results show that, regardless of the origin of the vaccine, protection against early challenge with 648A was good when vaccines were administered at a high dose (>3000 plaque-forming units [PFU]). Differences among vaccines, however, were detected even when using a high dose in experiment 2 (vaccine CVI988-B conferred higher protection than did CVI988-C) but not in Experiment 1 (CVI988-B was compared to CVI988-A). The use of a fixed low dose (2000 PFU) of vaccine resulted in reduction in protection, and such reduction was more remarkable when using CV1988-A. No statistically significant differences were found when we compared the efficacy of CVI988 in two different genetic lines of broiler chickens (G1 and G2). Vaccination protocols that

  17. Protective efficacy of commercial inactivated Newcastle disease virus vaccines in chickens against a recent Korean epizootic strain.

    PubMed

    Jeon, Woo-Jin; Lee, Eun-Kyoung; Lee, Young-Jeong; Jeong, Ok-Mi; Kim, Yong-Joo; Kwon, Jun-Hun; Choi, Kang-Seuk

    2008-09-01

    Despite the intensive vaccination policy that has been put in place to control Newcastle disease virus (NDV), the recent emergence of NDV genotype VII strains in Korea has led to significant economic losses in the poultry industry. We assessed the ability of inactivated, oil-emulsion vaccines derived from La Sota or Ulster 2C NDV strains to protect chickens from challenge with Kr-005/00, which is a recently isolated Korean epizootic genotype VII strain. Six-week-old SPF chickens were vaccinated once and challenged three weeks later via the eye drop/intranasal route. All vaccinated birds were fully protected from disease, regardless of the vaccine strains used. All vaccinated and challenged groups showed significant sero-conversion 14 days after challenge. However, some vaccinated birds, despite being protected from disease, shed the challenge virus from their oro-pharynx and cloaca, albeit at significantly lower titers than the unvaccinated challenged control birds. The virological, serological, and epidemiological significance of our observations with regard to NDV disease eradication is discussed.

  18. Construction and Characterization of a Nonproliferative El Tor Cholera Vaccine Candidate Derived from Strain 638

    PubMed Central

    Valle, Edgar; Ledón, Talena; Cedré, Bárbara; Campos, Javier; Valmaseda, Tania; Rodríguez, Boris; García, Luis; Marrero, Karen; Benítez, Jorge; Rodríguez, Sandra; Fando, Rafael

    2000-01-01

    In recent clinical assays, our cholera vaccine candidate strain, Vibrio cholerae 638 El Tor Ogawa, was well tolerated and immunogenic in Cuban volunteers. In this work we describe the construction of 638T, a thymidine auxotrophic version of improved environmental biosafety. In so doing, the thyA gene from V. cholerae was cloned, sequenced, mutated in vitro, and used to replace the wild-type allele. Except for its dependence on thymidine for growth in minimal medium, 638T is essentially indistinguishable from 638 in the rate of growth and morphology in complete medium. The two strains showed equivalent phenotypes with regard to motility, expression of the celA marker, colonization capacity in the infant mouse cholera model, and immunogenicity in the adult rabbit cholera model. However, the ability of this new strain to survive environmental starvation was limited with respect to that of 638. Taken together, these results suggest that this live, attenuated, but nonproliferative strain is a new, promising cholera vaccine candidate. PMID:11035753

  19. Nanogram quantities of a DNA vaccine protect rainbow trout fry against heterologous strains of infectious hematopoietic necrosis virus

    USGS Publications Warehouse

    Corbeil, S.; LaPatra, S.E.; Anderson, E.D.; Kurath, G.

    2000-01-01

    The efficacy of a DNA vaccine containing the glycoprotein gene of infectious hematopoietic necrosis virus (IHNV), a rhabdovirus affecting trout and salmon, was investigated. The minimal dose of vaccine required, the protection against heterologous strains, and the titers of neutralizing antibodies produced were used to evaluate the potential of the vaccine as a control pharmaceutical. Results indicated that a single dose of as little as 1–10 ng of vaccine protected rainbow trout fry against waterborne challenge by IHNV. An optimal dose of 100 ng per fish was selected to assure strong protection under various conditions. Neutralizing antibody titers were detected in fish vaccinated with concentrations of DNA ranging from 5 to 0.01 μg. Furthermore, the DNA vaccine protected fish against a broad range of viral strains from different geographic locations, including isolates from France and Japan, suggesting that the vaccine could be used worldwide. A single dose of this DNA vaccine induced protection in fish at a lower dose than is usually reported in mammalian DNA vaccine studies.

  20. Comparative immunological evaluation of recombinant Salmonella Typhimurium strains expressing model antigens as live oral vaccines

    PubMed Central

    2012-01-01

    Background Despite the development of various systems to generate live recombinant Salmonella Typhimurium vaccine strains, little work has been performed to systematically evaluate and compare their relative immunogenicity. Such information would provide invaluable guidance for the future rational design of live recombinant Salmonella oral vaccines. Result To compare vaccine strains encoded with different antigen delivery and expression strategies, a series of recombinant Salmonella Typhimurium strains were constructed that expressed either the enhanced green fluorescent protein (EGFP) or a fragment of the hemagglutinin (HA) protein from the H5N1 influenza virus, as model antigens. The antigens were expressed from the chromosome, from high or low-copy plasmids, or encoded on a eukaryotic expression plasmid. Antigens were targeted for expression in either the cytoplasm or the outer membrane. Combinations of strategies were employed to evaluate the efficacy of combined delivery/expression approaches. After investigating in vitro and in vivo antigen expression, growth and infection abilities; the immunogenicity of the constructed recombinant Salmonella strains was evaluated in mice. Using the soluble model antigen EGFP, our results indicated that vaccine strains with high and stable antigen expression exhibited high B cell responses, whilst eukaryotic expression or colonization with good construct stability was critical for T cell responses. For the insoluble model antigen HA, an outer membrane expression strategy induced better B cell and T cell responses than a cytoplasmic strategy. Most notably, the combination of two different expression strategies did not increase the immune response elicited. Conclusion Through systematically evaluating and comparing the immunogenicity of the constructed recombinant Salmonella strains in mice, we identified their respective advantages and deleterious or synergistic effects. Different construction strategies were optimally

  1. Social Strain, Self-Control, and Juvenile Gambling Pathology: Evidence From Chinese Adolescents

    ERIC Educational Resources Information Center

    Cheung, Nicole W. T.

    2016-01-01

    Despite recent concerns over youthful problem gambling, few gambling studies have looked into Asian adolescent populations. This study of a stratified, random sample of high school students in Hong Kong is designed to estimate the prevalence of gambling pathology among Chinese adolescents and to examine the relationships between social strain,…

  2. Social Strain, Self-Control, and Juvenile Gambling Pathology: Evidence From Chinese Adolescents

    ERIC Educational Resources Information Center

    Cheung, Nicole W. T.

    2016-01-01

    Despite recent concerns over youthful problem gambling, few gambling studies have looked into Asian adolescent populations. This study of a stratified, random sample of high school students in Hong Kong is designed to estimate the prevalence of gambling pathology among Chinese adolescents and to examine the relationships between social strain,…

  3. In silico prediction of conserved vaccine targets in Streptococcus agalactiae strains isolated from fish, cattle, and human samples.

    PubMed

    Pereira, U P; Soares, S C; Blom, J; Leal, C A G; Ramos, R T J; Guimarães, L C; Oliveira, L C; Almeida, S S; Hassan, S S; Santos, A R; Miyoshi, A; Silva, A; Tauch, A; Barh, D; Azevedo, V; Figueiredo, H C P

    2013-08-12

    Streptococcus agalactiae (Lancefield group B; group B streptococci) is a major pathogen that causes meningoencephalitis in fish, mastitis in cows, and neonatal sepsis and meningitis in humans. The available prophylactic measures for conserving human and animal health are not totally effective and have limitations. Effective vaccines against the different serotypes or genotypes of pathogenic strains from the various hosts would be useful. We used an in silico strategy to identify conserved vaccine candidates in 15 genomes of group B streptococci strains isolated from human, bovine, and fish samples. The degree of conservation, subcellular localization, and immunogenic potential of S. agalactiae proteins were investigated. We identified 36 antigenic proteins that were conserved in all 15 genomes. Among these proteins, 5 and 23 were shared only by human or fish strains, respectively. These potential vaccine targets may help develop effective vaccines that will help prevent S. agalactiae infection.

  4. Genetic and antigenic characterisation of serotype A FMD viruses from East Africa to select new vaccine strains

    PubMed Central

    Bari, Fufa D.; Parida, Satya; Tekleghiorghis, Tesfaalem; Dekker, Aldo; Sangula, Abraham; Reeve, Richard; Haydon, Daniel T.; Paton, David J.; Mahapatra, Mana

    2014-01-01

    Vaccine strain selection for emerging foot-and-mouth disease virus (FMDV) outbreaks in enzootic countries can be addressed through antigenic and genetic characterisation of recently circulating viruses. A total of 56 serotype A FMDVs isolated between 1998 and 2012, from Central, East and North African countries were characterised antigenically by virus neutralisation test using antisera to three existing and four candidate vaccine strains and, genetically by characterising the full capsid sequence data. A Bayesian analysis of the capsid sequence data revealed the viruses to be of either African or Asian topotypes with subdivision of the African topotype viruses into four genotypes (Genotypes I, II, IV and VII). The existing vaccine strains were found to be least cross-reactive (good matches observed for only 5.4–46.4% of the sampled viruses). Three bovine antisera, raised against A-EA-2007, A-EA-1981 and A-EA-1984 viruses, exhibited broad cross-neutralisation, towards more than 85% of the circulating viruses. Of the three vaccines, A-EA-2007 was the best showing more than 90% in-vitro cross-protection, as well as being the most recent amongst the vaccine strains used in this study. It therefore appears antigenically suitable as a vaccine strain to be used in the region in FMD control programmes. PMID:25171846

  5. Genetic and antigenic characterisation of serotype A FMD viruses from East Africa to select new vaccine strains.

    PubMed

    Bari, Fufa D; Parida, Satya; Tekleghiorghis, Tesfaalem; Dekker, Aldo; Sangula, Abraham; Reeve, Richard; Haydon, Daniel T; Paton, David J; Mahapatra, Mana

    2014-10-07

    Vaccine strain selection for emerging foot-and-mouth disease virus (FMDV) outbreaks in enzootic countries can be addressed through antigenic and genetic characterisation of recently circulating viruses. A total of 56 serotype A FMDVs isolated between 1998 and 2012, from Central, East and North African countries were characterised antigenically by virus neutralisation test using antisera to three existing and four candidate vaccine strains and, genetically by characterising the full capsid sequence data. A Bayesian analysis of the capsid sequence data revealed the viruses to be of either African or Asian topotypes with subdivision of the African topotype viruses into four genotypes (Genotypes I, II, IV and VII). The existing vaccine strains were found to be least cross-reactive (good matches observed for only 5.4-46.4% of the sampled viruses). Three bovine antisera, raised against A-EA-2007, A-EA-1981 and A-EA-1984 viruses, exhibited broad cross-neutralisation, towards more than 85% of the circulating viruses. Of the three vaccines, A-EA-2007 was the best showing more than 90% in-vitro cross-protection, as well as being the most recent amongst the vaccine strains used in this study. It therefore appears antigenically suitable as a vaccine strain to be used in the region in FMD control programmes. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Inactivated West Nile Virus (WNV) vaccine, Duvaxyn WNV, protects against a highly neuroinvasive lineage 2 WNV strain in mice.

    PubMed

    Venter, Marietjie; van Vuren, Petrus Janse; Mentoor, Juliet; Paweska, Janusz; Williams, June

    2013-08-20

    Lineage 2 West Nile Virus (WNV) is endemic to southern Africa and Madagascar, and has recently been associated with encephalitis outbreaks in humans and horses in South Africa, central Europe, Italy and Greece. Commercial vaccines have mostly been evaluated against WNV lineage 1 strains and their efficacy against lineage 2 strains rarely reported. To evaluate protection of Duvaxyn WNV vaccine against lineage 2 strains associated with encephalitis in South Africa, mice were vaccinated twice intramuscularly three weeks apart, and challenged four weeks later with highly neuroinvasive lineage 1 strain NY385/99 or lineage 2 strain SPU93/01. Neutralising antibody titres were measured at the time of challenge and three weeks later. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were conducted on brains of mice that succumbed during the trial, on controls and on vaccinated mice that survived. Serum neutralising antibodies in vaccinated mice were detected but low three weeks after primovaccination. Three weeks post-challenge, vaccinated mice had significantly higher serum neutralising antibody titres against both lineages than unvaccinated controls. After challenge, all vaccinated mice remained healthy but all unvaccinated mice demonstrated severe neurological signs with 75% mortality rate. WNV was not detected in brains of vaccinated mice whereas virus replicated in most unvaccinated mice challenged with either lineage. Gross and microscopic lesions were found only in unvaccinated mice challenged with both lineages. Duvaxyn WNV vaccine provided complete protection against challenge with lineage 2 WNV and stimulated significant cross protective neutralising antibodies in mice against lineage 2. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Three cases of paralytic poliomyelitis associated with type 3 vaccine poliovirus strains in Bulgaria.

    PubMed

    Korsun, Neli; Kojouharova, Mira; Vladimirova, Nadezhda; Fiore, Lucia; Litvinenko, Ivan; Buttinelli, Gabriele; Fiore, Stefano; Voynova-Georgieva, Violeta; Mladenova, Zornitsa; Georgieva, Daniela

    2009-09-01

    Oral poliovirus vaccine (OPV) can cause, in extremely rare cases vaccine-associated paralytic poliomyelitis in recipients, or contacts of vaccinees. Three cases of vaccine-associated paralytic poliomyelitis (two contacts and one recipient) occurred in the Bourgas region of Bulgaria in the spring of 2006. The first two cases, notified as acute flaccid paralysis, were 55 days old unvaccinated twin brothers, having been in contact with vaccinees. The third case concerned a 4-month-old infant who had received the first OPV dose 37 days prior to the onset of illness. Complete clinical, epidemiological, virological, serological and molecular investigations of the children with paralysis and their contacts were undertaken. In all the three cases type 3 polioviruses were isolated from fecal samples and characterized as Sabin-like poliovirus strains. Type 3 polioviruses isolated from the twin brothers demonstrated by sequence analysis U-to-C back mutation at nt 472 of the 5' UTR, known to correlate with neurovirulence, and mutation in the VP1 region. Type 3 poliovirus isolated from the third child demonstrated in the 3D sequenced region a recombination with Sabin type 1 poliovirus. In the latter region, three silent mutations and one, resulting in amino acid substitution, were also observed. The clinical, epidemiological and virological data and the neurological sequelae observed 60 days following the onset of paralysis, confirmed the diagnosis of vaccine-associated paralytic poliomyelitis in all the three patients.

  8. Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008–2013

    PubMed Central

    Bowen, Michael D.; Mijatovic-Rustempasic, Slavica; Esona, Mathew D.; Teel, Elizabeth N.; Gautam, Rashi; Sturgeon, Michele; Azimi, Parvin H.; Baker, Carol J.; Bernstein, David I.; Boom, Julie A.; Chappell, James; Donauer, Stephanie; Edwards, Kathryn M.; Englund, Janet A.; Halasa, Natasha B.; Harrison, Christopher J.; Johnston, Samantha H.; Klein, Eileen J.; McNeal, Monica M.; Moffatt, Mary E.; Rench, Marcia A.; Sahni, Leila C.; Selvarangan, Rangaraj; Staat, Mary A.; Szilagyi, Peter G.; Weinberg, Geoffrey A.; Wikswo, Mary E.; Parashar, Umesh D.; Payne, Daniel C.

    2016-01-01

    Background Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at 3–7 geographically diverse sites in the United States since 2006. Methods Over 6 consecutive years, from 2008 to 2013, 1523 samples from NVSN sites that were tested positive by a Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention for genotyping. Results In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network, with a 46%–84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype, with a 70% prevalence, and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq; Rotarix) strains were detected in 0.6%–3.4% of genotyped samples each season. Uncommon and unusual strains (eg, G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], and G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. Conclusions Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure. PMID:27302190

  9. Establishment of reverse genetics system for infectious bronchitis virus attenuated vaccine strain H120.

    PubMed

    Zhou, Ying Shun; Zhang, Yi; Wang, Hong Ning; Fan, Wen Qiao; Yang, Xin; Zhang, An Yun; Zeng, Fan Ya; Zhang, Zhi Kun; Cao, Hai Peng; Zeng, Cheng

    2013-02-22

    Infectious bronchitis virus (IBV) strain H120 was successfully rescued as infectious clone by reverse genetics. Thirteen 1.5-2.8 kb fragments contiguously spanning the virus genome were amplified and cloned into pMD19-T. Transcription grade complete length cDNA was acquired by a modified "No See'm" ligation strategy, which employed restriction enzyme Bsa I and BsmB I and ligated more than two fragments in one T4 ligase reaction. The full-length genomic cDNA was transcribed and its transcript was transfected by electroporation into BHK-21 together with the transcript of nucleocapsid gene. At 48 h post transfection, the medium to culture the transfected BHK-21 cells was harvested and inoculated into 10-days old SPF embryonated chicken eggs (ECE) to replicate the rescued virus. After passage of the virus in ECE five times, the rescued H120 virus (R-H120) was successfully recovered. R-H120 was subsequently identified to possess the introduced silent mutation site in its genome. Some biological characteristics of R-H120 such as growth curve, EID50 and HA titers, were tested and all of them were very similar to its parent strain H120. In addition, both R-H120 and H120 induced a comparable titer of HA inhibition (HI) antibody in immunized chickens and also provided up to 85% of immune protection to the chickens that were challenged with Mass41 IBV strain. The present study demonstrated that construction of infectious clone from IBV vaccine strain H120 is possible and IBV-H120 can be use as a vaccine vector for the development of novel vaccines through molecular recombination and the modified reverse genetics approach.

  10. Comparative Respiratory Pathogenicity and Dynamic Tissue Distribution of Chinese Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and its Attenuated Strain in Piglets.

    PubMed

    Liu, C; Zhang, W; Gong, W; Zhang, D; She, R; Xu, B; Ning, Y

    2015-07-01

    The outbreak of highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS) in 2006 devastated the Chinese swine industry. HP-PRRS virus is still the predominant strain in mainland China, rather than the classical PRRSV strain, and the attenuated live vaccine remains the preferred choice for protecting piglets against HP-PRRSV infection. To fully evaluate the safety of strain GDr180, the 180th attenuated virus of the HP-PRRSV strain GD, we used clinicopathological, microscopical, ultrastructural, serological and molecular biological methods to assess the different clinical manifestations and respiratory characteristics of piglets inoculated with HP-PRRSV strain GD or strain GDr180. The 5-week-old piglets inoculated with strain GD displayed marked clinical signs, including fever, anorexia, dyspnoea and tachypnoea. Significant interstitial pneumonia was present, characterized by thickened alveolar septa infiltrated with mononuclear cells and cell debris. However, the piglets inoculated with strain GDr180 and the negative control piglets showed neither clinical signs nor microscopical or ultrastructural lesions. Ultrastructural observation of the piglets' tracheas and examination of the dynamic tissue distributions of PRRSV strain GD and attenuated strain GDr180, by immunohistochemistry and fluorescence quantitative reverse transcription-polymerase chain reaction, confirmed significant differences in their pathogenicity and distribution in the respiratory systems of piglets. The differences in pathogenicity are attributable to the different severity of the pathological changes in the pigs inoculated with the two strains. Thus, the HP-PRRSV GDr180 strain is practically harmless to the respiratory systems of piglets and may be a safe candidate for inducing immunity against HP-PRRS.

  11. Models derived from in vitro analyses of spleen, liver, and lung leukocyte functions predict vaccine efficacy against the Francisella tularensis Live Vaccine Strain (LVS).

    PubMed

    De Pascalis, Roberto; Chou, Alicia Y; Ryden, Patrik; Kennett, Nikki J; Sjöstedt, Anders; Elkins, Karen L

    2014-04-08

    Currently, there are no licensed vaccines and no correlates of protection against Francisella tularensis, which causes tularemia. We recently demonstrated that measuring in vitro control of intramacrophage bacterial growth by murine F. tularensis-immune splenocytes, as well as transcriptional analyses, discriminated Francisella vaccines of different efficacies. Further, we identified potential correlates of protection against systemic challenge. Here, we extended this approach by studying leukocytes derived from lungs and livers of mice immunized by parenteral and respiratory routes with F. tularensis vaccines. Liver and lung leukocytes derived from intradermally and intranasally vaccinated mice controlled in vitro Francisella Live Vaccine Strain (LVS) intramacrophage replication in patterns similar to those of splenocytes. Gene expression analyses of potential correlates also revealed similar patterns in liver cells and splenocytes. In some cases (e.g., tumor necrosis factor alpha [TNF-α], interleukin 22 [IL-22], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), liver cells exhibited even higher relative gene expression, whereas fewer genes exhibited differential expression in lung cells. In contrast with their strong ability to control LVS replication, splenocytes from intranasally vaccinated mice expressed few genes with a hierarchy of expression similar to that of splenocytes from intradermally vaccinated mice. Thus, the relative levels of gene expression vary between cell types from different organs and by vaccination route. Most importantly, because studies comparing cell sources and routes of vaccination supported the predictive validity of this coculture and gene quantification approach, we combined in vitro LVS replication with gene expression data to develop analytical models that discriminated between vaccine groups and successfully predicted the degree of vaccine efficacy. Thus, this strategy remains a promising means of identifying and

  12. Comparative genomic analysis of Brucella melitensis vaccine strain M5 provides insights into virulence attenuation.

    PubMed

    Jiang, Hai; Du, Pengcheng; Zhang, Wen; Wang, Heng; Zhao, Hongyan; Piao, Dongri; Tian, Guozhong; Chen, Chen; Cui, Buyun

    2013-01-01

    The Brucella melitensis vaccine strain M5 is widely used to prevent and control brucellosis in animals. In this study, we determined the whole-genome sequence of M5, and conducted a comprehensive comparative analysis against the whole-genome sequence of the virulent strain 16 M and other reference strains. This analysis revealed 11 regions of deletion (RDs) and 2 regions of insertion (RIs) within the M5 genome. Among these regions, the sequences encompassed in 5 RDs and 1 RI showed consistent variation, with a large deletion between the M5 and the 16 M genomes. RD4 and RD5 showed the large diversity among all Brucella genomes, both in RD length and RD copy number. Thus, RD4 and RD5 are potential sites for typing different Brucella strains. Other RD and RI regions exhibited multiple single nucleotide polymorphisms (SNPs). In addition, a genome fragment with a 56 kb rearrangement was determined to be consistent with previous studies. Comparative genomic analysis indicated that genomic island inversion in Brucella was widely present. With the genetic pattern common among all strains analyzed, these 2 RDs, 1 RI, and one inversion region are potential sites for detection of genomic differences. Several SNPs of important virulence-related genes (motB, dhbC, sfuB, dsbAB, aidA, aroC, and lysR) were also detected, and may be used to determine the mechanism of virulence attenuation. Collectively, this study reveals that comparative analysis between wild-type and vaccine strains can provide resources for the study of virulence and microevolution of Brucella.

  13. Comparative Genomic Analysis of Brucella melitensis Vaccine Strain M5 Provides Insights into Virulence Attenuation

    PubMed Central

    Zhang, Wen; Wang, Heng; Zhao, Hongyan; Piao, Dongri; Tian, Guozhong; Chen, Chen; Cui, Buyun

    2013-01-01

    The Brucella melitensis vaccine strain M5 is widely used to prevent and control brucellosis in animals. In this study, we determined the whole-genome sequence of M5, and conducted a comprehensive comparative analysis against the whole-genome sequence of the virulent strain 16 M and other reference strains. This analysis revealed 11 regions of deletion (RDs) and 2 regions of insertion (RIs) within the M5 genome. Among these regions, the sequences encompassed in 5 RDs and 1 RI showed consistent variation, with a large deletion between the M5 and the 16 M genomes. RD4 and RD5 showed the large diversity among all Brucella genomes, both in RD length and RD copy number. Thus, RD4 and RD5 are potential sites for typing different Brucella strains. Other RD and RI regions exhibited multiple single nucleotide polymorphisms (SNPs). In addition, a genome fragment with a 56 kb rearrangement was determined to be consistent with previous studies. Comparative genomic analysis indicated that genomic island inversion in Brucella was widely present. With the genetic pattern common among all strains analyzed, these 2 RDs, 1 RI, and one inversion region are potential sites for detection of genomic differences. Several SNPs of important virulence-related genes (motB, dhbC, sfuB, dsbAB, aidA, aroC, and lysR) were also detected, and may be used to determine the mechanism of virulence attenuation. Collectively, this study reveals that comparative analysis between wild-type and vaccine strains can provide resources for the study of virulence and microevolution of Brucella. PMID:23967122

  14. A reassortment-incompetent live attenuated influenza virus vaccine for use in protection against pandemic virus strains

    USDA-ARS?s Scientific Manuscript database

    Although live-attenuated influenza vaccines (LAIV) are safe for use in protection against seasonal influenza strains, concerns over their potential to reassort with wild-type virus strains have been voiced. LAIVs have been demonstrated to induce enhanced mucosal and cell-mediated immunity over inac...

  15. Genomic sequence analysis of the United States infectious laryngotracheitis vaccine strains chicken embryo origin (CEO) and tissue culture origin (TCO)

    USDA-ARS?s Scientific Manuscript database

    The genomic sequences of low and high passages of U.S. infectious laryngotracheitis (ILT) vaccine strains chicken embryo origin (CEO) and tissue culture origin (TCO) these strains were determined using hybrid next generation sequencing in order to define relevant genomic changes associated with att...

  16. Development of a Recombinant Newcastle Disease Virus VG/GA Strain Infectious Clone as an Enterotropic Vaccine Vector

    USDA-ARS?s Scientific Manuscript database

    The Villegas-Glisson/University of Georgia (VG/GA) vaccine strain of Newcastle disease virus (NDV) is commonly used worldwide to prevent Newcastle disease. The VG/GA strain is thought to preferentially replicate in intestinal tract of chickens and induce local mucosal immunoresponse. In the presen...

  17. Vaccination with Vesicular Stomatitis Virus-Vectored Chimeric Hemagglutinins Protects Mice against Divergent Influenza Virus Challenge Strains.

    PubMed

    Ryder, Alex B; Nachbagauer, Raffael; Buonocore, Linda; Palese, Peter; Krammer, Florian; Rose, John K

    2015-12-16

    Seasonal influenza virus infections continue to cause significant disease each year, and there is a constant threat of the emergence of reassortant influenza strains causing a new pandemic. Available influenza vaccines are variably effective each season, are of limited scope at protecting against viruses that have undergone significant antigenic drift, and offer low protection against newly emergent pandemic strains. "Universal" influenza vaccine strategies that focus on the development of humoral immunity directed against the stalk domains of the viral hemagglutinin (HA) show promise for protecting against diverse influenza viruses. Here, we describe such a strategy that utilizes vesicular stomatitis virus (VSV) as a vector for chimeric hemagglutinin (cHA) antigens. This vaccination strategy is effective at generating HA stalk-specific, broadly cross-reactive serum antibodies by both intramuscular and intranasal routes of vaccination. We show that prime-boost vaccination strategies provide protection against both lethal homologous and heterosubtypic influenza challenge and that protection is significantly improved with intranasal vaccine administration. Additionally, we show that vaccination with VSV-cHAs generates greater stalk-specific and cross-reactive serum antibodies than does vaccination with VSV-vectored full-length HAs, confirming that cHA-based vaccination strategies are superior at generating stalk-specific humoral immunity. VSV-vectored influenza vaccines that express chimeric hemagglutinin antigens offer a novel means for protecting against widely diverging influenza viruses. Universal influenza vaccination strategies should be capable of protecting against a wide array of influenza viruses, and we have developed such an approach utilizing a single viral vector system. The potent antibody responses that these vaccines generate are shown to protect mice against lethal influenza challenges with highly divergent viruses. Notably, intranasal vaccination

  18. Construction and Characterization of an Attenuated Purine Auxotroph in a Francisella tularensis Live Vaccine Strain

    PubMed Central

    Pechous, Roger; Celli, Jean; Penoske, Renee; Hayes, Stanley F.; Frank, Dara W.; Zahrt, Thomas C.

    2006-01-01

    Francisella tularensis is a facultative intracellular pathogen and is the etiological agent of tularemia. It is capable of escaping from the phagosome, replicating to high numbers in the cytosol, and inducing apoptosis in macrophages of a variety of hosts. F. tularensis has received significant attention recently due to its potential use as a bioweapon. Currently, there is no licensed vaccine against F. tularensis, although a partially protective live vaccine strain (LVS) that is attenuated in humans but remains fully virulent for mice was previously developed. An F. tularensis LVS mutant deleted in the purMCD purine biosynthetic locus was constructed and partially characterized by using an allelic exchange strategy. The F. tularensis LVS ΔpurMCD mutant was auxotrophic for purines when grown in defined medium and exhibited significant attenuation in virulence when assayed in murine macrophages in vitro or in BALB/c mice. Growth and virulence defects were complemented by the addition of the purine precursor hypoxanthine or by introduction of purMCDN in trans. The F. tularensis LVS ΔpurMCD mutant escaped from the phagosome but failed to replicate in the cytosol or induce apoptotic and cytopathic responses in infected cells. Importantly, mice vaccinated with a low dose of the F. tularensis LVS ΔpurMCD mutant were fully protected against subsequent lethal challenge with the LVS parental strain. Collectively, these results suggest that F. tularensis mutants deleted in the purMCD biosynthetic locus exhibit characteristics that may warrant further investigation of their use as potential live vaccine candidates. PMID:16861631

  19. Effects of vaccination and population structure on influenza epidemic spread in the presence of two circulating strains.

    PubMed

    Alexander, Murray E; Kobes, Randy

    2011-02-25

    Human influenza is characterized by seasonal epidemics, caused by rapid viral adaptation to population immunity. Vaccination against influenza must be updated annually, following surveillance of newly appearing viral strains. During an influenza season, several strains may be co-circulating, which will influence their individual evolution; furthermore, selective forces acting on the strains will be mediated by the transmission dynamics in the population. Clearly, viral evolution and public health policy are strongly interconnected. Understanding population-level dynamics of coexisting viral influenza infections, would be of great benefit in designing vaccination strategies. We use a Markov network to extend a previous homogeneous model of two co-circulating influenza viral strains by including vaccination (either prior to or during an outbreak), age structure, and heterogeneity of the contact network. We explore the effects of changes in vaccination rate, cross-immunity, and delay in appearance of the second strain, on the size and timing of infection peaks, attack rates, and disease-induced mortality rate; and compare the outcomes of the network and corresponding homogeneous models. Pre-vaccination is more effective than vaccination during an outbreak, resulting in lower attack rates for the first strain but higher attack rates for the second strain, until a "threshold" vaccination level of ~30-40% is reached, after which attack rates due to both strains sharply dropped. A small increase in mortality was found for increasing pre-vaccination coverage below about 40%, due to increasing numbers of strain 2 infections. The amount of cross-immunity present determines whether a second wave of infection will occur. Some significant differences were found between the homogeneous and network models, including timing and height of peak infection(s). Contact and age structure significantly influence the propagation of disease in the population. The present model explores

  20. Generation of a live rabies vaccine strain attenuated by multiple mutations and evaluation of its safety and efficacy.

    PubMed

    Nakagawa, Keisuke; Ito, Naoto; Masatani, Tatsunori; Abe, Masako; Yamaoka, Satoko; Ito, Yuki; Okadera, Kota; Sugiyama, Makoto

    2012-05-21

    An amino acid substitution at position 333 in rabies virus G protein is known to determine the pathogenicity: strains with Arg or Lys at that position kill adult mice after intracerebral inoculation, whereas strains with other amino acids cause non-lethal infection. Based on those findings, attenuated rabies virus strains have been established and used for oral vaccines mainly for wild animals. However, considering the possibility of back-mutation to the virulent phenotype, a strain that is attenuated by multiple mutations not only in the G protein but also in other viral proteins would be more appropriate as a safe live vaccine. We previously demonstrated that the fixed rabies virus Ni-CE strain, which causes only transient body weight loss in adult mice after intracerebral inoculation, is mainly attenuated by mutations in the N, P and M proteins, while this strain has virulent-type Arg at position 333 in the G protein. In this study, to obtain a live vaccine strain that is attenuated by multiple mutations, we generated Ni-CE mutant, Ni-CE(G333Glu) strain, which has an Arg-to-Glu mutation at position 333 in the G protein, and examined its pathogenicity and immunogenicity. We found that, in contrast to Ni-CE strain, Ni-CE(G333Glu) strain did not cause transient body weight loss in adult mice after intracerebral inoculation. The attenuated phenotype of Ni-CE(G333Glu) strain did not change even after 10 serial intracerebral passages in suckling mice. We also demonstrated that inoculation of Ni-CE(G333Glu) strain induced virus-neutralizing antibody in immunized mice and protected the mice from lethal challenge. These results indicate that Ni-CE(G333Glu) strain is a promising candidate for development of a live rabies vaccine with a high safety level.

  1. Protective efficacy of multivalent replication-abortive vaccine strains in horses against African horse sickness virus challenge.

    PubMed

    Lulla, Valeria; Losada, Andres; Lecollinet, Sylvie; Kerviel, Adeline; Lilin, Thomas; Sailleau, Corinne; Beck, Cecile; Zientara, Stephan; Roy, Polly

    2017-07-24

    African horse sickness virus (AHSV) is an orbivirus, a member of the Reoviridae family. Nine different serotypes have been described so far. AHSV is vectored by Culicoides spp. to equids, causing high mortality, particularly in horses, with considerable economic impacts. For development of a safe attenuated vaccine, we previously established an efficient reverse genetics (RG) system to generate Entry Competent Replication-Abortive (ECRA) virus strains, for all nine serotypes and demonstrated the vaccine potential of these strains in type I interferon receptor (IFNAR)-knockout mice. Here, we evaluated the protective efficacies of these ECRA viruses in AHSV natural hosts. One monoserotype (ECRA.A4) vaccine and one multivalent cocktail (ECRA.A1/4/6/8) vaccine were tested in ponies and subsequently challenged with a virulent AHSV4. In contrast to control animals, all vaccinated ponies were protected and did not develop severe clinical symptoms of AHS. Furthermore, the multivalent cocktail vaccinated ponies produced neutralizing antibodies against all serotypes present in the cocktail, and a foal born during the trial was healthy and had no viremia. These results validate the suitability of these ECRA strains as a new generation of vaccines for AHSV. Copyright © 2017. Published by Elsevier Ltd.

  2. Evaluation results of the 700 deg C Chinese strain gauges. [for gas turbine engine

    NASA Technical Reports Server (NTRS)

    Hobart, H. F.

    1985-01-01

    Gauges fabricated from specially developed Fe-Cr-Al-V-Ti-Y alloy wire in the Republic of China were evaluated for use in static strain measurement of hot gas turbine engines. Gauge factor variation with temperature, apparent strain, and drift were included. Results of gauge factor versus temperature tests show gauge factor decreasing with increasing temperature. The average slope is -3-1/2 percent/100 K, with an uncertainty band of + or - 8 percent. Values of room temperature gauge factor for the Chinese and Kanthal A-1 gauges averaged 2.73 and 2.12, respectively. The room temperature gauge factor of the Chinese gauges was specified to be 2.62. The apparent strain data for both the Chinese alloy and Kanthal A-1 showed large cycle to cycle nonrepeatability. All apparent strain curves had a similar S-shape, first going negative and then rising to positive value with increasing temperatures. The mean curve for the Chinese gauges between room temperature and 100 K had a total apparent strain of 1500 microstrain. The equivalent value for Kanthal A-1 was about 9000 microstrain. Drift tests at 950 K for 50 hr show an average drift rate of about -9 microstrain/hr. Short-term (1 hr) rates are higher, averaging about -40 microstrain for the first hour. In the temperature range 700 to 870 K, however, short-term drift rates can be as high as 1700 microstrain for the first hour. Therefore, static strain measurements in this temperature range should be avoided.

  3. Influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses.

    PubMed

    Russell, Colin A; Jones, Terry C; Barr, Ian G; Cox, Nancy J; Garten, Rebecca J; Gregory, Vicky; Gust, Ian D; Hampson, Alan W; Hay, Alan J; Hurt, Aeron C; de Jong, Jan C; Kelso, Anne; Klimov, Alexander I; Kageyama, Tsutomu; Komadina, Naomi; Lapedes, Alan S; Lin, Yi P; Mosterin, Ana; Obuchi, Masatsugu; Odagiri, Takato; Osterhaus, Albert D M E; Rimmelzwaan, Guus F; Shaw, Michael W; Skepner, Eugene; Stohr, Klaus; Tashiro, Masato; Fouchier, Ron A M; Smith, Derek J

    2008-09-12

    Annual influenza epidemics in humans affect 5-15% of the population, causing an estimated half million deaths worldwide per year [Stohr K. Influenza-WHO cares. Lancet Infectious Diseases 2002;2(9):517]. The virus can infect this proportion of people year after year because the virus has an extensive capacity to evolve and thus evade the immune response. For example, since the influenza A(H3N2) subtype entered the human population in 1968 the A(H3N2) component of the influenza vaccine has had to be updated almost 30 times to track the evolution of the viruses and remain effective. The World Health Organization Global Influenza Surveillance Network (WHO GISN) tracks and analyzes the evolution and epidemiology of influenza viruses for the primary purpose of vaccine strain selection and to improve the strain selection process through studies aimed at better understanding virus evolution and epidemiology. Here we give an overview of the strain selection process and outline recent investigations into the global migration of seasonal influenza viruses.

  4. Effect of a monovalent vaccine against Leptospira borgpetersenii serovar Hardjo strain hardjobovis on fertility in Holstein dairy cattle.

    PubMed

    Plunkett, Amanda H; Graham, Thomas W; Famula, Thomas R; Oberbauer, Anita M

    2013-06-01

    To determine whether vaccination with a monovalent vaccine against Leptospira borgpetersenii serovar Hardjo strain hardjobovis would improve reproductive efficiency in Holstein cattle in a commercial dairy setting. Randomized controlled trial. 1,894 Holstein cows and heifers from a Central California dairy. Cattle were assigned to undergo SC administration of a monovalent vaccine against Leptospira borgpetersenii serovar Hardjo strain hardjobovis (n = 986) or a placebo (lactated Ringer's solution; 908). At the end of their lactation period, cows received 2 doses of the vaccine or placebo, 28 to 35 days apart, with the initial dose administered in conjunction with oxytetracycline. Heifers received the same treatments, with the second dose administered at least 2 weeks before their entrance into the heifer breeding pen. Urine and blood samples were collected from randomly selected cattle immediately before and 1 year after the trial began and submitted for fluorescent antibody and microscopic agglutination testing to identify any infecting Leptospira serovar. The initial herd prevalence of active infection with strain hardjobovis was 13% (6/46 tested cattle), followed by 15% (6/40) 1 year after the trial began. The odds of heifers conceiving over the period at risk for conception, regardless of vaccination, was approximately 2.8 times as high as for primiparous and pluriparous cows. Survival analysis of days from parturition to conception revealed that the vaccine protocol had no effect on the probability of conception between the vaccinated and control groups. The vaccine protocol had no impact on pregnancy loss. The evaluated vaccination protocol against Leptospira strain hardjobovis was not effective in improving reproductive efficiency in commercial Holstein dairy cows or in decreasing urine shedding of leptospires.

  5. Development of inactivated poliovirus vaccine from Sabin strains: A progress report.

    PubMed

    Okayasu, Hiromasa; Sein, Carolyn; Hamidi, Ahd; Bakker, Wilfried A M; Sutter, Roland W

    2016-11-01

    The Global Polio Eradication Initiative (GPEI) has seen significant progress since it began in 1988, largely due to the worldwide use of oral poliovirus vaccine (OPV). In order to achieve polio eradication the global cessation of OPV is necessary because OPV contains live attenuated poliovirus, which in rare circumstances could re-gain wild poliovirus (WPV) characteristics with potential to establish transmission. The GPEI endgame strategy for the period 2013-2018 recommends the globally synchronised sequential cessation of the Sabin strains contained in the OPV, starting with type 2 Sabin. The withdrawal of Sabin type 2 took place in April 2016, with the introduction of at least one dose of inactivated poliovirus vaccine (IPV) as a risk mitigation strategy. The introduction of IPV into 126 countries since 2013 has required a rapid scale-up of IPV production by the two manufacturers supplying the global public sector market. This scale-up has been fraught with challenges, resulting in reductions of 40-50% of initial supply commitments. Consequently, 22 countries will not be supplied until 2018, and another 23 countries will experience serious stock-outs. In the last decade repeated calls-for-action were made to the global community to invigorate their vision and investment in developing "new poliovirus vaccines" including the development of IPV from less-virulent strains, such as Sabin-IPV (S-IPV). The conventional Salk-IPV production is limited to high-income industrialized-country manufacturers due to the containment requirements (i.e., high sanitation, low force-of-poliovirus-infection, and high population immunity). The use of Sabin strains in the production of S-IPV carries a lower biosafety risk, and was determined to be suitable for production in developing countries, expanding the manufacturing base and making IPV more affordable and accessible in the long term. Significant progress in the S-IPV has been made since 2006. S-IPV is now licensed as S-IPV in

  6. Safety and efficacy of reduced doses of Brucella melitensis strain Rev. 1 vaccine in pregnant Iranian fat-tailed ewes.

    PubMed

    Ebrahimi, Mohammad; Nejad, Ramin Bagheri; Alamian, Saeed; Mokhberalsafa, Ladan; Abedini, Fatemeh; Ghaderi, Rainak; Jalali, Hamid Reza

    2012-01-01

    Brucellosis is one of the most important zoonotic diseases and is a significant cause of abortion in animals. Brucella melitensis strain Rev. 1 is recommended as the most effective vaccine for small ruminants but the application of full doses in adult animals is restricted. This study was conducted to determine a proper reduced dose of vaccine which confers protection but which is not abortifacient in Iranian fat-tailed sheep. A total of 51 non-vaccinated pregnant ewes were divided into three main groups and several subgroups. Ewes in different groups were vaccinated at different stages of pregnancy and various subgroups were subcutaneously immunised with different quantities of the micro-organism (7.5 × 10(6), 10(6), 5 × 10(5)). Ewes again became pregnant a year later and were challenged with the wild-type strain to evaluate the protection conferred. Results revealed that the proportion of vaccination-induced abortions was significantly higher in ewes immunised with 7.5 × 10(6) Rev. 1 organisms than in those which received 10(6) or 5 × 10(5) bacteria. While 80% of non-vaccinated ewes aborted after challenge, none of the vaccinated ewes aborted post-challenge. This study indicated that a reduced dose of Rev. 1 vaccine containing 10(6) or 5 × 10(5) live cells could be safely used to induce protection in Iranian fat-tailed sheep at various stages of pregnancy.

  7. Increased efficacy of inactivated vaccine candidates prepared with Salmonella enterica serovar Typhimurium strains of predominant genotypes in ducks.

    PubMed

    Youn, S Y; Kwon, Y K; Song, C S; Lee, H J; Jeong, O M; Choi, B K; Jung, S C; Kang, M S

    2016-08-01

    Salmonella enterica serovar Typhimurium has been a major causative agent of food-borne human disease, mainly due to consumption of contaminated food animal products. In particular, ducks serve as a reservoir of serovar Typhimurium, and are one of the common sources of human infection. To prevent infection of ducks, and therefore minimize human infection, it is critical to control the persistent epidemic strains in ducks. Here, we analyzed the genetic diversity and virulence of serovar Typhimurium isolates from ducks in Korea to identify the predominant strains that might be used as efficient vaccine candidates for ducks. Among the isolates, 2 representative isolates (ST26 and ST76) of predominant genotypes were selected as vaccine strains on the basis of genotypic analysis by pulsed-field gel electrophoresis and DNA microarrays. Two-week-old ducks were then injected intramuscularly with inactivated vaccine candidates prepared using ST26 or ST76 (10(8) cfu/0.5 mL/duck or 10(9) cfu/0.5 mL/duck), and oral challenge with a highly virulent serovar Typhimurium strain (10(9) cfu/0.5 mL/duck) was carried out 2 wk later. Shedding of the challenge strain was significantly decreased in group 2 after vaccination. The antibody levels by enzyme-linked immunosorbent assay in all vaccinated groups were enhanced significantly (P < 0.05) compared to the unvaccinated control group. Overall, vaccination with ST26 or ST76 reduced bacterial shedding and colonization in internal organs, and induced elevated antibody response. In particular, serovar Typhimurium ST26 (10(8) cfu/0.5 mL/duck) was the most effective vaccine candidate, which can provide efficient protection against serovar Typhimurium in ducks with higher effectiveness compared to a commercial vaccine currently used worldwide. © 2016 Poultry Science Association Inc.

  8. Identification of an IS711 Element Interrupting the wboA Gene of Brucella abortus Vaccine Strain RB51 and a PCR Assay To Distinguish Strain RB51 from Other Brucella Species and Strains

    PubMed Central

    Vemulapalli, Ramesh; McQuiston, John R.; Schurig, Gerhardt G.; Sriranganathan, Nammalwar; Halling, Shirley M.; Boyle, Stephen M.

    1999-01-01

    Brucella abortus vaccine strain RB51 is a natural stable attenuated rough mutant derived from the virulent strain 2308. The genetic mutations that are responsible for the roughness and the attenuation of strain RB51 have not been identified until now. Also, except for an assay based on pulsed-field gel electrophoresis, no other simple method to differentiate strain RB51 from its parent strain 2308 is available. In the present study, we demonstrate that the wboA gene encoding a glycosyltransferase, an enzyme essential for the synthesis of O antigen, is disrupted by an IS711 element in B. abortus vaccine strain RB51. Exploiting this feature, we developed a PCR assay that distinguishes strain RB51 from all other Brucella species and strains tested. PMID:10473532

  9. Protection from lethal herpes simplex virus type 1 infection by vaccination with a UL41-deficient recombinant strain.

    PubMed

    Koshizuka, Tetsuo; Ishioka, Ken; Kobayashi, Takahiro; Ikuta, Kazufumi; Suzutani, Tatsuo

    2016-06-08

    The UL41 gene of herpes simplex virus type 1 (HSV-1) encodes a virion host shut off protein which is involved in immune evasion. The growth and virulence of HSV-1 is markedly reduced by the deletion of UL41. In this report, the UL41-deleted recombinant HSV-1 strain VR∆41 was evaluated as a prophylactic live attenuated vaccine against lethal HSV-1 infection in a mouse model. Intraperitoneal (i.p.) inoculation with the VR∆41 strain clearly inhibited lethal wild-type HSV-1 (VR-3 strain) infection after both i.p. and intracerebral (i.c.) inoculations. Vaccination with the VR∆41 strain was safer than VR-3 vaccination and was able to protect against a wild-type challenge to the same degree as VR-3 vaccination. In contrast, i.p. inoculation with ultraviolet-irradiated VR-3 induced resistance against i.p. infection, but not against i.c. Although replication of the VR∆41 strain in mice was greatly reduced compared to that of the VR-3 strain, VR∆41 strain maintained the ability to spread to the central nervous system (CNS) from a peripheral inoculation site. These results indicated that the VR∆41 strain evoked a potent immune reaction through viral protein expression within CNS without the induction of lethal encephalitis. The entry of antigens into the CNS was essential for the establishment of protective immunity against the lethal HSV encephalitis. We concluded that only a live attenuated vaccine is able to afford a prophylactic effect against CNS infection with HSV. In order to fulfill this requirement, UL41-deleted viruses provide a strong candidate for use as a recombinant live vaccine.

  10. A comparative study between excretory/secretory and autoclaved vaccines against RH strain of Toxoplasma gondii in murine models.

    PubMed

    Ezz Eldin, Hayam Mohamed; Kamel, Hanan Hussein; Badawy, Abeer Fathy; Shash, Lobna Sadek

    2015-09-01

    Toxoplasma gondii is an obligate intracellular protozoan that has a major importance in public health, in addition to veterinary medicine. Therefore, the development of an effective vaccine for controlling toxoplasmosis is an important goal. Excretory/secretory antigens (ESA), were previously identified as potential vaccine candidates, proved to play important roles in the pathogenesis and immune escape of the parasite. In addition, autoclaved Toxoplasma vaccine (ATV) is a special type of killed vaccine, recently characterized. The aim of the present work was, to compare between excretory/secretory and ATV against RH strain of T. gondii in mice based on; parasitological and histopathological levels. Tachyzoites were harvested from peritoneal exudates of infected mice and were used for challenge infection and vaccine preparation. BCG was used as an adjuvant. Mice were allocated equally into five groups; they were vaccinated intradermally over the sternum. The results of this study showed that the survival time after challenge, extended up to 16 days in ESA vaccinated group and up to 15 days in autoclaved Toxoplasma vaccinated group. ESA vaccinated group exhibited a profound decrease in parasite load following parasite challenge with a higher percentage of reduction in parasite count in all examined organs than the autoclaved Toxoplasma vaccinated group. The histopathological picture of the liver in both immunized groups, revealed marked reduction in the pathological changes observed as compared to controls, especially in ESA vaccinated group. It was concluded that vaccination with ESA showed more promising results versus ATV, as demonstrated by the survival rate of vaccinated mice, tachyzoites count and histopathological examination.

  11. The effect of bacille Calmette-Guérin vaccine strain and route of administration on induced immune responses in vaccinated infants.

    PubMed

    Davids, Virginia; Hanekom, Willem A; Mansoor, Nazma; Gamieldien, Hoyam; Gelderbloem, Sebastian J; Hawkridge, Anthony; Hussey, Gregory D; Hughes, E Jane; Soler, Jorge; Murray, Rose Ann; Ress, Stanley R; Kaplan, Gilla

    2006-02-15

    Vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) has variable efficacy in preventing tuberculosis. Both BCG strain and route of administration have been implicated in determining efficacy; however, these variables are not considered in current clinical recommendations for vaccine choice. We evaluated antigen-specific immunity after percutaneous or intradermal administration of Japanese BCG or intradermal administration of Danish BCG. Ten weeks after vaccination of neonates, percutaneous Japanese BCG had induced significantly higher frequencies of BCG-specific interferon- gamma -producing CD4(+) and CD8(+) T cells in BCG-stimulated whole blood than did intradermal Danish BCG. Similarly, percutaneous vaccination with Japanese BCG resulted in significantly greater secretion of the T helper 1-type cytokines interferon- gamma, tumor necrosis factor- alpha , and interleukin-2; significantly lower secretion of the T helper 2-type cytokine interleukin-4; and greater CD4(+) and CD8(+) T cell proliferation. Thus, BCG strain and route of neonatal vaccination confer different levels of immune activation, which may affect the efficacy of the vaccine.

  12. Prior infection with influenza virus but not vaccination leaves a long-term immunological imprint that intensifies the protective efficacy of antigenically drifted vaccine strains.

    PubMed

    Kim, Jin Hyang; Liepkalns, Justine; Reber, Adrian J; Lu, Xiuhua; Music, Nedzad; Jacob, Joshy; Sambhara, Suryaprakash

    2016-01-20

    The role of pre-existing immunity for influenza vaccine responses is of great importance for public health, and thus has been studied in various contexts, yet the impact of differential priming on vaccine responses in the midst of antigenic drift remains to be elucidated. To address this with antigenically related viruses, mice were first primed by either infection or immunization with A/Puerto Rico/8/34 (PR8) virus, then immunized with whole-inactivated A/Fort Monmouth/1/47 (FM1) virus. The ensuing vaccine responses and the protective efficacy of FM1 were superior in PR8 infection-primed mice compared to PR8 immunization-primed or unprimed mice. Increased FM1-specific Ab responses of PR8 infection-primed mice also broadened cross-reactivity against contemporary as well as antigenically more drifted strains. Further, prior infection heightened the protective efficacy of antigenically distant strains, such as A/Brisbane/59/2006 infection followed by immunization with split pandemic H1N1 vaccine (A/California/07/2009). Therefore, influenza infection is a significant priming event that intensifies future vaccine responses against drift strains. Published by Elsevier Ltd.

  13. A Meningococcal NOMV-FHbp Vaccine for Africa Elicits Broader Serum Bactericidal Antibody Responses Against Serogroup B and non-B Strains than a Licensed Serogroup B Vaccine

    PubMed Central

    Pajon, Rolando; Lujan, Eduardo; Granoff, Dan M.

    2016-01-01

    Background Meningococcal epidemics in Sub-Sahara caused by serogroup A strains are controlled by a group A polysaccharide conjugate vaccine. Strains with serogroups C, W and X continue to cause epidemics. Protein antigens in licensed serogroup B vaccines are shared among serogroup B and non-B strains. Purpose Compare serum bactericidal antibody responses elicited by an investigational native outer membrane vesicle vaccine with over-expressed Factor H binding protein (NOMV-FHbp) and a licensed serogroup B vaccine (MenB-4C) against African serogroup A, B, C, W and X strains. Methods Human Factor H (FH) transgenic mice were immunized with NOMV-FHbp prepared from a mutant African meningococcal strain containing genetically attenuated endotoxin and a mutant sub-family B FHbp antigen with low FH binding, or with MenB-4C, which contains a recombinant sub-family B FHbp antigen that binds human FH, and three other antigens, NHba, NadA and PorA P1.4, capable of eliciting bactericidal antibody. Results The NOMV-FHbp elicited serum bactericidal activity against 12 of 13 serogroup A, B, W or X strains from Africa, and four isogenic serogroup B mutants with subfamily B FHbp sequence variants. There was no activity against a serogroup B mutant with sub-family A FHbp, or two serogroup C isolates from a recent outbreak in Northern Nigeria, which were mismatched for both PorA and sub-family of the FHbp vaccine antigen. For MenB-4C, NHba was expressed by all 16 African isolates tested, FHbp sub-family B in 13, and NadA in five. However, MenB-4C elicited titers ≥1:10 against only one isolate, and against only two of four serogroup B mutant strains with sub-family B FHbp sequence variants. Conclusions NOMV-FHbp has greater potential to confer serogroup-independent protection in Africa than the licensed MenB-4C vaccine. However, the NOMV-FHbp vaccine will require inclusion of sub-family A FHbp for coverage against recent serogroup C strains causing outbreaks in Northern Nigeria. PMID

  14. An Improved Vaccine for Prevention of Respiratory Tularemia Caused by Francisella tularensis SchuS4 Strain

    PubMed Central

    Bakshi, Chandra Shekhar; Malik, Meenakshi; Mahawar, Manish; Kirimanjeswara, Girish S.; Hazlett, Karsten R. O.; Palmer, Lance E.; Furie, Martha B.; Singh, Rajendra; Melendez, J. Andres; Sellati, Timothy J.; Metzger, Dennis W.

    2008-01-01

    Vaccination of mice with Francisella tularensis live vaccine strain (LVS) mutants described so far have failed to induce protection in C57BL/6 mice against challenge with the virulent strain F. tularensis SchuS4. We previously have reported that a mutant of F. tularensis LVS deficient in iron superoxide dismutase (sodBFt) is hypersensitive to oxidative stress and attenuated for virulence in mice. Herein, we evaluated the efficacy of this mutant as a vaccine candidate against respiratory tularemia caused by F. tularensis SchuS4. C57BL/6 mice were vaccinated intranasally (i.n.) with the sodBFt mutant and challenged i.n. with lethal doses of F. tularensis SchuS4. The level of protection against SchuS4 challenge was higher in sodBFt vaccinated group as compared to the LVS vaccinated mice. SodBFt vaccinated mice following SchuS4 challenge exhibited significantly reduced bacterial burden in lungs, liver and spleen, regulated production of pro-inflammatory cytokines and less severe histopathological lesions compared to the LVS vaccinated mice. The sodBFt vaccination induced a potent humoral immune response and protection against SchuS4 required both CD4 and CD8 T cells in the vaccinated mice. SodBFt mutants revealed upregulated levels of chaperonine proteins DnaK, GroEL and Bfr that have been shown to be important for generation of a potent immune response against Francisella infection. Collectively, this study describes an improved live vaccine candidate against respiratory tularemia that has an attenuated virulence and enhanced protective efficacy than the LVS. PMID:18692537

  15. Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain.

    PubMed

    Garg, Rajni; Kaur, Manpreet; Saxena, Ankur; Prasad, Rajendra; Bhatnagar, Rakesh

    2017-03-03

    Rabies is a serious concern world-wide. Despite availability of rabies vaccines for long; their efficacy, safety, availability and cost effectiveness has been a tremendous issue. This calls for improvement of rabies vaccination strategies. DNA vaccination has immense potential in this regard. The DNA vaccine pgp.LAMP-1 conferred 60% protection to BALB/c mice against 20 LD50 rabies challenge virus standard (CVS) strain challenge. Upon supplementation with Emulsigen-D, the vaccine formulation conferred complete protection against lethal challenge. To assess the feasibility of this vaccine formulation for human use, it was tested along with other FDA approved adjuvants, namely, Alum, Immuvac, Montanide ISA720 VG. Enhanced immune response correlated with high IgG antibody titer, Th2 biased response with a high level of rabies virus neutralizing antibodies (RVNAs) and IgG1/IgG2a ratio >1, observed upon alum supplementation of the rabies DNA vaccine. The total IgG antibody titer was 2IU/ml and total RVNA titer was observed to be 4IU/ml which is eight times higher than the minimum protective titer recommended by WHO. Furthermore, it conferred 80% protection against challenge with 50 LD50 of the rabies CVS strain, conducted in compliance with the potency test for rabies recommended by the National Institutes of Health (NIH), USA. Previously, we have established pre-clinical safety of this vaccine as per the guidelines of Schedule Y, FDA as well as The European Agency for evaluation of Medicinal Products. The vaccine showed no observable toxicity at the site of injection as well as at systemic level in Wistar rats when administered with 10X recommended dose. Therefore, supplementation of rabies DNA vaccine, pgp.LAMP-1 with alum would lead to development of a non-toxic, efficacious, stable and affordable vaccine that can be used to combat high numbers of fatal rabies infections tormenting developing countries.

  16. A comparison of monovalent Hong Kong influenza virus vaccine with vaccines containing only pre-1968 Asian strains in adult volunteers. A report to the Medical Research Council Committee on Influenza and other Respiratory Virus Vaccines.

    PubMed

    Hobson, D; Baker, F A; Chivers, C P; Reed, S E; Sharp, D

    1970-09-01

    A total of 1601 adult industrial workers were vaccinated with either monovalent inactivated vaccine of the Hong Kong strain of influenza A virus, or with polyvalent vaccine containing only pre-1968 Asian viruses. Serological investigations on a random sample of volunteers showed that 53/56 (95%) given Hong Kong vaccine developed a significant rise in specific haemagglutination-inhibiting antibody; final titres were 1/48 or greater in 39 (70%) and the GMT (geometric mean titre) was 96.5. After polyvalent Asian vaccine, 40/67 (60%) also produced antibody against Hong Kong virus, but only 21 (31%) had final titres of 1/48 or above, and the GMT rose only to 14.1. An intranasal spray of the Hong Kong vaccine in addition to injected Asian vaccine gave no additional increase in antibody.Each type of vaccine stimulated a recall of pre-existing antibody against Asian viruses. The possible significance of heterologous responses to the two vaccines is discussed.The incidence of clinical influenza in the trial population was sporadic, and the infection rates were too low to allow any accurate estimate of the protective efficiency of the two vaccines.

  17. Changing epidemiology of invasive Haemophilus influenzae in Ontario, Canada: evidence for herd effects and strain replacement due to Hib vaccination.

    PubMed

    Adam, H J; Richardson, S E; Jamieson, F B; Rawte, P; Low, D E; Fisman, D N

    2010-05-28

    The epidemiology of invasive Haemophilus influenzae infections was evaluated in Ontario between 1989 and 2007 to assess the impact of the introduction of the conjugate H. influenzae serotype b (Hib) vaccine in the early 1990 s on Hib and non-Hib serotypes in both vaccinated and unvaccinated cohorts as well as the possibility of "strain replacement" with non-vaccine H. influenzae strains. Data were collected by the provincial Public Health Laboratories-Toronto, Ontario Agency for Health Protection and Promotion, which performed almost all serotyping on invasive (blood, CSF, other sterile sites) H. influenzae strains isolated in the province during the study period. Temporal trends for Hib, other typeable strains, and non-typeable H. influenzae were evaluated by Poisson regression, controlling for the specimen submissions. Prior to infant Hib vaccination, the most commonly observed serotype was serotype b (64.9%). Subsequently, 70.3%, 13.6%, and 9.4% of isolates were non-typeable, serotype f, and serotype b, respectively. Infant Hib vaccination resulted in a decrease in Hib incidence in all age groups (pooled IRR 0.432) and marked increases of non-typeable and serotype f H. influenzae in children aged <5 years (IRR 2.4 and 3.0, respectively). Vaccination against Hib has altered the epidemiology of invasive H. influenzae infections in Ontario. Prevention of invasive Hib disease was observed in both vaccinated and unvaccinated age groups. Invasive H. influenzae infection now commonly presents as sepsis due to non-typeable H. influenzae in older individuals. However, strain replacement of Hib with serotype f and non-typeable strains in children under 5 years was documented.

  18. Factors associated with occupational strain among Chinese teachers: a cross-sectional study.

    PubMed

    Yang, X; Wang, L; Ge, C; Hu, B; Chi, T

    2011-02-01

    With the reform of the education system in China, teachers are suffering from more occupational strain, which is believed to impair their working state indirectly and affect their health. This study assessed occupational strain and explored the related factors among Chinese teachers. Cross-sectional with cluster sampling. The study population was composed of 3570 school teachers working in 64 primary and middle schools in Heping District in Shenyang, China. Data were collected using a self-administered questionnaire (the Chinese version of the Occupational Stress Inventory scale). Multivariate linear regression analyses were performed to study the factors related to occupational strain. The average score on the Personal Strain Questionnaire (PSQ) for the whole study population was 106.5 (107.5 in men and 106.3 in women). Teachers with chronic disease, a greater number of days of sick leave, recent experience of a stressful life event and divorced/separated/widowed status tended to suffer greater strain than their peers. Regression analyses showed that the PSQ score was significantly associated with role overload, role boundary, responsibility and physical environment, and inversely associated with recreation and rational coping. The most crucial predictors of occupational strain were chronic disease, days of sick leave, recent experience of a stressful life event and marital status. Being a class teacher was the strongest indicator of interpersonal strain. Self-care was associated with vocational strain and psychological strain, and inversely associated with physical strain. Most teachers in this study experienced a high degree of occupational strain. Chronic disease, days of sick leave, recent experience of a stressful life event and divorced/separated/widowed status played prominent roles in occupational strain. In addition, role overload, role boundary, responsibility and physical environment induce occupational strain, while recreation and rational coping have

  19. Effects of time-specific F-strain Mycoplasma gallisepticum inoculation overlays on prelay ts-11-strain M. gallisepticum vaccination on blood characteristics of commercial laying hens.

    PubMed

    Peebles, E D; Vance, A M; Branton, S L; Collier, S D; Gerard, P D

    2009-05-01

    Two trials were conducted to determine the effects of a prelay ts-11-strain Mycoplasma gallisepticum (ts-11MG) vaccination alone or in combination with subsequent time-specific F-strain M. gallisepticum (FMG) inoculations on the blood characteristics of commercial laying hens. The following 4 treatments were utilized: 1) sham vaccination at 10 wk of age, 2) vaccination of ts-11MG at 10 wk, 3) ts-11MG at 10 wk overlaid by FMG inoculation at 22 wk, and 4) ts-11MG at 10 wk overlaid by FMG at 45 wk. Parameters measured in both trials were whole blood hematocrit, plasma protein, serum cholesterol, serum triglycerides, and serum calcium. No significant age x treatment interactions and no significant age or treatment main effects were observed for any of the blood parameters investigated, except for serum calcium. At wk 22, serum calcium concentrations were increased by vaccination with ts-11MG at 10 wk, and levels were further increased when the ts-11MG vaccination at 10 wk was overlaid by an FMG inoculation at 22 wk. These results suggest that ts-11MG vaccination at 10 wk of age alone or combined with F-strain inoculum overlays at either 22 or 45 wk may be used without any consequential effects on hematocrit or the lipid and protein levels in the blood of commercial layers. Because elevations in serum calcium were not associated with changes in hen performance, as reported in a previous companion article, it is further suggested that prelay ts-11MG vaccination before FMG inoculation overlays during lay may provide adequate protection against field strain M. gallisepticum infections while being innocuous to layer performance.

  20. Strain-specific Plasmodium falciparum growth inhibition among Malian children immunized with a blood-stage malaria vaccine.

    PubMed

    Laurens, Matthew B; Kouriba, Bourema; Bergmann-Leitner, Elke; Angov, Evelina; Coulibaly, Drissa; Diarra, Issa; Daou, Modibo; Niangaly, Amadou; Blackwelder, William C; Wu, Yukun; Cohen, Joe; Ballou, W Ripley; Vekemans, Johan; Lanar, David E; Dutta, Sheetij; Diggs, Carter; Soisson, Lorraine; Heppner, D Gray; Doumbo, Ogobara K; Plowe, Christopher V; Thera, Mahamadou A

    2017-01-01

    The blood-stage malaria vaccine FMP2.1/AS02A, comprised of recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) and the adjuvant system AS02A, had strain-specific efficacy against clinical malaria caused by P. falciparum with the vaccine strain 3D7 AMA1 sequence. To evaluate a potential correlate of protection, we measured the ability of participant sera to inhibit growth of 3D7 and FVO strains in vitro using high-throughput growth inhibition assay (GIA) testing. Sera from 400 children randomized to receive either malaria vaccine or a control rabies vaccine were assessed at baseline and over two annual malaria transmission seasons after immunization. Baseline GIA against vaccine strain 3D7 and FVO strain was similar in both groups, but more children in the malaria vaccine group than in the control group had 3D7 and FVO GIA activity ≥15% 30 days after the last vaccination (day 90) (49% vs. 16%, p<0.0001; and 71.8% vs. 60.4%, p = 0.02). From baseline to day 90, 3D7 GIA in the vaccine group was 7.4 times the mean increase in the control group (p<0.0001). In AMA1 vaccinees, 3D7 GIA activity subsequently returned to baseline one year after vaccination (day 364) and did not correlate with efficacy in the extended efficacy time period to day 730. In Cox proportional hazards regression models with time-varying covariates, there was a slight suggestion of an association between 3D7 GIA activity and increased risk of clinical malaria between day 90 and day 240. We conclude that vaccination with this AMA1-based malaria vaccine increased inhibition of parasite growth, but this increase was not associated with allele-specific efficacy in the first malaria season. These results provide a framework for testing functional immune correlates of protection against clinical malaria in field trials, and will help to guide similar analyses for next-generation malaria vaccines. Clinical trials registry: This clinical trial was registered on clinicaltrials.gov, registry

  1. Strain-specific Plasmodium falciparum growth inhibition among Malian children immunized with a blood-stage malaria vaccine

    PubMed Central

    Kouriba, Bourema; Bergmann-Leitner, Elke; Angov, Evelina; Coulibaly, Drissa; Diarra, Issa; Daou, Modibo; Niangaly, Amadou; Blackwelder, William C.; Wu, Yukun; Cohen, Joe; Ballou, W. Ripley; Vekemans, Johan; Lanar, David E.; Dutta, Sheetij; Diggs, Carter; Soisson, Lorraine; Heppner, D. Gray; Doumbo, Ogobara K.; Plowe, Christopher V.; Thera, Mahamadou A.

    2017-01-01

    The blood-stage malaria vaccine FMP2.1/AS02A, comprised of recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) and the adjuvant system AS02A, had strain-specific efficacy against clinical malaria caused by P. falciparum with the vaccine strain 3D7 AMA1 sequence. To evaluate a potential correlate of protection, we measured the ability of participant sera to inhibit growth of 3D7 and FVO strains in vitro using high-throughput growth inhibition assay (GIA) testing. Sera from 400 children randomized to receive either malaria vaccine or a control rabies vaccine were assessed at baseline and over two annual malaria transmission seasons after immunization. Baseline GIA against vaccine strain 3D7 and FVO strain was similar in both groups, but more children in the malaria vaccine group than in the control group had 3D7 and FVO GIA activity ≥15% 30 days after the last vaccination (day 90) (49% vs. 16%, p<0.0001; and 71.8% vs. 60.4%, p = 0.02). From baseline to day 90, 3D7 GIA in the vaccine group was 7.4 times the mean increase in the control group (p<0.0001). In AMA1 vaccinees, 3D7 GIA activity subsequently returned to baseline one year after vaccination (day 364) and did not correlate with efficacy in the extended efficacy time period to day 730. In Cox proportional hazards regression models with time-varying covariates, there was a slight suggestion of an association between 3D7 GIA activity and increased risk of clinical malaria between day 90 and day 240. We conclude that vaccination with this AMA1-based malaria vaccine increased inhibition of parasite growth, but this increase was not associated with allele-specific efficacy in the first malaria season. These results provide a framework for testing functional immune correlates of protection against clinical malaria in field trials, and will help to guide similar analyses for next-generation malaria vaccines. Clinical trials registry: This clinical trial was registered on clinicaltrials.gov, registry

  2. A comparison of biological characteristics of three strains of Chinese sacbrood virus in Apis cerana

    PubMed Central

    Hu, Ying; Fei, Dongliang; Jiang, Lili; Wei, Dong; Li, Fangbing; Diao, Qingyun; Ma, Mingxiao

    2016-01-01

    We selected and sequenced the entire genomes of three strains of Chinese sacbrood virus (CSBV): LNQY-2008 (isolated in Qingyuan, Liaoning Province), SXYL-2015 (isolated in Yulin, Shanxi Province), and JLCBS-2014 (isolated in Changbaishan, Jilin Province), by VP1 amino acid (aa) analysis. These strains are endemic in China and infect Apis cerana. Nucleotide sequences, deduced amino acid sequences, genetic backgrounds, and other molecular biological characteristics were analysed. We also examined sensitivity of these virus strains to temperature, pH, and organic solvents, as well as to other physicochemical properties. On the basis of these observations, we compared pathogenicity and tested cross-immunogenicity and protective immunity, using antisera raised against each of the three strains. Our results showed that compared with SXYL-2015, LNQY-2008 has a 10-aa deletion and 3-aa deletion (positions 282–291 and 299–301, respectively), whereas JLCBS-2014 has a 17-aa deletion (positions 284–300). However, the three strains showed no obvious differences in physicochemical properties or pathogenicity. Moreover, there was immune cross-reactivity among the antisera raised against the different strains, implying good protective effects of such antisera. The present study should significantly advance the understanding of the pathogenesis of Chinese sacbrood disease, and offers insights into comprehensive prevention and treatment of, as well as possible protection from, the disease by means of an antiserum. PMID:27853294

  3. Monovalent rotavirus vaccine provides protection against an emerging fully heterotypic G9P[4] rotavirus strain in Mexico.

    PubMed

    Yen, Catherine; Figueroa, Jesùs Reyna; Uribe, Edgar Sánchez; Carmen-Hernández, Luz Del; Tate, Jacqueline E; Parashar, Umesh D; Patel, Manish M; Richardson López-Collado, Vesta

    2011-09-01

    After the introduction of monovalent rotavirus vaccine (RV1) in Mexico in 2006-2007, diarrhea mortality and morbidity declined substantially among Mexican children under 5 years of age. In January 2010, surveillance identified the emergence of a novel G9P[4] rotavirus strain nationwide. We conducted a case-control study to assess the field effectiveness of RV1 against severe rotavirus gastroenteritis caused by this unusual strain and to determine whether the G9P[4] emergence was related to vaccine failure or failure to vaccinate. RV1 was 94% effective (95% confidence interval, 16%-100%) against G9P[4] rotavirus-related hospitalization, indicating that its emergence was likely unrelated to vaccine pressure.

  4. Social strain, couple dynamics and gender differences in gambling problems: evidence from Chinese married couples.

    PubMed

    Cheung, Nicole W T

    2015-02-01

    Knowledge of the influence of couple dynamics on gender differences in gambling behavior remains meager. Building on general strain theory from the sociology of deviance and stress crossover theory from social psychology, we argue that the strain encountered by one partner in a social setting may affect his or her spouse. For instance, the wife of a man under more social strain may experience more strain in turn and thus be at a higher risk of developing disordered gambling than the wife of a man under less social strain. Using community survey data of 1620 Chinese married couples, we performed multilevel dyad analyses to address social strain and couple dynamics, in addition to their roles as predictors of gambling behavior in both spouses. This was a community survey of Hong Kong and therefore was not representative of China. Based on the DSM-IV screen, the rates of probable problem gambling and pathological gambling among male partners (12.8% vs. 2.5%) were twice those among female partners (5.2% vs. 0.3%). We also found that the social strain experienced by a male partner significantly predicted both his and his wife's likelihood of developing gambling problems. Although a female partner's exposure to social strain was a significant correlate of her gambling problem, it had no significant association with her husband's gambling behavior. These results suggest that the cross-spouse transference of social strain may be a gendered process. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Immunogenicity differences of a 15-valent pneumococcal polysaccharide conjugate vaccine (PCV15) based on vaccine dose, route of immunization and mouse strain.

    PubMed

    Caro-Aguilar, Ivette; Indrawati, Lani; Kaufhold, Robin M; Gaunt, Christine; Zhang, Yuhua; Nawrocki, Denise K; Giovarelli, Cecilia; Winters, Michael A; Smith, William J; Heinrichs, Jon; Skinner, Julie M

    2017-02-07

    Pneumococcal disease continues to be a medical need even with very effective vaccines on the market. Globally, there are extensive research efforts to improve serotype coverage with novel vaccines; therefore, conducting preclinical studies in different animal models becomes essential. The work presented herein focuses on evaluating a 15-valent pneumococcal conjugate vaccine (PCV15) in mice. Initially we evaluated several doses of PCV15 in Balb/c mice. The optimal vaccine dose was determined to be 0.4μg per pneumococcal polysaccharide (PS) (0.8μg of 6B) for subsequent studies. This PS dose was chosen for PCV evaluation in mice based on antibody levels determined by multiplexed electrochemiluminescent (ECL) assays, T-cell responses following in vitro stimulation with CRM197 peptides and protection from pneumococcal challenge. We then selected four mouse strains for evaluation: Balb/c, C3H/HeN, CD1 and Swiss Webster (SW), immunized with PCV15 by either intraperitoneal (IP) or intramuscular (IM) routes. We assessed IgG responses by ECL assays and functional antibody activity by multiplexed opsonophagocytic assays (MOPA). Every mouse strain evaluated responded to all 15 serotypes contained in the vaccine. Mice tended to have lower responses to serotypes 6B, 23F and 33F. The IP route of immunization resulted in higher antibody titers for most serotypes in Balb/c, C3H and SW. CD1 mice tended to respond similarly for most serotypes, regardless of route of immunization. Similar trends were observed with the four mouse strains when evaluating functional antibody activity. Given the differences in antibody responses based on mouse strain and route of immunization, it is critical to evaluate pneumococcal vaccines in multiple animal models to determine the optimal formulation before moving to clinical trials.

  6. The function of PlcR in Bacillus anthracis vaccine strain A16R.

    PubMed

    Xiaolin, Jia; Dongshu, Wang; Zhiqi, Gao; Erling, Feng; Jiping, Zheng; Hengliang, Wang; Guiying, Guo; Xiankai, Liu

    2015-05-01

    Bacillus anthracis, B. thuringiensis and B. cereus are members of the B. cereus group. They share high genetic similarity. Whereas plcR (Phospholipase C regulator) usually encodes a functional pleiotropic activator protein in B. cereus and B. thuringiensis isolates, a characteristic nonsense mutation is found in all B. anthracis strains investigated, making the gene dysfunctional. To study the function of PlcR in B. anthracis, we used the B. cereus CMCC63301 genome as a template and constructed a recombinant expression plasmid pBE2A-plcR, and introduced it into the B. anthracis vaccine strain A16R, and then analyzed the activity of the hemolysin and sphingomyelinase. The results showed that transformation of B. anthracis with plasmid pBE2A-plcR carrying the native B. cereus plcR gene active the expression of sphingomyelinase gene, but did not activate expression of hemolysin genes of B. anthracis A16R.

  7. Excretion of Brucella abortus vaccine B19 strain during a reproductive cycle in dairy cows

    PubMed Central

    Pacheco, W. A.; Genovez, M. E.; Pozzi, C. R.; Silva, L. M. P.; Azevedo, S. S.; Did, C. C.; Piatti, R. M.; Pinheiro, E. S.; Castro, V.; Miyashiro, S.; Gambarini, M. L.

    2012-01-01

    This paper aimed to determine the excretion period of B19 vaccine strain during a complete reproductive cycle (from estrus synchronization, artificial insemination, pregnancy and until 30 days after parturition) of dairy cows from 3 to 9 years old that were previously vaccinated from 3 to 8 months. Three groups were monitored with monthly milk and urine collection during 12 months: G1 with seven cows from 3 to 4 years old; G2 with three cows from 5 to 6 years old; and G3 with four cows from 7 to 9 years old. Urine and milk samples were submitted to bacteriological culture and urine and PCR reactions for detection of Brucella spp. and PCR-multiplex for B19 strain identification. Ring test (RT) was also performed in the milk samples, and serum samples were tested by buffered acidified plate antigen test (BAPA). All animals were serologically negative at BAPA and Brucella spp. was not isolated from both urine and milk samples. RT revealed 13/210 (6.2%) positive milk samples. PCR reactions detected DNA of Brucella spp. in 86/420 (20.5%) samples. In urine it was found a significantly higher frequency (35.2%; 74/210) than in milk (5.7%; 12/210), more frequently from the estrus to 150 days of pregnancy and after parturition (6.7%; 10/150), and from 150 days of pregnancy to parturition (3.4%; 2/60), and they were all identified as B19 strain. In three groups, intermittent excretion of B19 strain was detected mainly in urine samples, which confirmed its multiplication and persistence in cows for until 9 years. PMID:24031869

  8. Excretion of Brucella abortus vaccine B19 strain during a reproductive cycle in dairy cows.

    PubMed

    Pacheco, W A; Genovez, M E; Pozzi, C R; Silva, L M P; Azevedo, S S; Did, C C; Piatti, R M; Pinheiro, E S; Castro, V; Miyashiro, S; Gambarini, M L

    2012-04-01

    This paper aimed to determine the excretion period of B19 vaccine strain during a complete reproductive cycle (from estrus synchronization, artificial insemination, pregnancy and until 30 days after parturition) of dairy cows from 3 to 9 years old that were previously vaccinated from 3 to 8 months. Three groups were monitored with monthly milk and urine collection during 12 months: G1 with seven cows from 3 to 4 years old; G2 with three cows from 5 to 6 years old; and G3 with four cows from 7 to 9 years old. Urine and milk samples were submitted to bacteriological culture and urine and PCR reactions for detection of Brucella spp. and PCR-multiplex for B19 strain identification. Ring test (RT) was also performed in the milk samples, and serum samples were tested by buffered acidified plate antigen test (BAPA). All animals were serologically negative at BAPA and Brucella spp. was not isolated from both urine and milk samples. RT revealed 13/210 (6.2%) positive milk samples. PCR reactions detected DNA of Brucella spp. in 86/420 (20.5%) samples. In urine it was found a significantly higher frequency (35.2%; 74/210) than in milk (5.7%; 12/210), more frequently from the estrus to 150 days of pregnancy and after parturition (6.7%; 10/150), and from 150 days of pregnancy to parturition (3.4%; 2/60), and they were all identified as B19 strain. In three groups, intermittent excretion of B19 strain was detected mainly in urine samples, which confirmed its multiplication and persistence in cows for until 9 years.

  9. The pathogenic and vaccine strains of equine infectious anemia virus differentially induce cytokine and chemokine expression and apoptosis in macrophages.

    PubMed

    Lin, Yue-Zhi; Cao, Xue-Zhi; Li, Liang; Li, Li; Jiang, Cheng-Gang; Wang, Xue-Feng; Ma, Jian; Zhou, Jian-Hua

    2011-09-01

    The attenuated equine infectious anemia virus (EIAV) vaccine was the first attenuated lentivirus vaccine to be used in a large-scale application and has been used to successfully control the spread of equine infectious anemia (EIA) in China. To better understand the potential role of cytokines in the pathogenesis of EIAV infection and resulting immune response, we used branched DNA technology to compare the mRNA expression levels of 12 cytokines and chemokines, including IL-1α, IL-1β, IL-4, IL-10, TNF-α, IFN-γ, IP-10, IL-8, MIP-1α, MIP-1β, MCP-1, and MCP-2, in equine monocyte-derived macrophages (eMDMs) infected with the EIAV(DLV121) vaccine strain or the parental EIAV(DLV34) pathogenic strain. Infection with EIAV(DLV34) and EIAV(DLV121) both caused changes in the mRNA levels of various cytokines and chemokines in eMDMs. In the early stage of infection with EIAV(DLV34) (0-24h), the expression of the pro-inflammatory cytokines TNF-α and IL-1β were significantly up-regulated, while with EIAV(DLV121), expression of the anti-inflammatory cytokine IL-4 was markedly up-regulated. The effects on the expression of other cytokines and chemokines were similar between these two strains of virus. During the first 4 days after infection, the expression level of IL-4 in cells infected with the pathogenic strain were significantly higher than that in cells infected with the vaccine strain, but the expression of IL-1α and IL-1β induced by the vaccine strain was significantly higher than that observed with the pathogenic strain. In addition, after 4 days of infection with the pathogenic strain, the expression levels of 5 chemokines, but not IP-10, were markedly increased in eMDMs. In contrast, the vaccine strain did not up-regulate these chemokines to this level. Contrary to our expectation, induced apoptosis in eMDMs infected with the vaccine strain was significantly higher than that infected with the pathogenic strain 4 days and 6 days after infection. Together, these

  10. Vaccination with cell immunoglobulin mucin-1 antibodies and inactivated influenza enhances vaccine-specific lymphocyte proliferation, interferon-γ production and cross-strain reactivity

    PubMed Central

    Soo Hoo, W; Jensen, E R; Saadat, A; Nieto, D; Moss, R B; Carlo, D J; Moll, T

    2006-01-01

    Influenza virus causes a contagious and potentially serious infection of the upper respiratory tract. While neutralizing antibodies are protective against infection, the problem of antigenic drift remains, requiring the constant monitoring and development of new vaccines. The magnitude of this situation is underscored by the emergence of new potentially human pathogenic influenza strains, avian H5N1 being the most recent example. We present evidence that antibodies against T cell immunoglobulin mucin-1 (TIM-1), a recently identified immunomodulatory molecule, stimulate cellular immunity against influenza viruses and cross-strain immune reactivity. To determine potential immunostimulatory properties of anti-TIM-1, mice were vaccinated with inactivated influenza virus in the presence or absence of TIM-1-specific monoclonal antibodies. Development of cellular immunity against both the influenza strain used for immunization and serotypically distinct virus strains was monitored 3 weeks after vaccination by determining antigen-specific lymphocyte proliferation and cytokine production. Results show that TIM-1 antibodies enhance antigen-specific cellular proliferation (P < 0·05) and interferon (IFN)-γ production (P < 0·01). Using blocking anti-CD4 and CD8 antibodies, it was observed that antigen-specific cellular proliferation is CD4-dependent and that the majority of proliferating cells are CD4+. Finally, vaccination with inactivated influenza virus with TIM-1 antibody results in the significant (P < 0·001) induction of proliferation and IFN-γ production upon stimulation with one of three serologically distinct strains. TIM-1 antibodies demonstrate an adjuvant effect promoting antigen-specific cellular proliferation and IFN-γ production, which are important for the promotion of cell-mediated immunity. These results are the first to suggest that TIM-1 antibody may serve as a potent adjuvant in the development of new influenza virus vaccines. PMID:16792682

  11. [History of development of the live poliomyelitis vaccine from Sabin attenuated strains in 1959 and idea of poliomyelitis eradication].

    PubMed

    Lashkevich, V A

    2013-01-01

    In 1958 Poliomyelitis Institute in Moscow and Institute of Experimental Medicine in St. Petersburg received from A. Sabin the attenuated strains of poliomyelitis virus. The characteristics of the strains were thoroughly studied by A. A. Smorodintsev and coworkers. They found that the virulence of the strains fluctuated slightly in 10 consecutive passages through the intestine of the non-immune children. A part of the Sabin material was used by A. A. Smorodintsev and M. P. Chumakov in the beginning of 1959 for immunizing approximately 40000 children in Estonia, Lithuania, and Latvia. Epidemic poliomyelitis rate in these republics decreased from approximately 1000 cases yearly before vaccination to less than 20 in the third quarter of 1959. This was a convincing proof of the efficacy and safety of the vaccine from the attenuated Sabin strains. In 1959, according to A. Sabin's recommendation, a technology of live vaccine production was developed at the Poliomyelitis Institute, and several experimental lots of vaccine were prepared. In the second part of 1959, 13.5 million children in USSR were immunized. The epidemic poliomyelitis rate decreased 3-5 times in different regions without paralytic cases, which could be attributed to the vaccination. These results were the final proof of high efficiency and safety of live poliomyelitis vaccine from the attenuated Sabin strains. Based on these results, A. Sabin and M. P. Chumakov suggested in 1960 the idea of poliomyelitis eradication using mass immunization of children with live vaccine. 72 million persons up to 20 years old were vaccinated in USSR in 1960 with a 5 times drop in the paralytic rate. 50-year-long use of live vaccine results in poliomyelitis eradication in almost all countries worldwide. More than 10 million children were rescued from the death and palsy. Poliomyelitis eradication in a few countries where it still exists depends not on medical services but is defined by the attitude of their leaders to fight

  12. T-bet Regulates Immunity to Francisella tularensis Live Vaccine Strain Infection, Particularly in Lungs

    PubMed Central

    Melillo, Amanda A.; Foreman, Oded; Bosio, Catharine M.

    2014-01-01

    Upregulation of the transcription factor T-bet is correlated with the strength of protection against secondary challenge with the live vaccine strain (LVS) of Francisella tularensis. Thus, to determine if this mediator had direct consequences in immunity to LVS, we examined its role in infection. Despite substantial in vivo gamma interferon (IFN-γ) levels, T-bet-knockout (KO) mice infected intradermally (i.d.) or intranasally (i.n.) with LVS succumbed to infection with doses 2 log units less than those required for their wild-type (WT) counterparts, and exhibited significantly increased bacterial burdens in the lung and spleen. Lungs of LVS-infected T-bet-KO mice contained fewer lymphocytes and more neutrophils and interleukin-17 than WT mice. LVS-vaccinated T-bet-KO mice survived lethal LVS intraperitoneal secondary challenge but not high doses of LVS i.n. challenge, independently of the route of vaccination. Immune T lymphocytes from the spleens of i.d. LVS-vaccinated WT or KO mice controlled intracellular bacterial replication in an in vitro coculture system, but cultures with T-bet-KO splenocyte supernatants contained less IFN-γ and increased amounts of tumor necrosis factor alpha. In contrast, immune T-bet-KO lung lymphocytes were greatly impaired in controlling intramacrophage growth of LVS; this functional defect is the likely mechanism underpinning the lack of respiratory protection. Taken together, T-bet is important in host resistance to primary LVS infection and i.n. secondary challenge. Thus, T-bet represents a true, useful correlate for immunity to LVS. PMID:24421047

  13. Factors influencing preclinical in vivo evaluation of mumps vaccine strain immunogenicity

    PubMed Central

    Halassy, B; Kurtović, T; Brgles, M; Lang Balija, M; Forčić, D

    2015-01-01

    Immunogenicity testing in animals is a necessary preclinical assay for demonstration of vaccine efficacy the results of which are often the basis for the decision whether to proceed or withdraw the further development of the novel vaccine candidate. However, in vivo assays are rarely, if at all, optimized and validated. Here we clearly demonstrate the importance of in vivo assay (mumps virus immunogenicity testing in guinea pigs) optimization for gaining reliable results and the suitability of Fractional factorial design of experiments (DoE) for such a purpose. By the use of DoE with resolution IV (2IV(4-1)) we clearly revealed that the parameters significantly increasing assay sensitivity were interval between animal immunizations followed by the body weight of experimental animals. The quantity (0 versus 2%) of the stabilizer (fetal bovine serum, FBS) in the sample was shown as non-influencing parameter in DoE setup. However, the separate experiment investigating only the FBS influence, and performed under other parameters optimally set, showed that FBS also influences the results of immunogenicity assay. Such finding indicated that (a) factors with strong influence on the measured outcome can hide the effects of parameters with modest/low influence and (b) the matrix of mumps virus samples to be compared for immunogenicity must be identical for reliable virus immunogenicity comparison. Finally the 3 mumps vaccine strains widely used for decades in the licensed vaccines were for the first time compared in an animal model, and results obtained were in line with their reported immunogenicity in human population supporting the predictive power of the optimized in vivo assay. PMID:26376015

  14. Salmonella abortusovis, strain Rv6, a new vaccinal vehicle for small ruminants.

    PubMed

    Bourgogne, A; Sanchis, R; Clément, J M; Pépin, M

    1998-03-31

    Salmonella abortusovis strain Rv6 (Sao Rv6) is a live attenuated vaccine used for a few years to protect ewes against abortive salmonellosis. As Salmonellae, particularly Salmonella aro mutants, have considerable potential as vehicles for the presentation of heterologous vaccine antigens, Sao Rv6 was tested in order to develop a vaccinal vehicle for small ruminants. Five vector plasmids were tested in Sao Rv6; these plasmids, which carry Maltose Binding Protein (MBP) expressed as protein, but differ in their promotors, had been previously tested in S. typhimurium strain SL3261, and were transferred into Sao Rv6. The five plasmids were stable in vitro, and the recombinant Sao Rv6 expressed MBP at various levels. Intraperitoneal infection of OF1 mice with the recombinant bacteria did not modify the characteristics of Sao Rv6; dissemination and infection levels were similar in all groups and all mice developed antibodies to Salmonella antigens as measured by ELISA. In contrast, only animals immunized with Sao Rv6 carrying the pNTE plasmid developed a serum antibody response to MBP. This plasmid was then tested in sheep; following subcutaneous immunization with Sao Rv6-pNTE, dissemination and infection levels were not modified in comparison with sheep immunized with Sao Rv6 lacking plasmid. Antibodies specific to MBP were detected in sera of sheep immunized with Sao Rv6-pNTE, purified MBP, and with S. typhimurium SL3261-pNTE as positive controls. These results demonstrate that Sao Rv6 can be used as a vehicle for heterologous antigens in sheep with pNTE as plasmid vector.

  15. A multi-center survey of age of sexual debut and sexual behavior in Chinese women:Suggestions for optimal age of human papillomavirus vaccination in China

    PubMed Central

    Zhao, Fang-Hui; Tiggelaar, Sarah M.; Hu, Shang-Ying; Xu, Li-Na; Hong, Ying; Niyazi, Mayinuer; Gao, Xiao-Hong; Ju, Li-Rong; Zhang, Li-Qin; Feng, Xiang-Xian; Duan, Xian-Zhi; Song, Xiu-Ling; Wang, Jing; Yang, Yun; Li, Chang-Qing; Liu, Jia-Hua; Liu, Ji-Hong; Lu, Yu-Bo; Li, Li; Zhou, Qi; Liu, Jin-feng; Zhao, Na; Schmidt, Johannes E.; Qiao, You-Lin

    2017-01-01

    Objective Cervical cancer is the second most common cancer among women worldwide, and over 85% of cervical cancers occur in developing countries such as China. Lack of resources for nationwide cervical cancer screening in China makes vaccination against oncogenic strains of HPV particularly important. Knowledge of age at sexual debut and sexual behavior is essential prior to implementation of a national vaccination program. Methods and materials A cross-sectional epidemiologic survey was conducted across 21 urban and rural sites in China to assess age at sexual debut and sexual behavior. 98.6% of the 11,852 recruited women aged 15–59 years were included in the analysis. Data were collected using a short, nurse-administered questionnaire and analyzed using standard descriptive statistics and survival analysis. Results In urban areas, more than ten percent of the 15–19 year old age group were already sexually active at the time of interview; this number increased to nearly 44% in the 20–24 year old age group. Chinese young women with an occupation were more likely to be sexually active compared to female students of the same age, irrespective of area of residence. The crude median sexual debut age for the youngest age group was 17 years, earlier than the sexual debut age reported by older cohorts. Younger age cohorts had an earlier menarche age than older cohorts and were more likely to have more sexual partners than older women, and more likely to have partners with more than one female partner. Conclusion There is a trend towards earlier sexual debut and riskier sexual behaviors in younger age groups of Chinese women. These findings suggest that HPV vaccination of women between the ages of 13 and 15 years, before the completion of national compulsory education, is likely to contribute to the prevention of HPV infection and cervical cancer in China. PMID:22377277

  16. Strain, Negative Emotions, and Level of Criminality Among Chinese Incarcerated Women.

    PubMed

    Sun, Ivan Y; Luo, Haishan; Wu, Yuning; Lin, Wen-Hsu

    2016-05-01

    General strain theory (GST) has been one of the most frequently tested criminological theories. According to GST, strain tends to generate negative emotions, which create pressures for corrective action, such as crime and delinquency. Although GST has received strong empirical support, one under-addressed issue is the lack of diversity in sampling population in assessing the generalizability of the theory. Using survey data collected from 335 incarcerated women in four Chinese prisons, this study examined the impact of strain and negative emotions on the level of female criminality. The strain variable, physical abuse, and discrimination, exerted a positive effect on female inmates' levels of criminality, whereas negative emotions were not significantly related to female criminality. Two control variables, age of current offense and educational attainment, were predictive of female criminality, with younger and less-educated women having more serious criminality. Implications for future research and policy are discussed. © The Author(s) 2015.

  17. Efficacy of Fostera PRRS modified live virus vaccine against a Canadian heterologous virulent field strain of porcine reproductive and respiratory syndrome virus

    PubMed Central

    Savard, Christian; Alvarez, Fernando; Provost, Chantale; Chorfi, Younes; D’Allaire, Sylvie; Benoit-Biancamano, Marie-Odile; Gagnon, Carl A.

    2016-01-01

    Vaccination is a useful option to control infection with porcine reproductive and respiratory syndrome virus (PRRSV), and several modified live-PRRSV vaccines have been developed. These vaccines have shown some efficacy in reducing the incidence and severity of clinical disease as well as the duration of viremia and virus shedding but have failed to provide sterilizing immunity. The efficacy of modified live-virus (MLV) vaccines is greater against a homologous strain compared with heterologous PRRSV strains. The objective of this study was to evaluate the efficacy of Fostera PRRS MLV vaccine in protecting against challenge with a heterologous field strain widely circulating in the swine herds of eastern Canada. Forty-six piglets were divided into 4 groups: nonvaccinated-nonchallenged; nonvaccinated-challenged; vaccinated-challenged; and vaccinated-nonchallenged. The animals were vaccinated at 23 d of age with Fostera PRRS and challenged 23 d later with a heterologous field strain of PRRSV (FMV12-1425619). Overall, the vaccine showed some beneficial effects in the challenged animals by reducing the severity of clinical signs and the viral load. A significant difference between nonvaccinated and vaccinated animals was detected for some parameters starting 11 to 13 d after challenge, which suggested that the cell-mediated immune response or other delayed responses could be more important than pre-existing PRRSV antibodies in vaccinated animals within the context of protection against heterologous strains. PMID:26732457

  18. Development and characterization of an infectious cDNA clone of the modified live virus vaccine strain of equine arteritis virus.

    PubMed

    Zhang, Jianqiang; Go, Yun Young; Huang, Chengjin M; Meade, Barry J; Lu, Zhengchun; Snijder, Eric J; Timoney, Peter J; Balasuriya, Udeni B R

    2012-08-01

    A stable full-length cDNA clone of the modified live virus (MLV) vaccine strain of equine arteritis virus (EAV) was developed. RNA transcripts generated from this plasmid (pEAVrMLV) were infectious upon transfection into mammalian cells, and the resultant recombinant virus (rMLV) had 100% nucleotide identity to the parental MLV vaccine strain of EAV. A single silent nucleotide substitution was introduced into the nucleocapsid gene (pEAVrMLVB), enabling the cloned vaccine virus (rMLVB) to be distinguished from parental MLV vaccine as well as other field and laboratory strains of EAV by using an allelic discrimination real-time reverse transcription (RT)-PCR assay. In vitro studies revealed that the cloned vaccine virus rMLVB and the parental MLV vaccine virus had identical growth kinetics and plaque morphologies in equine endothelial cells. In vivo studies confirmed that the cloned vaccine virus was very safe and induced high titers of neutralizing antibodies against EAV in experimentally immunized horses. When challenged with the heterologous EAV KY84 strain, the rMLVB vaccine virus protected immunized horses in regard to reducing the magnitude and duration of viremia and virus shedding but did not suppress the development of signs of EVA, although these were reduced in clinical severity. The vaccine clone pEAVrMLVB could be further manipulated to improve the vaccine efficacy as well as to develop a marker vaccine for serological differentiation of EAV naturally infected from vaccinated animals.

  19. Phylogenetic Comparison of Influenza Virus Isolates from Three Medical Centers in Tehran with the Vaccine Strains during 2008-2009.

    PubMed

    Mousavi, Seyedeh Fahime; Kheiri, Masoumeh Tavassoti; Hosseini, Seyed Masoud; Taghizadeh, Mojgan; Fotouhi, Fatemeh; Heydarchi, Behnaz; Bashar, Rouzbeh; Gomari, Hosna

    2011-09-01

    Influenza virus is a major infectious pathogen of the respiratory system causing a high degree of morbidity and mortality annually. The worldwide vaccines are decided and produced annually by World Health Organization and licensed companies based on the samples collected from all over the world. The aim of this study was to determine phylogenecity and heterogenecity of the circulating influenza isolates during 2008-2009 outbreaks in Tehran, compare them with the vaccine strains that were recommended by WHO for the same period. Nasopharyngeal swabs (n=142) were collected from patients with influenza and influenza-like illness. Typing and subtyping of the isolates were performed using multiplex RT-PCR and phylogenetic analysis was carried out for hemagglutinin genes of the isolates. Fifty out of 142 samples were positive for influenza A virus, and no influenza B virus was detected. Phylogenetic analyses revealed that the A/H1N1 isolates were related closely to A/Brisbane/59/2007, and the A/H3N2 isolates were close to A/Brisbane/10/2007 vaccine strains. The findings of the present study demonstrate that the A/H1N1 was the predominant subtype of human influenza virus among the patients studied in Tehran during 2008-2009 winter seasons. In addition, some amino acid variation was found in Tehran/2008/H1N1 isolates from the 2008-2009 vaccine strain, but the H3N2 isolates showed higher genetic resemblance to the vaccine strain.

  20. African horse sickness in The Gambia: circulation of a live-attenuated vaccine-derived strain.

    PubMed

    Oura, C A L; Ivens, P A S; Bachanek-Bankowska, K; Bin-Tarif, A; Jallow, D B; Sailleau, C; Maan, S; Mertens, P C; Batten, C A

    2012-03-01

    African horse sickness virus serotype 9 (AHSV-9) has been known for some time to be circulating amongst equids in West Africa without causing any clinical disease in indigenous horse populations. Whether this is due to local breeds of horses being resistant to disease or whether the AHSV-9 strains circulating are avirulent is currently unknown. This study shows that the majority (96%) of horses and donkeys sampled across The Gambia were seropositive for AHS, despite most being unvaccinated and having no previous history of showing clinical signs of AHS. Most young horses (<3 years) were seropositive with neutralizing antibodies specific to AHSV-9. Eight young equids (<3 years) were positive for AHSV-9 by serotype-specific RT-PCR and live AHSV-9 was isolated from two of these horses. Sequence analysis revealed the presence of an AHSV-9 strain showing 100% identity to Seg-2 of the AHSV-9 reference strain, indicating that the virus circulating in The Gambia was highly likely to have been derived from a live-attenuated AHSV-9 vaccine strain.

  1. Characterization of two recent Japanese field isolates of canine distemper virus and examination of the avirulent strain utility as an attenuated vaccine.

    PubMed

    Takenaka, Akiko; Yoneda, Misako; Seki, Takahiro; Uema, Masashi; Kooriyama, Takanori; Nishi, Toshiya; Fujita, Kentaro; Miura, Ryuichi; Tsukiyama-Kohara, Kyoko; Sato, Hiroki; Kai, Chieko

    2014-12-05

    Recently, several new strains of canine distemper virus (CDV) have been isolated in Japan. To investigate their pathogenesis in dogs, the Yanaka and Bunkyo-K strains were investigated by infecting dogs and determining clinical signs, amount of virus, and antibody responses. The Yanaka strain is avirulent and induced an antibody response. The Bunkyo-K strain induced typical CDV clinical signs in infected dogs and virulence was enhanced by brain passage. Molecular and phylogenetic analyses of H genes demonstrated the Bunkyo-K strains were of a different lineage from Asia-1 group including the Yanaka strain and Asia-2 group that contain recent Japanese isolates, which were recently identified as major prevalent strains worldwide but distinct from old vaccine strains. Based on these data, we tested the ability of the Yanaka strain for vaccination. Inoculation with the Yanaka strain efficiently induced CDV neutralizing antibodies with no clinical signs, and the protection effects against challenge with either old virulent strain or Bunkyo-K strain were equal or greater when compared with vaccination by an original vaccine strain. Thus, the Yanaka strain is a potential vaccine candidate against recent prevalent CDV strains.

  2. Measles incidence rate and a phylogenetic study of contemporary genotype H1 measles strains in China: is an improved measles vaccine needed?

    PubMed

    Shi, Jingwei; Zheng, Jingtong; Huang, Honglan; Hu, Yu; Bian, Jiang; Xu, Deqi; Li, Fan

    2011-12-01

    The incidence of measles in China has increased over the last decade. To evaluate the genetic variation of measles strains, 16 measles wild-type virus strains were isolated from 14 vaccinated cases and 2 nonvaccinated cases in Jilin Province during 2005-2006, and their nucleoprotein (N) and hemagglutinin (H) genes were amplified by RT-PCR. The amplified products were sequenced and compared with the Edmonston virus and the existing vaccine strains (Changchun-47 and Shanghai-191). The results showed that the variation rate between the vaccine and wild-type strains was 9.8-12.0% in the N gene and 5.9-6.9% in the H gene, respectively. In addition, cross-neutralization assays revealed that although sera obtained from infants following primary vaccination effectively neutralized vaccine strains, the capacity in neutralizing H1 wild-type measles virus isolates was decreased fourfold. Antigenic ratios testing revealed that the antigenic relatedness between wild-type measles viruses and existing vaccine strains was notably low. These data suggest that the increased incidence of measles in Jilin Province may be attributed to the antigenic drift between wild-type and vaccine strains. Our findings strengthen the recommendation of supplemental immunization with existing vaccines and also strongly suggest a need for developing new vaccines to better control measles virus outbreaks.

  3. HI responses induced by seasonal influenza vaccination are associated with clinical protection and with seroprotection against non-homologous strains.

    PubMed

    Luytjes, Willem; Enouf, Vincent; Schipper, Maarten; Gijzen, Karlijn; Liu, Wai Ming; van der Lubben, Mariken; Meijer, Adam; van der Werf, Sylvie; Soethout, Ernst C

    2012-07-27

    Vaccination against influenza induces homologous as well as cross-specific hemagglutination inhibiting (HI) responses. Induction of cross-specific HI responses may be essential when the influenza strain does not match the vaccine strain, or even to confer a basic immune response against a pandemic influenza virus. We carried out a clinical study to evaluate the immunological responses after seasonal vaccination in healthy adults 18-60 years of age, receiving the yearly voluntary vaccination during the influenza season 2006/2007. Vaccinees of different age groups were followed for laboratory confirmed influenza (LCI) and homologous HI responses as well as cross-specific HI responses against the seasonal H1N1 strain of 2008 and pandemic H1N1 virus of 2009 (H1N1pdm09) were determined. Homologous HI titers that are generally associated with protection (i.e. seroprotective HI titers ≥40) were found in more than 70% of vaccinees. In contrast, low HI titers before and after vaccination were significantly associated with seasonal LCI. Cross-specific HI titers ≥40 against drifted seasonal H1N1 were found in 69% of vaccinees. Cross-specific HI titers ≥40 against H1N1pdm09 were also significantly induced, especially in the youngest age group. More specifically, cross-specific HI titers ≥40 against H1N1pdm09 were inversely correlated with age. We did not find a correlation between the subtype of influenza which was circulating at the age of birth of the vaccinees and cross-specific HI response against H1N1pdm09. These data indicate that the HI titers before and after vaccination determine the vaccination efficacy. In addition, in healthy adults between 18 and 60 years of age, young adults appear to be best able to mount a cross-protective HI response against H1N1pdm09 or drifted seasonal influenza after seasonal vaccination.

  4. Vaccination with Recombinant Baculovirus Expressing Ranavirus Major Capsid Protein Induces Protective Immunity in Chinese Giant Salamander, Andrias davidianus.

    PubMed

    Zhou, Xiaoyuan; Zhang, Xinglang; Han, Yahui; Jia, Qiuhong; Gao, Hongwei

    2017-07-25

    The Chinese giant salamander iridovirus (CGSIV), belonging to the genus Ranavirus in the family Iridoviridae, is the causative agent of an emerging infectious disease causing high mortality of more than 90% and economic losses in Chinese giant salamanders in China. In this study, a recombinant baculovirus-based vaccine expressing the CGSIV major capsid protein (MCP) was developed and its protective immunity in Chinese giant salamanders was evaluated. The recombinant Autographacalifornica nucleopolyhedrosis virus (AcNPV), expressing CGSIV MCP, designated as AcNPV-MCP, was generated with the highest titers of 1 × 10⁸ plaque forming units/mL (PFU/mL) and confirmed by Western blot and indirect immunofluorescence (IIF) assays. Western blot analysis revealed that the expressed MCP reacted with mouse anti-MCP monoclonal antibodies at the band of about 53 kDa. The results of IIF indicated that the MCP was expressed in the infected Spodoptera frugiperda 9 (Sf9) cells with the recombinant baculovirus, and the Chinese giant salamander muscle cells also transduced with the AcNPV-MCP. Immunization with the recombinant baculovirus of AcNPV-MCP elicited robust specific humoral immune responses detected by ELISA and neutralization assays and potent cellular immune responses in Chinese giant salamanders. Importantly, the effective immunization conferred highly protective immunity for Chinese giant salamanders against CGSIV challenge and produced a relative percent of survival rate of 84%. Thus, the recombinant baculovirus expressing CGSIV MCP can induce significant immune responses involving both humoral and cell-mediated immunity in Chinese giant salamanders and might represent a potential baculovirus based vaccine candidate for Chinese giant salamanders against CGSIV.

  5. Engineering and Preclinical Evaluation of Attenuated Nontyphoidal Salmonella Strains Serving as Live Oral Vaccines and as Reagent Strains▿†

    PubMed Central

    Tennant, Sharon M.; Wang, Jin-Yuan; Galen, James E.; Simon, Raphael; Pasetti, Marcela F.; Gat, Orit; Levine, Myron M.

    2011-01-01

    While nontyphoidal Salmonella (NTS) has long been recognized as a cause of self-limited gastroenteritis, it is becoming increasingly evident that multiple-antibiotic-resistant strains are also emerging as important causes of invasive bacteremia and focal infections, resulting in hospitalizations and deaths. We have constructed attenuated Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis strains that can serve as live oral vaccines and as “reagent strains” for subunit vaccine production in a safe and economical manner. Prototype attenuated vaccine strains CVD 1921 and CVD 1941, derived from the invasive wild-type strains S. Typhimurium I77 and S. Enteritidis R11, respectively, were constructed by deleting guaBA, encoding guanine biosynthesis, and clpP, encoding a master protease regulator. The clpP mutation resulted in a hyperflagellation phenotype. An additional deletion in fliD yielded reagent strains CVD 1923 and CVD 1943, respectively, which export flagellin monomers. Oral 50% lethal dose (LD50) analyses showed that the NTS vaccine strains were all highly attenuated in mice. Oral immunization with CVD 1921 or CVD 1923 protected mice against lethal challenge with wild-type S. Typhimurium I77. Immunization with CVD 1941 but not CVD 1943 protected mice against lethal infection with S. Enteritidis R11. Immune responses induced by these strains included high levels of serum IgG anti-lipopolysaccharide (LPS) and anti-flagellum antibodies, with titers increasing progressively during the immunization schedule. Since S. Typhimurium and S. Enteritidis are the most common NTS serovars associated with invasive disease, these findings can pave the way for development of a highly effective, broad-spectrum vaccine against invasive NTS. PMID:21807911

  6. Deletion of Major Nonessential Genomic Regions in the Vaccinia Virus Lister Strain Enhances Attenuation without Altering Vaccine Efficacy in Mice▿

    PubMed Central

    Dimier, Julie; Ferrier-Rembert, Audrey; Pradeau-Aubreton, Karine; Hebben, Matthias; Spehner, Danièle; Favier, Anne-Laure; Gratier, Danielle; Garin, Daniel; Crance, Jean-Marc; Drillien, Robert

    2011-01-01

    The vaccinia virus (VACV) Lister strain was one of the vaccine strains that enabled smallpox eradication. Although the strain is most often harmless, there have been numerous incidents of mild to life-threatening accidents with this strain and others. In an attempt to further attenuate the Lister strain, we investigated the role of 5 genomic regions known to be deleted in the modified VACV Ankara (MVA) genome in virulence in immunodeficient mice, immunogenicity in immunocompetent mice, and vaccine efficacy in a cowpox virus challenge model. Lister mutants were constructed so as to delete each of the 5 regions or various combinations of these regions. All of the mutants replicated efficiently in tissue culture except region I mutants, which multiplied more poorly in human cells than the parental strain. Mutants with single deletions were not attenuated or only moderately so in athymic nude mice. Mutants with multiple deletions were more highly attenuated than those with single deletions. Deleting regions II, III, and V together resulted in total attenuation for nude mice and partial attenuation for SCID mice. In immunocompetent mice, the Lister deletion mutants induced VACV specific humoral responses equivalent to those of the parental strain but in some cases lower cell-mediated immune responses. All of the highly attenuated mutants protected mice from a severe cowpox virus challenge at low vaccine doses. The data suggest that several of the Lister mutants combining multiple deletions could be used in smallpox vaccination or as live virus vectors at doses equivalent to those used for the traditional vaccine while displaying increased safety. PMID:21367889

  7. Efficacy and transmissibility of Newcastle disease I-2 vaccine strain against a field isolate of virulent ND virus (JF820294.1) in village chicken.

    PubMed

    Habibi, Hassan; Nili, Hassan; Asasi, Kramat; Mosleh, Najmeh; Firouzi, Sobhan; Mohammadi, Mitra

    2015-01-01

    This study was conducted to assess efficacy of heat-stable I-2 vaccine against Newcastle diseases in vaccinated and vaccinated in contact birds group following challenge against virulent Newcastle disease (ND) virus in village chicken. Also, to assess whether birds that have been exposed to vaccine virus-shedding, birds were protected against mortality and clinical signs after infection with a virulent strain of the ND virus (NDV). One hundred fifty one-day-old native chickens were divided into seven groups (4 experimental groups of 30 birds/group and 3 control groups (unvaccinated unchallenged, challenged, and just vaccinated). Birds in experimental groups were vaccinated either via drinking water or as food carrier with thermostable I-2 vaccine and then challenged with virulent isolate of NDV (JF820294.1), and eight birds were added as in-contact birds to vaccinated groups. Following challenge, seven extra birds were added to each group as in contact with vaccinated and challenged birds. Survival rate, clinical signs, necropsy finding, and mean antibody titer were evaluated in different experimental and control groups. Birds vaccinated via drinking water showed 100% survival rate. However, birds vaccinated with food carrier vaccine showed less than 50% survival rate. Based on the results obtained from this study, it can be recommended that I-2 vaccination via drinking water can effectively prevent ND in village chicken, since I-2 strain has been able to transmit to non-vaccinated-sensitive birds more effectively than velogenic NDV.

  8. Efficacy of Dart or Booster Vaccination with Strain RB51 in Protecting Bison against Experimental Brucella abortus Challenge

    PubMed Central

    Johnson, C. S.

    2012-01-01

    This study characterized the efficacy of the Brucella abortus strain RB51 vaccine in bison when delivered by single intramuscular vaccination (hand RB51), by single pneumatic dart delivery (dart RB51), or as two vaccinations approximately 13 months apart (booster RB51) in comparison to control bison. All bison were challenged intraconjunctivally in midgestation with 107 CFU of B. abortus strain 2308 (S2308). Bison were necropsied and sampled within 72 h of abortion or delivery of a live calf. Compared to nonvaccinated bison, bison in the booster RB51 treatment had a reduced (P < 0.05) incidence of abortion, uterine infection, or infection in maternal tissues other than the mammary gland at necropsy. Bison in single-vaccination treatment groups (hand RB51 and dart RB51) did not differ (P > 0.05) from the control group in the incidence of abortion or recovery of S2308 from uterine, mammary, fetal, or maternal tissues at necropsy. Compared to nonvaccinated animals, all RB51 vaccination groups had reduced (P < 0.05) mean colonization or incidence of infection in at least 2 of 4 target tissues, with the booster RB51 group having reduced (P < 0.05) colonization and incidence of infection in all target tissues. Our data suggest that booster vaccination of bison with RB51 enhances protective immunity against Brucella challenge compared to single vaccination with RB51 by hand or by pneumatic dart. Our study also suggests that an initial vaccination of calves followed by booster vaccination as yearlings should be an effective strategy for brucellosis control in bison. PMID:22496493

  9. Efficacy of dart or booster vaccination with strain RB51 in protecting bison against experimental Brucella abortus challenge.

    PubMed

    Olsen, S C; Johnson, C S

    2012-06-01

    This study characterized the efficacy of the Brucella abortus strain RB51 vaccine in bison when delivered by single intramuscular vaccination (hand RB51), by single pneumatic dart delivery (dart RB51), or as two vaccinations approximately 13 months apart (booster RB51) in comparison to control bison. All bison were challenged intraconjunctivally in midgestation with 10(7) CFU of B. abortus strain 2308 (S2308). Bison were necropsied and sampled within 72 h of abortion or delivery of a live calf. Compared to nonvaccinated bison, bison in the booster RB51 treatment had a reduced (P < 0.05) incidence of abortion, uterine infection, or infection in maternal tissues other than the mammary gland at necropsy. Bison in single-vaccination treatment groups (hand RB51 and dart RB51) did not differ (P > 0.05) from the control group in the incidence of abortion or recovery of S2308 from uterine, mammary, fetal, or maternal tissues at necropsy. Compared to nonvaccinated animals, all RB51 vaccination groups had reduced (P < 0.05) mean colonization or incidence of infection in at least 2 of 4 target tissues, with the booster RB51 group having reduced (P < 0.05) colonization and incidence of infection in all target tissues. Our data suggest that booster vaccination of bison with RB51 enhances protective immunity against Brucella challenge compared to single vaccination with RB51 by hand or by pneumatic dart. Our study also suggests that an initial vaccination of calves followed by booster vaccination as yearlings should be an effective strategy for brucellosis control in bison.

  10. Isolation of an attenuated myxoma virus field strain that can confer protection against myxomatosis on contacts of vaccinates.

    PubMed

    Bárcena, J; Pagès-Manté, A; March, R; Morales, M; Ramírez, M A; Sánchez-Vizcaíno, J M; Torres, J M

    2000-01-01

    Twenty MV strains obtained from a survey of field strains currently circulating throughout Spain were analyzed for their virulence and horizontal spreading among rabbits by contact transmission. A virus strain with suitable characteristics to be used as a potential vaccine against myxomatosis in wild rabbit populations was selected. Following inoculation, the selected MV strain elicited high levels of MV specific antibodies and induced protection of rabbits against a virulent MV challenge. Furthermore, the attenuated MV was transmitted to 9 out of 16 uninoculated rabbits by contact, inducing protection against myxomatosis.

  11. Determination of efficacious vaccine seed strains for use against Egyptian H5N1 highly pathogenic avian influenza viruses through antigenic cartography and in vivo challenge studies

    USDA-ARS?s Scientific Manuscript database

    Since 2006, there have been reported outbreaks of H5N1 highly pathogenic avian influenza (HPAI) in vaccinated chickens in Africa and Asia. This study provides experimental data for selection of efficacious H5N1 vaccine seed strains against recently circulating strains of H5N1 HPAI viruses in Egypt....

  12. Decreased ethyl carbamate generation during Chinese rice wine fermentation by disruption of CAR1 in an industrial yeast strain.

    PubMed

    Wu, Dianhui; Li, Xiaomin; Shen, Chao; Lu, Jian; Chen, Jian; Xie, Guangfa

    2014-06-16

    Saccharomyces cerevisiae metabolizes arginine to ornithine and urea during wine fermentations. In the fermentation of Chinese rice wine, yeast strains of S. cerevisiae do not fully metabolize urea, which will be secreted into the spirits and spontaneously reacts with ethanol to form ethyl carbamate, a potential carcinogenic agent for humans. To block the pathway of urea production, we genetically engineered two haploid strains to reduce the arginase (encoded by CAR1) activity, which were isolated from a diploid industrial Chinese rice wine strain. Finally the engineered haploids with opposite mating type were mated back to diploid strains, obtaining a heterozygous deletion strain (CAR1/car1) and a homozygous defect strain (car1/car1). These strains were compared to the parental industrial yeast strain in Chinese rice wine fermentations and spirit production. The strain with the homozygous CAR1 deletion showed significant reductions of urea and EC in the final spirits in comparison to the parental strain, with the concentration reductions by 86.9% and 50.5% respectively. In addition, EC accumulation was in a much lower tempo during rice wine storage. Moreover, the growth behavior and fermentation characteristics of the engineered diploid strain were similar to the parental strain.

  13. Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur

    PubMed Central

    2011-01-01

    Background Bacille Calmette-Guerin (BCG) is currently the only available vaccine against tuberculosis (TB) and comprises a heterogeneous family of sub-strains with genotypic and phenotypic differences. The World Health Organization (WHO) affirms that the characterization of BCG sub-strains, both on genomic and proteomic levels, is crucial for a better comprehension of the vaccine. In addition, these studies can contribute in the development of a more efficient vaccine against TB. Here, we combine two-dimensional electrophoresis (2DE) and mass spectrometry to analyse the proteomic profile of culture filtrate proteins (CFPs) from M. bovis BCG Moreau, the Brazilian vaccine strain, comparing it to that of BCG Pasteur. CFPs are considered of great importance given their dominant immunogenicity and role in pathogenesis, being available for interaction with host cells since early infection. Results The 2DE proteomic map of M. bovis BCG Moreau CFPs in the pH range 3 - 8 allowed the identification of 158 spots corresponding to 101 different proteins, identified by MS/MS. Comparison to BCG Pasteur highlights the great similarity between these BCG strains. However, quantitative analysis shows a higher expression of immunogenic proteins such as Rv1860 (BCG1896, Apa), Rv1926c (BCG1965c, Mpb63) and Rv1886c (BCG1923c, Ag85B) in BCG Moreau when compared to BCG Pasteur, while some heat shock proteins, such as Rv0440 (BCG0479, GroEL2) and Rv0350 (BCG0389, DnaK), show the opposite pattern. Conclusions Here we report the detailed 2DE profile of CFPs from M. bovis BCG Moreau and its comparison to BCG Pasteur, identifying differences that may provide relevant information on vaccine efficacy. These findings contribute to the detailed characterization of the Brazilian vaccine strain against TB, revealing aspects that may lead to a better understanding of the factors leading to BCG's variable protective efficacy against TB. PMID:21507239

  14. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine.

    PubMed

    Sanders, Barbara P; de Los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G; Song, Yutong; Cooper, Gillian; Crawt, Laura E; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2016-03-01

    The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4-9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive

  15. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine

    PubMed Central

    Sanders, Barbara P.; de los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G.; Song, Yutong; Cooper, Gillian; Crawt, Laura E.; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H. H. V.; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2016-01-01

    The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4–9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive

  16. Vaccines

    MedlinePlus Videos and Cool Tools

    Vaccinations are injections of antigens into the body. Once the antigens enter the blood, they circulate along ... suppressor T cells stop the attack. After a vaccination, the body will have a memory of an ...

  17. The haematological profile of female bronze turkeys (Meleagris gallopavo) vaccinated with various commercial strains of Newcastle disease.

    PubMed

    Schmidt, Elizabeth M D S; Santos, Ivan F C; Paulillo, António C; Martins, Gislaine R V; Denadai, Janine; Lapela, Ivan M

    2014-08-25

    The effects of vaccination on avian blood parameters are poorly understood. The present study was designed to evaluate whether different strains (Ulster 2C, B1, live LaSota and inactivated LaSota) of Newcastle disease vaccines had an effect on the haematological profile of female turkeys. Seventy-five female turkeys were allocated to treatment groups according to vaccination strain. All the birds, except those in the control group, were vaccinated at 32 weeks of age and revaccinated at 40 and 48 weeks of age. Blood samples were obtained for haematological analyses and serum samples for the haemagglutination inhibition test. Haemoglobin concentration was significantly lower (p < 0.05) in vaccinated female turkeys than in the control birds 28 days after vaccination. Monocytes were significantly higher (p < 0.05) in 44-week-old female turkeys vaccinated with inactivated LaSota strain compared with the other groups. Turkeys vaccinated with the B1 strain showed significantly higher (p < 0.05) total white blood cell counts compared with the other groups vaccinated with various commercial strains of the Newcastle disease virus. In conclusion, female turkeys showed significant differences in haemoglobin concentrations, monocytes and white blood cell counts when vaccinated against Newcastle disease.

  18. Pandemic influenza A virus codon usage revisited: biases, adaptation and implications for vaccine strain development.

    PubMed

    Goñi, Natalia; Iriarte, Andrés; Comas, Victoria; Soñora, Martín; Moreno, Pilar; Moratorio, Gonzalo; Musto, Héctor; Cristina, Juan

    2012-11-08

    Influenza A virus (IAV) is a member of the family Orthomyxoviridae and contains eight segments of a single-stranded RNA genome with negative polarity. The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm) in Mexico and USA. Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution. A comprehensive study to investigate the effect of selection pressure imposed by the human host on the codon usage of an emerging, pandemic IAV strain and the trends in viral codon usage involved over the pandemic time period is much needed. We performed a comprehensive codon usage analysis of 310 IAV strains from the pandemic of 2009. Highly biased codon usage for Ala, Arg, Pro, Thr and Ser were found. Codon usage is strongly influenced by underlying biases in base composition. When correspondence analysis (COA) on relative synonymous codon usage (RSCU) is applied, the distribution of IAV ORFs in the plane defined by the first two major dimensional factors showed that different strains are located at different places, suggesting that IAV codon usage also reflects an evolutionary process. A general association between codon usage bias, base composition and poor adaptation of the virus to the respective host tRNA pool, suggests that mutational pressure is the main force shaping H1N1 pdm IAV codon usage. A dynamic process is observed in the variation of codon usage of the strains enrolled in these studies. These results suggest a balance of mutational bias and natural selection, which allow the virus to explore and re-adapt its codon usage to different environments. Recoding of IAV taking into account codon bias, base composition and adaptation to host tRNA may provide important clues to develop new and appropriate vaccines.

  19. Immunogenic glycoproteins of laboratory and vaccine strains of Varicella-Zoster virus.

    PubMed Central

    Grose, C; Edmond, B J; Friedrichs, W E

    1981-01-01

    High-titered antisera were prepared in guinea pigs and rabbits against two strains of varicella-zoster virus (VZV): VZV-32, a low-passage laboratory strain, and VZV-Oka, a vaccine strain attenuated by passage in both human and guinea pig embryo cells. When the animal VZV-immune sera, as well as a human zoster serum, were used to precipitate radiolabeled glycoproteins from VZV-infected cells and the immune precipitates were analyzed by polyacrylamide gel electrophoresis and fluorography, it was observed that cell cultures infected with either strain had similar electrophoretic profiles containing major glycoproteins of approximate molecular weights 62,000, 98,000, and 118,000. A prominent high-molecular-weight (approximately 150,000) nonglycosylated polypeptide was identified in both strains also. These determinants were demonstrable by both indirect (staphylococcal protein A-antibody adsorbent) and direct immunoprecipitation, as long as VZV-immune sera with an antibody titer greater than or equal to 1:128 were used. Further analysis of individual caviid VZV antisera demonstrated some heterogeneity which appeared to be related to the method of immunization rather than the level of virus-specific antibody. VZV extracts emulsified with complete Freund adjuvant elicited an antibody response to all major immunogenic viral glycoproteins, whereas guinea pigs inoculated with virus alone during the primary immunization initially produced VZV antibody which failed to precipitate the highest-molecular-weight glycoprotein (gp118). Thus, Freund-type adjuvants promoted the maturation of the humoral immune response after VZV immunization in outbred guinea pigs. Images PMID:6262245

  20. Pandemic influenza A virus codon usage revisited: biases, adaptation and implications for vaccine strain development

    PubMed Central

    2012-01-01

    Background Influenza A virus (IAV) is a member of the family Orthomyxoviridae and contains eight segments of a single-stranded RNA genome with negative polarity. The first influenza pandemic of this century was declared in April of 2009, with the emergence of a novel H1N1 IAV strain (H1N1pdm) in Mexico and USA. Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution. A comprehensive study to investigate the effect of selection pressure imposed by the human host on the codon usage of an emerging, pandemic IAV strain and the trends in viral codon usage involved over the pandemic time period is much needed. Results We performed a comprehensive codon usage analysis of 310 IAV strains from the pandemic of 2009. Highly biased codon usage for Ala, Arg, Pro, Thr and Ser were found. Codon usage is strongly influenced by underlying biases in base composition. When correspondence analysis (COA) on relative synonymous codon usage (RSCU) is applied, the distribution of IAV ORFs in the plane defined by the first two major dimensional factors showed that different strains are located at different places, suggesting that IAV codon usage also reflects an evolutionary process. Conclusions A general association between codon usage bias, base composition and poor adaptation of the virus to the respective host tRNA pool, suggests that mutational pressure is the main force shaping H1N1 pdm IAV codon usage. A dynamic process is observed in the variation of codon usage of the strains enrolled in these studies. These results suggest a balance of mutational bias and natural selection, which allow the virus to explore and re-adapt its codon usage to different environments. Recoding of IAV taking into account codon bias, base composition and adaptation to host tRNA may provide important clues to develop new and appropriate vaccines. PMID:23134595

  1. Genetic analysis of attenuation markers of cold-adapted X-31 influenza live vaccine donor strain.

    PubMed

    Jang, Yo Han; Jung, Eun-Ju; Lee, Kwang-Hee; Byun, Young Ho; Yang, Seung Won; Seong, Baik Lin

    2016-03-08

    Cold-adapted live attenuated influenza vaccines (CAIVs) have been considered as a safe prophylactic measure to prevent influenza virus infections. The safety of a CAIV depends largely on genetic markers that confer specific attenuation phenotypes. Previous studies with other CAIVs reported that polymerase genes were primarily responsible for the attenuation. Here, we analyzed the genetic mutations and their phenotypic contribution in the X-31 ca strain, a recently developed alternative CAIV donor strain. During the cold-adaptation of its parental X-31 virus, various numbers of sequence changes were accumulated in all six internal genes. Phenotypic analysis with single-gene and multiple-gene reassortant viruses suggests that NP gene makes the largest contribution to the cold-adapted (ca) and temperature-sensitive (ts) characters, while the remaining other internal genes also impart attenuation characters with varying degrees. A balanced contribution of all internal genes to the attenuation suggests that X-31 ca could serve as an ideal master donor strain for CAIVs preventing influenza epidemics and pandemics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process.

    PubMed

    van de Waterbeemd, Bas; Streefland, Mathieu; van der Ley, Peter; Zomer, Bert; van Dijken, Harry; Martens, Dirk; Wijffels, René; van der Pol, Leo

    2010-07-05

    The use of detergent-extracted outer membrane vesicles (OMVs) is an established approach for development of a multivalent PorA vaccine against N. meningitidis serogroup B. Selective removal of lipopolysaccharide (LPS) decreases toxicity, but promotes aggregation and narrows the immune response. Detergent-free OMV vaccines retain all LPS, which preserves the native vesicle structure, but result in high toxicity and lower yield. The present study assessed the effects of gene mutations that attenuated LPS toxicity (lpxL1) or improved OMV yield (rmpM) in combination with the available OMV purification processes. The results substantiate that OMVs from a strain with both mutations, produced with a detergent-free process provide better vaccine characteristics than the traditional detergent-based approach. With comparable toxicity and yield, no aggregation and cross-protection against other PorA subtypes, these OMV vaccines are potentially safe and effective for parenteral use in humans. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. Stable Salmonella live vaccine strains with two or more attenuating mutations and any desired level of attenuation.

    PubMed

    Linde, K; Beer, J; Bondarenko, V

    1990-06-01

    Mutants optimally attenuated for highly susceptible hosts and protecting after a single oral vaccination are often overattenuated for host species being less susceptible. Therefore, to select vaccine strains optimally attenuated for the particular host species it is essential that a range of mutants with graded levels of attenuation be provided so as to permit lesser susceptibility to be compensated for by a correspondingly lower level of attenuation. This, while guaranteeing the stability through two-marker or multi-marker attenuation, can be suitably accomplished by slightly to moderately virulence-reducing mutations. Aspartic acid auxotrophy and, in particular, 'metabolic drift' mutations, possibly by additionally incorporating antiepidemic markers, are adopted for the mouse model to demonstrate stepwise production of S. typhimurium and S. typhi vaccine candidate strains with graded attenuation or any level of attenuation desirable. It is emphasized that this basic approach is relevant to practice.

  4. Live attenuated measles and mumps viral strain-containing vaccines and hearing loss: Vaccine Adverse Event Reporting System (VAERS), United States, 1990--2003.

    PubMed

    Asatryan, Armenak; Pool, Vitali; Chen, Robert T; Kohl, Katrin S; Davis, Robert L; Iskander, John K

    2008-02-26

    Hearing loss (HL) is a known complication of wild measles and mumps viral infections. As vaccines against measles and mumps contain live attenuated viral strains, it is biologically plausible that in some individuals HL could develop as a complication of vaccination against measles and/or mumps. Our objectives for this study were: to find and describe all cases of HL reported in the scientific literature and to the US Vaccine Adverse Events Reporting System (VAERS) for the period 1990--2003; and to determine reporting rate of HL after live attenuated measles and/or mumps viral strain-containing vaccines (MMCV) administration. We searched published reports for cases of HL identified after vaccination with MMCV. We also searched for reports of HL after MMCV administration submitted to VAERS from 1990 through 2003 and determined the dose-adjusted reporting rate of HL. Our main outcome measure was reported cases of HL after immunization with MMCV which were classified as idiopathic. We found 11 published case reports of HL following MMCV. The review of the VAERS reports identified 44 cases of likely idiopathic sensorineural HL after MMCV administration. The onset of HL in the majority of VAERS and published cases was consistent with the incubation periods of wild measles and mumps viruses. Based on the annual usage of measles-mumps-rubella (MMR) vaccine, we estimated the reporting rate of HL to be 1 case per 6-8 million doses. Thus, HL following MMCV has been reported in the literature and to the VAERS. Further studies are needed to better understand if there is a causal relationship between MMCV and HL.

  5. Genomics sequence analysis of the United States infectious laryngotracheitis vaccine strains chicken embryo origin (CEO) and tissue culture origin (TCO)

    USDA-ARS?s Scientific Manuscript database

    The genomic sequences of low and high passages of the United States infectious laryngotracheitis (ILT) vaccine strains CEO and TCO were determined using hybrid next generation sequencing in order to define genomic changes associated with attenuation and reversion to virulence. Phylogenetic analysis ...

  6. Comparison of microarray-predicted closest genomes to sequencing for poliovirus vaccine strain similarity and influenza A phylogeny.

    PubMed

    Maurer-Stroh, Sebastian; Lee, Charlie W H; Patel, Champa; Lucero, Marilla; Nohynek, Hanna; Sung, Wing-Kin; Murad, Chrysanti; Ma, Jianmin; Hibberd, Martin L; Wong, Christopher W; Simões, Eric A F

    2016-03-01

    We evaluate sequence data from the PathChip high-density hybridization array for epidemiological interpretation of detected pathogens. For influenza A, we derive similar relative outbreak clustering in phylogenetic trees from PathChip-derived compared to classical Sanger-derived sequences. For a positive polio detection, recent infection could be excluded based on vaccine strain similarity.

  7. A Brucella melitensis M5-90 wboA deletion strain is attenuated and enhances vaccine efficacy.

    PubMed

    Li, Zhi-Qiang; Shi, Jing-Xue; Fu, Wen-Dong; Zhang, Yu; Zhang, Jing; Wang, Zhen; Li, Tian-Sen; Chen, Chuang-Fu; Guo, Fei; Zhang, Hui

    2015-08-01

    Brucella spp. are Gram-negative intracellular pathogens of both humans and animals that cause great economic burdens in developing countries. Live attenuated vaccines are the most efficient means for the prevention and control of animal Brucellosis. However, Brucella vaccines (strain M5-90 and others) have several drawbacks and do not allow serological differentiation between vaccinated and infected animals. A wboA mutant was derived from Brucella melitensis (B. melitensis) vaccine strain M5-90 and tested for virulence and protective efficiency. T-cell responses (CD4(+), CD8(+)), levels of immunoglobulin G (IgG), and cytokine production were observed. WboA was also assessed as a diagnostic marker for Brucellosis. B. melitensis strain M5-90ΔwboA exhibited reduced survival in murine macrophages (RAW 264.7) and BALB/c mice and induced protective immunity in mice comparable to that from the parental strain M5-90. In mice, the wboA mutant elicited an anti-Brucella-specific IgG response and induced the secretion of gamma interferon (IFN-γ) and interleukin-2 (IL-2). In sheep, M5-90ΔwboA immunization induced the secretion of IFN-γ, and serum samples from sheep inoculated with M5-90ΔwboA were negative by Bengal Plate Test (RBPT) and Standard Tube Agglutination Test (STAT). In mice, probes against WboA antigen allowed for serological differentiation between natural infection and vaccination. The M5-90ΔwboA mutant is a potential attenuated live vaccine candidate against virulent B. melitensis 16M infection. It will be further evaluated in livestock.

  8. Isolation, Colonization, and Chlorpyrifos Degradation Mediation of the Endophytic Bacterium Sphingomonas Strain HJY in Chinese Chives (Allium tuberosum).

    PubMed

    Feng, Fayun; Ge, Jing; Li, Yisong; Cheng, Jinjin; Zhong, Jianfeng; Yu, Xiangyang

    2017-02-15

    The endophyte-plant interaction can benefit the host in many different ways. An endophytic bacterium strain (HJY) capable of degrading chlorpyrifos (CP) was isolated from Chinese chives (Allium tuberosum Rottl. ex Spreng). The isolated bacterium HJY classified as Sphingomonas sp. strain HJY could use CP as the sole carbon source. After being marked with the gfp gene, the colonization and distribution of strain HJY-gfp were directly observed in different tissues of Chinese chives with a confocal laser scanning microscope. The inoculation of strain HJY-gfp in Chinese chives resulted in a higher degradation of CP inside the plants than in uninoculated plants. With drench application, up to 70 and 66% of CP were removed from shoots and roots of inoculated Chinese chives, respectively. Moreover, up to 75% of CP was removed from the soil containing plants inoculated with HJY-gfp. With foliage application, the applied concentration of chlorpyrifos affected the degradation performance of strain HJY in Chinese chives. Significant differences were observed only between inoculated and uninoculated Chinese chives with the low applied concentration of CP. Together, other than natural endophyte-assisted plant protection for food safety, the interaction of HJY and plant may be also a promising strategy for in situ bioremediation of soil contaminated with CP.

  9. A live attenuated strain of Yersinia pestis KIM as a vaccine against plague.

    PubMed

    Sun, Wei; Six, David; Kuang, Xiaoying; Roland, Kenneth L; Raetz, Christian R H; Curtiss, Roy

    2011-04-05

    Yersinia pestis, the causative agent of plague, is a potential weapon of bioterrorism. Y. pestis evades the innate immune system by synthesizing tetra-acylated lipid A with poor Toll-like receptor 4 (TLR4)-stimulating activity at 37°C, whereas hexa-acylated lipid A, a potent TLR4 agonist, is made at lower temperatures. Synthesis of Escherichia coli LpxL, which transfers the secondary laurate chain to the 2'-position of lipid A, in Y. pestis results in production of hexa-acylated lipid A at 37°C, leading to significant attenuation of virulence. Previously, we described a Y. pestis vaccine strain in which crp expression is under the control of the arabinose-regulated araC P(BAD) promoter, resulting in a 4-5 log reduction in virulence. To reduce the virulence of the crp promoter mutant further, we introduced E. coli lpxL into the Y. pestis chromosome. The χ10030(pCD1Ap) (ΔlpxP32::P(lpxL)lpxL ΔP(crp21)::TT araC P(BAD)crp) construct likewise produced hexa-acylated lipid A at 37°C and was significantly more attenuated than strains harboring each individual mutation. The LD(50) of the mutant in mice, when administered subcutaneously or intranasally was >10(7)-times and >10(4)-times greater than wild type, respectively. Mice immunized subcutaneously with a single dose of the mutant were completely protected against a subcutaneous challenge of 3.6×10(7) wild-type Y. pestis and significantly protected (80% survival) against a pulmonary challenge of 1.2×10(4) live cells. Intranasal immunization also provided significant protection against challenges by both routes. This mutant is an immunogenic, highly attenuated live Y. pestis construct that merits further development as a vaccine candidate. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Control of Salmonella Enteritidis and Salmonella Gallinarum in birds by using live vaccine candidate containing attenuated Salmonella Gallinarum mutant strain.

    PubMed

    Penha Filho, Rafael Antonio Casarin; de Paiva, Jacqueline Boldrin; da Silva, Mariana Dias; de Almeida, Adriana Maria; Berchieri, Angelo

    2010-04-01

    The ideal live vaccine to control Salmonella in commercial chicken flocks should engender protection against various strains. The purpose of the present study was to confirm the attenuation of a Salmonella Gallinarum (SG) mutant strain with deletion on genes cobS and cbiA, that are involved in the biosynthesis of cobalamin. Furthermore, evaluate its use as a live vaccine against Salmonella. For the evaluation of the vaccine efficacy, two experiments were conducted separately. Birds from a commercial brown line of chickens were used to perform challenge with SG wild type strain and birds from a commercial white line of chickens were used to perform challenge with Salmonella Enteritidis (SE) wild type strain. In both experiments, the birds were separated in three groups (A, B and C). Birds were orally vaccinated with the SG mutant as the following programme: group A, one dose at 5 days of age; group B, one dose at 5 days of age and a second dose at 25 days of age; and group C, birds were kept unvaccinated as controls. At 45 days of age, birds from all groups, including the control, were challenged orally by SG wild type (brown line) or SE wild type (white line). Lastly, another experiment was performed to evaluate the use of the SG mutant strain to prevent caecal colonization by SE wild type on 1-day-old broiler chicks. Mortality and systemic infection by SG wild type strain were assessed in brown chickens; faecal shedding and systemic infection by SE wild type were assessed in white chickens and caecal colonization was assessed in broiler chicks. Either vaccination with one or two doses of SG mutant, were capable to protect brown chickens against SG wild type. In the experiment with white chickens, only vaccination with two doses of SG mutant protected the birds against challenge with SE wild type. Although, SG mutant could not prevent caecal colonization in 1-day-old broiler chicks by the challenge strain SE wild type. Overall, the results indicated that SG mutant

  11. Risks associated with the use of live-attenuated vaccine poliovirus strains and the strategies for control and eradication of paralytic poliomyelitis.

    PubMed

    Pliaka, Vaia; Kyriakopoulou, Zaharoula; Markoulatos, Panayotis

    2012-05-01

    The Global Polio Eradication Initiative was launched in 1988 with the aim to eliminate paralytic poliomyelitis. Two effective vaccines are available: inactivated polio vaccine (IPV) and oral polio vaccine (OPV). Since 1964, OPV has been used instead of IPV in most countries due to several economic and biological advantages. However, in rare cases, the live-attenuated Sabin strains of OPV revert to neurovirulence and cause vaccine-associated paralytic poliomyelitis in vaccinees or lead to emergence of vaccine-derived poliovirus strains. Attenuating mutations and recombination events have been associated with the reversion of vaccine strains to neurovirulence. The substitution of OPV with an improved new-generation IPV and the availability of new specific drugs against polioviruses are considered as future strategies for outbreak control and the eradication of paralytic poliomyelitis worldwide.

  12. Complete Genome Analysis of Three Live Attenuated Rinderpest Virus Vaccine Strains Derived through Serial Passages in Different Culture Systems

    PubMed Central

    Jeoung, Hye-Young; Lee, Myoung-Heon; Yeh, Jung-Yong; Lim, Ji-Ae; Lim, Seong-in; Oem, Jae-Ku; Song, Jae-Young; Lee, Won-Ha; Park, Jong-Hwan

    2012-01-01

    The genomes of three South Korean Rinderpest virus vaccine strains (L72, LA77, and LA96) were analyzed in order to investigate their genetic variability. These three vaccine strains were all derived from the same virus strain origin (Fusan) through repeated passages in different culture systems. The full genome length of the three strains was 15,882 nucleotides, and the sequence similarity between the three South Korean RPV strains at the nucleotide level was 98.1 to 98.9%. The genetic distance between Nakamura III, L72, LA77, LA96, and LATC06 and the Kabete strain was greater than that between the Fusan and Kabete strains for the P, V, and C genes. The difference in pathogenicity among these strains might be due to the V gene, which has a positive (>1) selection ratio based on the analysis of synonymous (dS) and nonsynonymous (dN) substitution rates (dN/dS ratio [ω]). PMID:23118448

  13. Antigenic and immunogenic spectrum of foot-and-mouth disease vaccine strain O1 Campos against representative viruses of topotypes that circulated in Asia over the past decade.

    PubMed

    Galdo Novo, S; Malirat, V; Maradei, E D; Espinoza, A M; Smitsaart, E; Pedemonte, A R; Mattion, N; Bergmann, I E

    2017-04-25

    Identifying vaccine strains to control outbreaks of foot-and-mouth disease virus that could spread to new regions is essential for contingency plans. This is the first report on the antigenic/immunogenic relationships of the South American O1/Campos vaccine strain with representative isolates of the three currently active Asian type O topotypes. Virus neutralization tests using O1/Campos post-vaccination sera derived from cattle and pigs predicted for both species acceptable cross-protection, even after single vaccination, established by r1 values and by expectancy of protection using monovalent or polyvalent vaccines. The results indicate that effective oil vaccines containing the O1/Campos strain can be used against Asian isolates, expanding the scope of O1/Campos strain included in vaccine banks to control emergencies caused by Asian viruses, even on single-dose vaccination, and to cover the need of effective vaccines in Asia during systematic vaccination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Focus Group Study of Chinese International Students' Knowledge and Beliefs About HPV Vaccination, Before and After Reading an Informational Pamphlet About Gardasil(®).

    PubMed

    Gao, Haijuan; Okoror, Titilayo A; Hyner, Gerald C

    2016-10-01

    An increasing need for Human Papillomavirus (HPV) vaccines in China remains unmet in the mainland and the knowledge and intentions of Chinese youth regarding vaccination is unknown. In the fall of 2013, 44 Chinese international students (CIS) attending a university in the United States Midwest participated in 10 focus group discussions (five female and five male). Result showed that participants have limited awareness and knowledge about HPV infection and vaccination, participants erroneously believed that the causes of cervical cancer are abortion and miscarriage. Participants rely heavily on informal sources such as Chinese-based social media platforms and personal social networks for information on sexually transmitted infections. Sexual cultures and behaviors are perceived differently between CIS born in the 1990s and 1980s. Interestingly, participants' perceived stigma about HPV infection decreased with improving knowledge level during group discussions. In conclusion, HPV vaccine should be further promoted alongside sex education among CIS.

  15. Protection provided by a recombinant ALVAC(®)-WNV vaccine expressing the prM/E genes of a lineage 1 strain of WNV against a virulent challenge with a lineage 2 strain.

    PubMed

    Minke, J M; Siger, L; Cupillard, L; Powers, B; Bakonyi, T; Boyum, S; Nowotny, N; Bowen, R

    2011-06-20

    The emergence of lineage 2 strains of WNV in Europe as a cause of clinical disease and mortality in horses raised the question whether the existing WNV vaccines, all based on lineage 1 strains, protect against circulating lineage 2 strains of WNV. In the present paper we have determined the level of cross protection provided by the recombinant ALVAC(®)-WNV vaccine in a severe challenge model that produces clinical signs of WNV type 2 disease. Ten horses were vaccinated twice at 4 weeks interval with one dose of the ALVAC-WNV vaccine formulated at the minimum protective dose. A further 10 horses served as controls. Two weeks after the second vaccination, all horses were challenged intrathecally with a recent neurovirulent lineage 2 strain of WNV. The challenge produced viraemia in 10 out of 10 and encephalitis in 9 out of 10 control horses. Three horses had to be euthanized for humane reasons. In contrast, none of the vaccinated horses developed WNV disease and only 1 vaccinated horse became viraemic at a single time point at low titre. The prevalence of WNV disease and viraemia were significantly lower in the vaccinated horses than in the control horses (P<0.0001 for both). Based on these results, the ALVAC-WNV vaccine will provide veterinarians with an effective tool to control infections caused by lineage 1 and 2 strains of WNV.

  16. Recombinant measles AIK-C vaccine strain expressing heterologous virus antigens.

    PubMed

    Nakayama, Tetsuo; Sawada, Akihito; Yamaji, Yoshiaki; Ito, Takashi

    2016-01-04

    Further attenuated measles vaccines were developed more than 50 years ago and have been used throughout the world. Recombinant measles vaccine candidates have been developed and express several heterologous virus protective antigens. Immunogenicity and protective actions were confirmed using experimental animals: transgenic mice, cotton rats, and primates. The recent development of measles vaccine-based vectored vaccine candidates has been reviewed and some information on recombinant measles vaccines expressing respiratory syncytial virus proteins has been shown and discussed.

  17. [An assessment of the immunoepidemiological efficacy of a liquid cultured killed vaccine against tick-borne encephalitis virus strain 205 in the Maritime Territory].

    PubMed

    Leonova, G N; Liubimova, N B; Sergeev, G A; Muratkina, S M; Krugliak, S P; Bobkov, A V; Bondarenko, S I; Tutubalina, G N; Beliaev, M M

    1992-02-01

    Inactivated vaccine against tick-borne encephalitis (TBE), prepared on the basis of strain 205, is characterized by epidemiological (53%) and immunobiological activity. The appearance of a few TBE cases among the vaccinees is probably due to different maturation rate of immune response to various strains (different specificity of immune response). A suggestion has been made that no inactivated vaccine prepared from a single strain can produce a reliable protective effect because of pronounced heterogeneity of the population of TBE virus.

  18. Challenge of Pigs with Classical Swine Fever Viruses after C-Strain Vaccination Reveals Remarkably Rapid Protection and Insights into Early Immunity

    PubMed Central

    Haines, Felicity J.; Johns, Helen L.; Sosan, Olubukola A.; Salguero, Francisco J.; Clifford, Derek J.; Steinbach, Falko; Drew, Trevor W.; Crooke, Helen R.

    2012-01-01

    Pre-emptive culling is becoming increasingly questioned as a means of controlling animal diseases, including classical swine fever (CSF). This has prompted discussions on the use of emergency vaccination to control future CSF outbreaks in domestic pigs. Despite a long history of safe use in endemic areas, there is a paucity of data on aspects important to emergency strategies, such as how rapidly CSFV vaccines would protect against transmission, and if this protection is equivalent for all viral genotypes, including highly divergent genotype 3 strains. To evaluate these questions, pigs were vaccinated with the Riemser® C-strain vaccine at 1, 3 and 5 days prior to challenge with genotype 2.1 and 3.3 challenge strains. The vaccine provided equivalent protection against clinical disease caused by for the two challenge strains and, as expected, protection was complete at 5 days post-vaccination. Substantial protection was achieved after 3 days, which was sufficient to prevent transmission of the 3.3 strain to animals in direct contact. Even by one day post-vaccination approximately half the animals were partially protected, and were able to control the infection, indicating that a reduction of the infectious potential is achieved very rapidly after vaccination. There was a close temporal correlation between T cell IFN-γ responses and protection. Interestingly, compared to responses of animals challenged 5 days after vaccination, challenge of animals 3 or 1 days post-vaccination resulted in impaired vaccine-induced T cell responses. This, together with the failure to detect a T cell IFN-γ response in unprotected and unvaccinated animals, indicates that virulent CSFV can inhibit the potent antiviral host defences primed by C-strain in the early period post vaccination. PMID:22235283

  19. Oral re-vaccination of Eurasian wild boar with Mycobacterium bovis BCG yields a strong protective response against challenge with a field strain

    PubMed Central

    2014-01-01

    Background Field vaccination trials with Mycobacterium bovis BCG, an attenuated mutant of M. bovis, are ongoing in Spain, where the Eurasian wild boar (Sus scrofa) is regarded as the main driver of animal tuberculosis (TB). The oral baiting strategy consists in deploying vaccine baits twice each summer, in order to gain access to a high proportion of wild boar piglets. The aim of this study was to assess the response of wild boar to re-vaccination with BCG and to subsequent challenge with an M. bovis field strain. Results BCG re-vaccinated wild boar showed reductions of 75.8% in lesion score and 66.9% in culture score, as compared to unvaccinated controls. Only one of nine vaccinated wild boar had a culture-confirmed lung infection, as compared to seven of eight controls. Serum antibody levels were highly variable and did not differ significantly between BCG re-vaccinated wild boar and controls. Gamma IFN levels differed significantly between BCG re-vaccinated wild boar and controls. The mRNA levels for IL-1b, C3 and MUT were significantly higher in vaccinated wild boar when compared to controls after vaccination and decreased after mycobacterial challenge. Conclusions Oral re-vaccination of wild boar with BCG yields a strong protective response against challenge with a field strain. Moreover, re-vaccination of wild boar with BCG is not counterproductive. These findings are relevant given that re-vaccination is likely to happen under real (field) conditions. PMID:24766746

  20. Evaluation of probiotic properties of Lactobacillus plantarum strains isolated from Chinese sauerkraut.

    PubMed

    Yu, Zhihui; Zhang, Xue; Li, Shengyu; Li, Changying; Li, Da; Yang, Zhennai

    2013-03-01

    Lactobacillus plantarum strains isolated and identified from naturally-fermented Chinese sauerkraut were examined in vitro for potential probiotic properties and in vivo for cholesterol-lowering effect in mice. Among 7 isolated L. plantarum strains, strains S2-5 and S4-1 were found to possess desirable probiotic properties including ability to survive at pH 2.0 for 60 min, tolerate pancreatin and bile salts, adhere to Caco-2 cells, produce high β-galactosidase activity and antimicrobial activity against Escherichia coli O157 and Shigella flexneri CMCC(B). In addition, strains S2-5 and S4-1 were susceptible to several antibiotics, and capable of reducing cholesterol level in MRS medium by assimilation of cholesterol at 20.39 and 22.28 μg ml(-1), respectively. The in vivo study with L. plantarum S4-1 showed that feeding with fermented milk containing this strain was able to effectively reduce serum cholesterol level in mice, demonstrating its potential as an excellent probiotic candidate for applications in functional products.

  1. Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis

    PubMed Central

    Wang, Jingbo; Liu, Rui; Liu, Baoxiu; Yang, Yan; Xie, Jun; Zhu, Naishuo

    2017-01-01

    Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine. Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug. Pathway enrichment analysis found that the targets participated in several immunological processes. Based on this, we selected cordycepin as a target compound to serve as an adjuvant of the hepatitis B vaccine because the existing vaccine often fails to induce an effective immune response in many subjects. Animal and cellular experiments finally validated that the new vaccine simultaneously improves the humoral and cellular immunity of BALB/c mice without side effects. All this results demonstrate that cordycepin could work as adjuvant to hepatitis b vaccine and systems-pharmacology analysis could be used as a new method to select adjuvants. PMID:28317886

  2. Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis.

    PubMed

    Wang, Jingbo; Liu, Rui; Liu, Baoxiu; Yang, Yan; Xie, Jun; Zhu, Naishuo

    2017-03-20

    Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine. Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug. Pathway enrichment analysis found that the targets participated in several immunological processes. Based on this, we selected cordycepin as a target compound to serve as an adjuvant of the hepatitis B vaccine because the existing vaccine often fails to induce an effective immune response in many subjects. Animal and cellular experiments finally validated that the new vaccine simultaneously improves the humoral and cellular immunity of BALB/c mice without side effects. All this results demonstrate that cordycepin could work as adjuvant to hepatitis b vaccine and systems-pharmacology analysis could be used as a new method to select adjuvants.

  3. Genome-Wide Evolutionary Analyses of G1P[8] Strains Isolated Before and After Rotavirus Vaccine Introduction.

    PubMed

    Zeller, Mark; Donato, Celeste; Trovão, Nídia Sequeira; Cowley, Daniel; Heylen, Elisabeth; Donker, Nicole C; McAllen, John K; Akopov, Asmik; Kirkness, Ewen F; Lemey, Philippe; Van Ranst, Marc; Matthijnssens, Jelle; Kirkwood, Carl D

    2015-08-08

    Rotaviruses are the most important etiological agent of acute gastroenteritis in young children worldwide. Among the first countries to introduce rotavirus vaccines into their national immunization programs were Belgium (November 2006) and Australia (July 2007). Surveillance programs in Belgium (since 1999) and Australia (since 1989) offer the opportunity to perform a detailed comparison of rotavirus strains circulating pre- and postvaccine introduction. G1P[8] rotaviruses are the most prominent genotype in humans, and a total of 157 G1P[8] rotaviruses isolated between 1999 and 2011 were selected from Belgium and Australia and their complete genomes were sequenced. Phylogenetic analysis showed evidence of frequent reassortment among Belgian and Australian G1P[8] rotaviruses. Although many different phylogenetic subclusters were present before and after vaccine introduction, some unique clusters were only identified after vaccine introduction, which could be due to natural fluctuation or the first signs of vaccine-driven evolution. The times to the most recent common ancestors for the Belgian and Australian G1P[8] rotaviruses ranged from 1846 to 1955 depending on the gene segment, with VP7 and NSP4 resulting in the most recent estimates. We found no evidence that rotavirus population size was affected after vaccine introduction and only six amino acid sites in VP2, VP3, VP7, and NSP1 were identified to be under positive selective pressure. Continued surveillance of G1P[8] strains is needed to determine long-term effects of vaccine introductions, particularly now rotavirus vaccines are implemented in the national immunization programs of an increasing number of countries worldwide.

  4. Brucella abortus S19 and RB51 vaccine immunogenicity test: Evaluation of three mice (BALB/c, Swiss and CD-1) and two challenge strains (544 and 2308).

    PubMed

    Miranda, Karina Leite; Dorneles, Elaine Maria Seles; Pauletti, Rebeca Barbosa; Poester, Fernando Padilla; Lage, Andrey Pereira

    2015-01-15

    The aim of the present study was to evaluate the use of different mouse strains (BALB/c, Swiss and CD-1) and different challenge strains (Brucella abortus 544 and 2308) in the study of B. abortus vaccine (S19 and RB51) immunogenicity test in the murine model. No significant difference in B. abortus vaccine potency assay was found with the use of B. abortus 544 or B. abortus 2308 as challenge strain. Results of variance analysis showed an interaction between treatment and mouse strain; therefore these parameters could not be compared separately. When CD-1 groups were compared, those vaccinated showed significantly lower counts than non-vaccinated ones (P<0.05), independently of the vaccine received (S19 or RB51). Similar results were observed on BALB/c groups. However, in Swiss mouse groups, S19 was more protective than RB51 (P<0.05), which showed protection when compared to the non-vaccinated group (P<0.05). In summary, data from the present study showed that CD-1, BALB/c and Swiss mice strains, as well as both challenge strains, B. abortus strains 544 and 2308, can be used in immunogenicity tests of S19 and RB51 vaccines.

  5. Comparative evaluation of two vaccine candidates against experimental leishmaniasis due to Leishmania major infection in four inbred mouse strains.

    PubMed

    Benhnini, Fouad; Chenik, Mehdi; Laouini, Dhafer; Louzir, Hechmi; Cazenave, Pierre André; Dellagi, Koussay

    2009-11-01

    Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders that also support the development of experimental leishmaniasis due to L. major. In this study, we sought to determine whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins, namely, LACK (for Leishmania homolog of receptor for activated C kinase) and LmPDI (for L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c, and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in outbred human populations and should be selected for clinical trials.

  6. Efficacy evaluation of the C-strain-based vaccines against the subgenotype 2.1d classical swine fever virus emerging in China.

    PubMed

    Luo, Yuzi; Ji, Shengwei; Lei, Jian-Lin; Xiang, Guang-Tao; Liu, Yan; Gao, Yao; Meng, Xing-Yu; Zheng, Guanglai; Zhang, En-Yu; Wang, Yimin; Du, Ming-Liang; Li, Yongfeng; Li, Su; He, Xi-Jun; Sun, Yuan; Qiu, Hua-Ji

    2017-03-01

    Classical swine fever (CSF) is a devastating infectious disease of pigs caused by classical swine fever virus (CSFV). The disease has been controlled following extensive vaccination with the lapinized attenuated vaccine C-strain for decades in China. However, frequent CSF outbreaks occurred recently in a large number of C-strain-vaccinated pig farms in China and a new subgenotype 2.1d of CSFV has been reported to be responsible for the outbreaks. Here we analyzed the molecular variations and antigenic differences among the C-strain-based commercial vaccines of different origins from different manufacturers in China, and reevaluated the vaccines against the emerging subgenotype 2.1d strain of CSFV. The results showed that the C-strain adapted to the continuous ST cell line (CST) contain a unique M290K variation on the E2 protein, compared to those of primary BT cells (CBT) or rabbit origin (CRT) and the traditional C-strain sequences available in the GenBank database. Serum neutralization test revealed the antigenic differences between CST and CBT or CRT. Notably, the neutralizing titers of porcine anti-C-strain sera against the CSFV isolate of subgenotype 2.1d were significantly lower than those against C-strain or Shimen strain. The C-strain-vaccinated, subgenotype 2.1d HLJZZ2014 strain-challenged pigs did not show any clinical signs and all survived. However, these pigs displayed mild pathological and histological lesions, and the CSFV viral RNA was detected in the various tissue and blood samples. Taken together, the C-strain-based vaccines of different origins showed molecular variations and antigenic differences, and could provide clinical but not pathological and virological protection against the subgenotype 2.1d CSFV emerging in China. Further investigation is needed to comprehensively assess the efficacy of C-strain of different doses against the subgenotype 2.1d CSFV.

  7. Live Vaccine Strain Francisella tularensis is Detectable at the Inoculation Site but Not in Blood after Vaccination Against Tularemia

    DTIC Science & Technology

    2006-08-10

    transmission have been observed. The vaccine is administered by scarification and forms a small lesion, mimicking a very mild case of ulcer- oglandular...plied to the skin surface with scarification , in a similar manner to the vaccinia (smallpox) vaccine, with subsequent develop- ment of cutaneous lesions...No previous study has made use of multiple diagnostic platforms to detect the presence of LVS F. tularensis at the scarification site or in the

  8. Differentiation between wild-type and vaccines strains of varicella zoster virus (VZV) based on four single nucleotide polymorphisms.

    PubMed

    Jin, L; Xu, S; Maple, P A C; Xu, W; Brown, K E

    2017-09-01

    Varicella-zoster virus (VZV) infection (chickenpox) results in latency and subsequent reactivation manifests as shingles. Effective attenuated vaccines (vOka) are available for prevention of both illnesses. In this study, an amplicon-based sequencing method capable of differentiating between VZV wild-type (wt) strains and vOka vaccine is described. A total of 44 vesicular fluid specimens collected from 43 patients (16 from China and 27 from the UK) with either chickenpox or shingles were investigated, of which 10 had received previous vaccination. Four sets of polymerase chain reactions were set up simultaneously with primers amplifying regions encompassing four single nucleotide polymorphisms (SNPs), '69349-106262-107252-108111'. Nucleotide sequences were generated by Sanger sequencing. All samples except one had a wt SNP profile of 'A-T-T-T'. The sample collected from a patient who received vaccine 7-10 days ago, along with VZV vaccine preparations, Zostavax and Baike-varicella gave a SNP profile 'G-C-C-C'. The results show that this method can distinguish vaccine-derived virus from wt viruses from main four clades, (clades 1-4) and should be of utility worldwide.

  9. Effect of monovalent rotavirus vaccine on rotavirus disease burden and circulating rotavirus strains among children in Morocco.

    PubMed

    Benhafid, Mohammed; Elomari, Nezha; Azzouzi Idrissi, Meryem; Rguig, Ahmed; Gentsch, Jon R; Parashar, Umesh; Elaouad, Rajae

    2015-06-01

    Rotarix(TM) vaccine was introduced into the National Program of Immunization of Morocco in October 2010, reaching quickly 87% of the target population of children nationally. The incidence of rotavirus gastroenteritis and the prevalence of circulating rotavirus strains has been monitored in three sentinel hospitals since June 2006. The average percentage of rotavirus positive cases among all children under 5 years old hospitalized for gastroenteritis during the pre-vaccine period (2006-2010) was 44%. This percentage dropped to 29%, 15% and 24% in the 3 years post vaccine introduction (2011, 2012 and 2013), which is a decline of 34%, 66%, and 45%, respectively. Declines in prevalence were greatest among children 0-1 years of age (53%) and were most prominent during the winter and autumn rotavirus season. The prevalence of the G2P[4] and G9P[8] genotype sharply increased in the post vaccine period (2011-2013) compared to the previous seasons (2006-2010). Rotavirus vaccines have reduced greatly the number of children hospitalized due to rotavirus infection at the three sentinel hospitals; it is however unclear if the predominance of G2P[4] and G9P[8] genotypes is related to the vaccine introduction, or if this is attributable to normal genotype fluctuations. Continued surveillance will be pivotal to answer this question in the future. © 2015 Wiley Periodicals, Inc.

  10. Persistence of cell-mediated immunity three decades after vaccination with the live vaccine strain of Francisella tularensis

    PubMed Central

    Eneslätt, Kjell; Rietz, Cecilia; Rydén, Patrik; Stöven, Svenja; House, Robert V.; Wolfraim, Lawrence A.; Tärnvik, Arne; Sjöstedt, Anders

    2012-01-01

    Summary The efficacy of many vaccines against intracellular bacteria depends on the generation of cell-mediated immunity, but studies to determine the duration of immunity are usually confounded by re-exposure. The causative agent of tularemia, Francisella tularensis, is rare in most areas and, therefore, tularemia vaccination is an interesting model for studies of the longevity of vaccine-induced cell-mediated immunity. Here lymphocyte proliferation and cytokine production in response to F. tularensis were assayed in two groups of 16 individuals, vaccinated 1-3 or 27-34 years previously. As compared to naïve individuals, vaccinees of both groups showed higher proliferative responses and, out of 17 cytokines assayed, higher levels of MIP-1β, IFN-γ, IL-10, and IL-5 in response to recall stimulation. The responses were very similar in the two groups of vaccinees. A statistical model was developed to predict the immune status of the individuals and by use of two parameters, proliferative responses and levels of IFN-γ, 91.1% of the individuals were correctly classified. Using flow cytometry analysis, we demonstrated that during recall stimulation, expression of IFN-γ by CD4+CCR7+, CD4+CD62L+, CD8+CCR7+, and CD8+CD62L+ cells significantly increased in samples from vaccinated donors. In conclusion, cell-mediated immunity was found to persist three decades after tularemia vaccination without evidence of decline. PMID:21442618

  11. Phylogenetic Comparison of Influenza Virus Isolates from Three Medical Centers in Tehran with the Vaccine Strains during 2008-2009

    PubMed Central

    Mousavi, Seyedeh Fahime; Kheiri, Masoumeh Tavassoti; Hosseini, Seyed Masoud; Taghizadeh, Mojgan; Fotouhi, Fatemeh; Heydarchi, Behnaz; Bashar, Rouzbeh; Gomari, Hosna

    2011-01-01

    Background: Influenza virus is a major infectious pathogen of the respiratory system causing a high degree of morbidity and mortality annually. The worldwide vaccines are decided and produced annually by World Health Organization and licensed companies based on the samples collected from all over the world. The aim of this study was to determine phylogenecity and heterogenecity of the circulating influenza isolates during 2008-2009 outbreaks in Tehran, compare them with the vaccine strains that were recommended by WHO for the same period. Methods: Nasopharyngeal swabs (n=142) were collected from patients with influenza and influenza-like illness. Typing and subtyping of the isolates were performed using multiplex RT-PCR and phylogenetic analysis was carried out for hemagglutinin genes of the isolates. Results: Fifty out of 142 samples were positive for influenza A virus, and no influenza B virus was detected. Phylogenetic analyses revealed that the A/H1N1 isolates were related closely to A/Brisbane/59/2007, and the A/H3N2 isolates were close to A/Brisbane/10/2007 vaccine strains. Conclusion: The findings of the present study demonstrate that the A/H1N1 was the predominant subtype of human influenza virus among the patients studied in Tehran during 2008-2009 winter seasons. In addition, some amino acid variation was found in Tehran/2008/H1N1 isolates from the 2008-2009 vaccine strain, but the H3N2 isolates showed higher genetic resemblance to the vaccine strain. PMID:23359291

  12. New Emerging Recombinant HIV-1 Strains and Close Transmission Linkage of HIV-1 Strains in the Chinese MSM Population Indicate a New Epidemic Risk

    PubMed Central

    Xu, Jianqing; Lei, Yanhua; Jin, Lin; Zhong, Ping; Han, Renzhi; Su, Bin

    2013-01-01

    In recent years, the population of men who have sex with men (MSM) have become the most significant increasing group of HIV-1 transmission in China. To identify new recombinant strains and transmission patterns of HIV-1 in Chinese MSM population, a cross-sectional investigation of MSM in Anhui Province (in south-eastern China) was performed in 2011. The diagnosed AIDS case rate, CD4 T-cell counts, HIV subtypes, and origin of the recombinant strains were investigated in 138 collected samples. The phylogenetic and bootscan analyses demonstrated that, apart from three previously reported circulating strains (CRF07_BC, CRF01_AE, subtype B), various recombinant strains among subtype B, subtype C, CRF01_AE, and CRF07_BC were simultaneously identified in Chinese MSM for the first time. The introducing time of B subtype in Chinese MSM populations was estimated in 1985, CRF01_AE in 2000, and CRF07_BC in 2003; the latter two account for more than 85% of MSM infections. Notably, in comparison with B subtype infections in Anhui MSM, CRF01_AE, with the highest prevalence rate, may accelerate AIDS progression. Over half of patients (56%) infected with new recombinant strains infection are diagnosed as progression into AIDS. Both Bayes and phylogenetic analyses indicated that there was active HIV transmission among MSM nationwide, which may facilitate the transmission of the new 01B recombinant strains in MSM. In conclusion, new recombinant strains and active transmission were identified in the Chinese MSM population, which may lead to a new alarming HIV pandemic in this population due to the increased pathogenesis of the newly emerging strains. PMID:23372706

  13. A modified live PRRSV vaccine and the pathogenic parent strain induce regulatory T cells in pigs naturally infected with Mycoplasma hyopneumoniae.

    PubMed

    LeRoith, T; Hammond, S; Todd, S M; Ni, Y; Cecere, T; Pelzer, K D

    2011-04-15

    The lack of heterologous protection by porcine reproductive and respiratory syndrome virus (PRRSV) vaccines is currently a major problem in the field. Heterologous protection by PRRS vaccines depends on the ability of the vaccine to induce an interferon gamma (IFN-γ) response. One mechanism by which the virus evades the immune system is by activating regulatory T cells (T(regs)), resulting in induction of interleukin 10 rather than IFN-γ. Our hypothesis that current PRRS vaccines do not differ from pathogenic strains in the ability to induce T(regs) was tested by inoculating three groups of pigs with two pathogenic viruses and an attenuated vaccine strain and evaluating the number of T(regs) in peripheral blood mononuclear cells. Before inoculation, the pigs, although vaccinated became infected naturally with Mycoplasma hyopneumoniae before shipment to our research facility. Our results show that the PRRSV vaccine strain and parent strain are equally able to induce T(regs) in pigs naturally infected with M. hyopneumoniae. Pigs in the vaccine and PRRSV groups had higher lung lesion scores than pigs in the control groups. The results suggest that the exacerbation M. hyopneumoniae respiratory disease may be due to the ability of PRRSV vaccination and viral infection to induce regulatory T cells.

  14. Protection by novel vaccine candidates, Mycobacterium tuberculosis ΔmosR and ΔechA7, against challenge with a Mycobacterium tuberculosis Beijing strain.

    PubMed

    Marcus, Sarah A; Steinberg, Howard; Talaat, Adel M

    2015-10-13

    Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), infects over two billion people, claiming around 1.5 million lives annually. The only vaccine approved for clinical use against this disease is the Bacillus Calmette-Guérin (BCG) vaccine. Unfortunately, BCG has limited efficacy against the adult, pulmonary form of tuberculosis. This vaccine was developed from M. bovis with antigen expression and host specificity that differ from M. tuberculosis. To address these problems, we have designed two novel, live attenuated vaccine (LAV) candidates on an M. tuberculosis background: ΔmosR and ΔechA7. These targeted genes are important to M. tuberculosis pathogenicity during infection. To examine the efficacy of these strains, C57BL/6 mice were vaccinated subcutaneously with either LAV, BCG, or PBS. Both LAV strains persisted up to 16 weeks in the spleens or lungs of vaccinated mice, while eliciting minimal pathology prior to challenge. Following challenge with a selected, high virulence M. tuberculosis Beijing strain, protection was notably greater for both groups of LAV vaccinated animals as compared to BCG at both 30 and 60 days post-challenge. Additionally, vaccination with either ΔmosR or ΔechA7 elicited an immune response similar to BCG. Although these strains require further development to meet safety standards, this first evidence of protection by these two new, live attenuated vaccine candidates shows promise.

  15. Transpressional deformation, strain partitioning and fold superimposition in the southern Chinese Altai, Central Asian Orogenic Belt

    NASA Astrophysics Data System (ADS)

    Li, Pengfei; Sun, Min; Rosenbaum, Gideon; Cai, Keda; Chen, Ming; He, Yulin

    2016-06-01

    Transpressional deformation has played an important role in the late Paleozoic evolution of the western Central Asian Orogenic Belt (CAOB), and understanding the structural evolution of such transpressional zones is crucial for tectonic reconstructions. Here we focus on the transpressional Irtysh Shear Zone with an aim at understanding amalgamation processes between the Chinese Altai and the West/East Junggar. We mapped macroscopic fold structures in the southern Chinese Altai and analyzed their relationships with the development of the adjacent Irtysh Shear Zone. Structural observations from these macroscopic folds show evidence for four generations of folding and associated fabrics. The earlier fabric (S1), is locally recognized in low strain areas, and is commonly isoclinally folded by F2 folds that have an axial plane orientation parallel to the dominant fabric (S2). S2 is associated with a shallowly plunging stretching lineation (L2), and defines ∼NW-SE tight-close upright macroscopic folds (F3) with the doubly plunging geometry. F3 folds are superimposed by ∼NNW-SSE gentle F4 folds. The F3 and F4 folds are kinematically compatible with sinistral transpressional deformation along the Irtysh Shear Zone and may represent strain partitioning during deformation. The sub-parallelism of F3 fold axis with the Irtysh Shear Zone may have resulted from strain partitioning associated with simple shear deformation along narrow mylonite zones and pure shear-dominant deformation (F3) in fold zones. The strain partitioning may have become less efficient in the later stage of transpressional deformation, so that a fraction of transcurrent components was partitioned into F4 folds.

  16. An interferon inducing porcine reproductive and respiratory syndrome virus vaccine candidate elicits protection against challenge with the heterologous virulent type 2 strain VR-2385 in pigs.

    PubMed

    Fontanella, Eve; Ma, Zexu; Zhang, Yanjin; de Castro, Alessandra M M G; Shen, Huigang; Halbur, Patrick G; Opriessnig, Tanja

    2017-01-03

    Achieving consistent protection by vaccinating pigs against porcine reproductive and respiratory syndrome virus (PRRSV) remains difficult. Recently, an interferon-inducing PRRSV vaccine candidate strain A2MC2 was demonstrated to be attenuated and induced neutralizing antibodies. The objective of this study was to determine the efficacy of passage 90 of A2MC2 (A2P90) to protect pigs against challenge with moderately virulent PRRSV strain VR-2385 (92.3% nucleic acid identity with A2MC2) and highly virulent atypical PRRSV MN184 (84.5% nucleic acid identity with A2MC2). Forty 3-week old pigs were randomly assigned to five groups including a NEG-CONTROL group (non-vaccinated, non-challenged), VAC-VR2385 (vaccinated, challenged with strain VR-2385), VR2385 (challenged with strain VR-2385), VAC-MN184 (vaccinated, challenged with strain MN184) and a MN184 group (challenged with MN184 virus). Vaccination was done at 3weeks of age followed by challenge at 8weeks of age. No viremia was detectable in any of the vaccinated pigs; however, by the time of challenge, 15/16 vaccinated pigs had seroconverted based on ELISA and had neutralizing antibodies against a homologous strain with titers ranging from 8 to 128. Infection with VR-2385 resulted in mild-to-moderate clinical disease and lesions. For VR-2385 infected pigs, vaccination significantly lowered PRRSV viremia and nasal shedding by 9days post challenge (dpc), significantly reduced macroscopic lung lesions, and significantly increased the average daily weight gain compared to the non-vaccinated pigs. Infection with MN184 resulted in moderate-to-severe clinical disease and lesions regardless of vaccination status; however, vaccinated pigs had significantly less nasal shedding by dpc 5 compared to non-vaccinated pigs. Under the study conditions, the A2P90 vaccine strain was attenuated without detectable shedding, improved weight gain, and offered protection to the pigs challenged with VR-2385 by reduction of virus load and

  17. Interleukin-6 Is Essential for Primary Resistance to Francisella tularensis Live Vaccine Strain Infection

    PubMed Central

    Kurtz, Sherry L.; Foreman, Oded; Bosio, Catharine M.; Anver, Miriam R.

    2013-01-01

    We employed Francisella tularensis live vaccine strain (LVS) to study mechanisms of protective immunity against intracellular pathogens and, specifically, to understand protective correlates. One potential molecular correlate identified previously was interleukin-6 (IL-6), a cytokine with pleotropic roles in immunity, including influences on T and B cell functions. Given its role as an immune modulator and the correlation with successful anti-LVS vaccination, we examined the role IL-6 plays in the host response to LVS. IL-6-deficient (IL-6 knockout [KO]) mice infected with LVS intradermally or intranasally or anti-IL-6-treated mice, showed greatly reduced 50% lethal doses compared to wild-type (WT) mice. Increased susceptibility was not due to altered splenic immune cell populations during infection or decreased serum antibody production, as IL-6 KO mice had similar compositions of each compared to WT mice. Although LVS-infected IL-6 KO mice produced much less serum amyloid A and haptoglobin (two acute-phase proteins) than WT mice, there were no other obvious pathophysiological differences between LVS-infected WT and IL-6 KO mice. IL-6 KO or WT mice that survived primary LVS infection also survived a high-dose LVS secondary challenge. Using an in vitro overlay assay that measured T cell activation, cytokine production, and abilities of primed splenocytes to control intracellular LVS growth, we found that IL-6 KO total splenocytes or purified T cells were slightly defective in controlling intracellular LVS growth but were equivalent in cytokine production. Taken together, IL-6 is an integral part of a successful immune response to primary LVS infection, but its exact role in precipitating adaptive immunity remains elusive. PMID:23230288

  18. Characterization of Chicken Splenic-Derived Dendritic Cells Following Vaccine and Very Virulent Strains of Infectious Bursal Disease Virus Infection.

    PubMed

    Yasmin, A R; Yeap, S K; Hair-Bejo, M; Omar, A R

    2016-12-01

    Studies have shown that infectious bursal disease virus (IBDV) infects lymphoid cells, mainly B cells and macrophages. This study was aimed to examine the involvement of chicken splenic-derived dendritic cells (ch-sDCs) in specific-pathogen-free chickens following inoculation with IBDV vaccine strain (D78) and a very virulent (vv) strain (UPM0081). Following IBDV infection, enriched activated ch-sDCs were collected by using the negative selection method and were examined based on morphology and immunophenotyping to confirm the isolation method for dendritic cells (DCs). The presence of IBDV on enriched activated ch-sDCs was analyzed based on the immunofluorescence antibody test (IFAT), flow cytometry, and quantitative real-time PCR (RT-qPCR) while the mRNAs of several cytokines were detected using RT-qPCR. The isolated ch-sDCs resembled typical DC morphologies found in mammals by having a veiled shape and they grew in clusters. Meanwhile, the expression of DC maturation markers, namely CD86 and MHCII, were increased at day 2 and day 3 following vvIBDV and vaccine strain inoculation, respectively, ranging from 10% to 40% compared to the control at 2.55% (P < 0.05). At day 3 postinfection, IBDV VP3 proteins colocalized with CD86 were readily detected via IFAT and flow cytometry in both vaccine and vvIBDV strains. In addition, enriched activated ch-sDCs were also detected as positive based on the VP4 gene by RT-qPCR; however, a higher viral load was detected on vvIBDV compared to the vaccine group. Infection with vaccine and vvIBDV strains induced the enriched activated ch-sDCs to produce proinflammatory cytokines and Th1-like cytokines from day 3 onward; however, the expressions were higher in the vvIBDV group (P < 0.05). These data collectively suggest that enriched activated ch-sDCs were permissive to IBDV infection and produced a strong inflammatory and Th1-like cytokine response following vvIBDV infection as compared to the vaccine strain.

  19. Rotavirus strain surveillance for three years following the introduction of rotavirus vaccine into Belém, Brazil.

    PubMed

    Guerra, Sylvia F S; Linhares, Alexandre C; Mascarenhas, Joana D'Arc P; Oliveira, Alessilva; Justino, Maria Cleonice A; Soares, Luana S; Müller, Elza Caroline; Brasil, Patrícia; Tuboi, Suely; Ortega-Barria, Eduardo; Colindres, Rómulo

    2015-08-01

    The monovalent human rotavirus (RV) vaccine, RIX4414 (Rotarix™, GlaxoSmithKline Biologicals) was introduced into Brazil's Expanded Program on Immunization in March 2006. One year after vaccine introduction, the G2P[4] strain was found to be predominant, with an apparent extinction of many non-G2 strains. This study investigated the diversity of circulating strains in the three years following RIX4414 introduction. Between May 2008 and May 2011, stool samples were collected from children aged ≥12 weeks who were hospitalized for severe lab confirmed RV-gastroenteritis (≥3 liquid or semi-liquid motions over a 24-h period for <14 days, requiring ≥1 overnight hospital stay and intravenous rehydration therapy) in Belém, Brazil. RV-gastroenteritis was detected by ELISA and the G- and P-types were determined by RT-PCR assays. During the first year of surveillance nucleotide sequencing was used for typing those samples not previously typed by RT-PCR. A total of 1,726 of 10,030 severe gastroentertis hospitalizations (17.2%) were due to severe RVGE. G2P[4] was detected in 57.2% of circulating strains over the whole study period, however it predominated during the first 20 months from May 2008 to January 2009. G1P[8] increased in the last part of the study period from May 2010 to May 2011 and represented 36.6% (112/306) of the circulating strains. G2P[4] was the predominant RV strain circulating during the first 20 months of the study, followed by G1P[8]. These findings probably reflect a natural fluctuation in RV strains over time, rather than a vaccine-induced selective pressure.

  20. [Vaccination].

    PubMed

    Graubner, U B; Liese, J; Belohradsky, B H

    2001-09-01

    Vaccination has been an important part of antiinfectious prophylaxis in pediatric oncology comprising immunizations with special indication like varicella vaccine and follow-up of routine immunizations after chemotherapy and bone marrow transplantation (BMT). Studies from the last decade demonstrate a loss of long term immunity to immunization preventable disease in most patients with chemotherapy and BMT who had received appropriate immunization before. So far routine vaccination programs following intensive chemotherapy have not been studied prospectively. Immunization programs following BMT have shown that immunizations with tetanus toxoid, diphtheria toxoid, inactivated poliovirus vaccine and influenza vaccine - given at least 12 months after transplantation - are safe and effective. Vaccination with live attenuated trivalent vaccine against measles, mumps and rubella in patients without chronic "graft versus host disease" (GVHD) and without ongoing immunosuppressive therapy, performed 24 months after transplantation, proved to be safe too. Recommendations have been published by 5 different official groups: (1.) "Ständige Impfkommission" (STIKO) and (2.) "Deutsche Gesellschaft für pädiatrische Infektiologie" (DGPI) recommend varicella vaccine für children with leukemia in remission for at least 12 months, for children with solid tumors and for patients getting an organ transplantation. Both societies do not comment on the schedule of booster vaccinations (with live attenuated vaccines) after the end of chemotherapy and after BMT. (3.) "Qualitätssicherungsgruppe" der "Gesellschaft für pädiatrische Onkologie und Hämatologie" (QS-GPOH) recommends immunization with nonliving vaccines when the patient is off therapy for at least 3 months and immunization with live attenuated vaccines when he is off therapy for at least 6 months. This group does not comment on varicella vaccine which has been controversial among pediatric oncologists. (4.) The " Infectious

  1. Fitness cost, gyrB mutation, and absence of phosphotransferase system fructose specific IIABC component in novobiocin-resistant Streptococcus iniae vaccine strain ISNO

    USDA-ARS?s Scientific Manuscript database

    To understand the fitness cost of novobiocin-resistance in an attenuated Streptococcus iniae vaccine strain ISNO compared to its virulent parent strain ISET0901, cell proliferation rate of the two strains were compared to each other. Our results revealed that the cell proliferation rates of ISNO wer...

  2. Effect of polymyxin B and environmental conditions on isolation of Brucella species and the vaccine strain RB51.

    PubMed

    Jensen, Allen E; Halling, Shirley M

    2010-03-01

    Brucella are resistant to polymyxin B (PB), but their relative susceptibility to PB and its derivative, colistin (COL) has not been rigorously or systematically studied. Comparative susceptibility of Brucella reference strains, vaccine strain RB51, and Brucella isolates from marine mammals to these two cationic peptides were determined by Etest. Vast differences among Brucella species were found in susceptibility to both PB and COL. Brucella demonstrated similar pattern of relative susceptibility to PB as that of COL, but they were less susceptible to COL. Both B. melitensis and B. suis were the least susceptible to polymyxins and rough strains were more susceptible to both PB and COL than the smooth except for the BvrR mutant. Strains were generally less susceptible to PB when cultured in CO(2) rather than ambient air; some became more susceptible in acidified medium. Results show that environment cultural conditions must be considered when selecting for CO(2)-independent strains of Brucella especially the vaccine strain RB51 on selective media containing PB. Our observations extend basic knowledge of the differential resistance of Brucella to polymyxins.

  3. Immunogenicity and reactogenicity of the human rotavirus vaccine, RIX4414 oral suspension, when co-administered with routine childhood vaccines in Chinese infants

    PubMed Central

    Li, Rong-cheng; Huang, Teng; Li, Yanping; Wang, Lao-Hong; Tao, Junhui; Fu, Botao; Si, Guoai; Nong, Yi; Mo, Zhaojun; Liao, XueYan; Luan, Ivy; Tang, Haiwen; Rathi, Niraj; Karkada, Naveen; Han, Htay Htay

    2016-01-01

    Abstract This study evaluated the immunogenicity of the human rotavirus (RV) vaccine (RIX4414) when co-administered with routine childhood vaccines in Chinese infants (NCT01171963). Healthy infants aged 6–16 weeks received 2 doses of either RIX4414 or placebo according to a 0, 1-month schedule. Infants received routine diphtheria-tetanus-acellular pertussis (DTPa) and oral poliovirus (OPV) vaccines either separately from or concomitantly with RIX4414/placebo (separate and co-administration cohorts, respectively). Anti-RV IgA seroconversion rates (one month post-dose-2) and seropositivity rates (at one year of age) were measured using ELISA. Immune responses against the DTPa and OPV antigens were measured one month post-DTPa dose-3 in the co-administration cohort. Solicited local and general symptoms were recorded for 8-days post-vaccination (total cohort). The according-to-protocol immunogenicity population included 511 infants in the separate cohort and 275 in the co-administration cohort. One month post-RIX4414 dose-2, anti-RV IgA seroconversion rates were 74.7% (95% confidence interval [CI]: 68.9–79.9) and 64.2% (95% CI: 55.4–72.3) in the separate and co-administration cohorts; seropositivity rates at one year of age were 71.5% (95% CI: 65.5–77.1) and 50.0% (95% CI: 40.9–59.1), respectively. One month post-DTPa dose-3, all infants in the co-administration cohort were seroprotected against diphtheria and tetanus, and seropositive for pertussis toxoid, pertactin and filamentous haemaglutinin. Two months post-OPV dose-3, seroprotection rates against anti-poliovirus types 1, 2 and 3 were >99% in the co-administration cohort. Reactogenicity profiles were similar in both cohorts. RIX4414 was immunogenic and well-tolerated in Chinese infants and did not appear to interfere with the immunogenicity and reactogenicity of co-administered routine childhood vaccines. PMID:27149266

  4. Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

    DTIC Science & Technology

    2006-10-01

    considered to have potential as a biological weapon. Recently, we reported the development of a promising attenuated, replication -competent vaccine against...MARV infections, we recently described the development of a promising new replication -competent vaccine against MARV based on recombinant vesicular...reported the development of a promising attenuated, replication -competent vaccine against MARV based on recombinant vesicular stomatitis virus (VSV

  5. Development of a novel vaccine against canine parvovirus infection with a clinical isolate of the type 2b strain

    PubMed Central

    Park, Seon Ah; Park, Seung-Yong; Song, Chang-Seon; Choi, In-Soo; Kim, Hwi Yool; Lee, Joong-Bok

    2012-01-01

    Purpose In spite of an extensive vaccination program, parvoviral infections still pose a major threat to the health of dogs. Materials and Methods We isolated a novel canine parvovirus (CPV) strain from a dog with enteritis. Nucleotide and amino acid sequence analysis of the isolate showed that it is a novel type 2b CPV with asparagine at the 426th position and valine at the 555th position in VP2. To develop a vaccine against CPV infection, we passaged the isolate 4 times in A72 cells. Results The attenuated isolate conferred complete protection against lethal homologous CPV infection in dogs such that they did not develop any clinical symptoms, and their antibody titers against CPV were significantly high at 7-11 days post infection. Conclusion These results suggest that the virus isolate obtained after passaging can be developed as a novel vaccine against paroviral infection. PMID:23596579

  6. Mosaic vaccines elicit CD8+ T cell responses in monkeys that confer immune coverage of diverse HIV strains

    SciTech Connect

    Fischer, Will; Korber, Bette

    2009-01-01

    Creation of a successful HIV vaccine will require the development of a strategy to generate cellular immunity with sufficient cross-clade breadth to deal with the extreme genetic diversity of the virus. Polyvalent mosaic immunogens derived from in silica recombination of natural strains of HIV are designed to induce cellular immune responses that maximally cover the sequence diversity of circulating virus isolates. Immunization of rhesus monkeys with plasmid DNA and recombinant vaccinia virus vaccine constructs expressing either consensus immunogens or polyvalent mosaic immunogens elicited a CD4+ T lymphocyte-biased response with comparably broad epitope-specific total T lymphocyte specificities. However, immunization with the mosaic immunogens induced HIV-specific CD8+ T lymphocyte responses with markedly greater depth and breadth. Therefore, the use of polyvalent mosaic immunogens is a promising strategy for a global vaccine for HIV.

  7. Comparison of two real-time RT-PCR assays for differentiation of C-strain vaccinated from classical swine fever infected pigs and wild boars.

    PubMed

    Widén, F; Everett, H; Blome, S; Fernandez Pinero, J; Uttenthal, A; Cortey, M; von Rosen, T; Tignon, M; Liu, L

    2014-10-01

    Classical swine fever is one of the most important infectious diseases for the pig industry worldwide due to its economic impact. Vaccination is an effective means to control disease, however within the EU its regular use is banned owing to the inability to differentiate infected and vaccinated animals, the so called DIVA principle. This inability complicates monitoring of disease and stops international trade thereby limiting use of the vaccine in many regions. The C-strain vaccine is safe to use and gives good protection. It is licensed for emergency vaccination in the EU in event of an outbreak. Two genetic assays that can distinguish between wild type virus and C-strain vaccines have recently been developed. Here the results from a comparison of these two real-time RT-PCR assays in an interlaboratory exercise are presented. Both assays showed similar performance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Clinical and serologic effects of Alice strain live attenuated influenza A (H3N2) virus vaccine in an adult population.

    PubMed

    Miller, L W; Togo, Y; Hornick, R B

    1975-12-30

    Alice strain live attenuated influenza A (H3N2) virus was evaluated in prison volunteers. By random double blind allocation, 94 volunteers received Alice strain vaccine (AS) intranasally and 97 received placebo. The vaccine was well tolerated, and there was no serious morbidity. The number, type, duration, and severity of symptoms was not significantly different between the vaccine and placebo groups. Seventy-five per cent of vaccines with initial HAI titers less than or equal to 1:8 had 4 fold or greater titer responses on day 30. Placebo recipients experienced no titer changes. The GMT among vaccinees increased from 23.5 prior to vaccination 59.7 30 days later. Surveillance activities failed to document influenza A (H3N2) infection in the volunteer population during a 6 month follow-up period. Additional studies on the protective effects of the vaccine are required before efficacy can be determined.

  9. Efficacy of an Escherichia coli O157:H7 SRP Vaccine in Orally Challenged Goats and Strain Persistence Over Time.

    PubMed

    Swift, Jacob M; Foster, Derek M; Rogers, Anna T; Sylvester, Hannah J; Griffith, Emily H; Jacob, Megan E

    2017-03-01

    Small ruminants have been implicated in outbreaks of Escherichia coli O157:H7 at livestock exhibitions throughout the United States. Additionally, goat meat or milk may serve as a reservoir for foodborne transmission of the organism. These associations highlight the public health importance of an effective strategy to reduce E. coli O157:H7 shedding in goats. We examined the efficacy of the SRP(®) vaccine in goats orally challenged with E. coli O157:H7. Mixed-breed goats (n = 14) were randomly allocated into vaccinated and unvaccinated treatments (n = 7 per treatment). Goats were housed with a vaccinated and unvaccinated animal in each pen. Feces were collected for 3 weeks, then at necropsy, gastrointestinal contents were collected to determine the concentration of E. coli O157:H7. Three isolates per positive sample were saved and evaluated by pulsed-field gel electrophoresis (PFGE) to assess strain persistence over time. The mean concentration of E. coli O157:H7 in the feces of goats was numerically reduced in the vaccinated treatment; however, it was not statistically significant. In addition, the total number of days goats were fecal positive for E. coli O157:H7 were not different between vaccinated and unvaccinated treatments. Pulsotypes of isolates revealed that goats initially shed two of the four challenge strains of E. coli O157:H7, after which there was a distinct shift to two different strains. Further work is needed to evaluate cost-effective intervention strategies that reliably reduce E. coli O157:H7 shedding in goats, particularly those that may reduce the risk of transmission at public events, including petting zoos and fairs.

  10. Selected prfA* mutations in recombinant attenuated Listeria monocytogenes strains augment expression of foreign immunogens and enhance vaccine-elicited humoral and cellular immune responses.

    PubMed

    Yan, Lin; Qiu, Jin; Chen, Jianbo; Ryan-Payseur, Bridgett; Huang, Dan; Wang, Yunqi; Rong, Lijun; Melton-Witt, Jody A; Freitag, Nancy E; Chen, Zheng W

    2008-08-01

    While recombinant Listeria monocytogenes strains can be explored as vaccine candidates, it is important to develop attenuated but highly immunogenic L. monocytogenes vaccine vectors. Here, prfA* mutations selected on the basis of upregulated expression of L. monocytogenes PrfA-dependent genes and proteins were assessed to determine their abilities to augment expression of foreign immunogens in recombinant L. monocytogenes vectors and therefore enhance vaccine-elicited immune responses (a prfA* mutation is a mutation that results in constitutive overexpression of PrfA and PrfA-dependent virulence genes; the asterisk distinguishes the mutation from inactivation or stop mutations). A total of 63 recombinant L. monocytogenes vaccine vectors expressing seven individual viral or bacterial immunogens each in nine different L. monocytogenes strains carrying wild-type prfA or having prfA* mutations were constructed and investigated. Mutations selected on the basis of increased PrfA activation in recombinant L. monocytogenes prfA* vaccine vectors augmented expression of seven individual protein immunogens remarkably. Consistently, prime and boost vaccination studies with mice indicated that the prfA(G155S) mutation in recombinant L. monocytogenes DeltaactA prfA* strains enhanced vaccine-elicited cellular immune responses. Surprisingly, the prfA(G155S) mutation was found to enhance vaccine-elicited humoral immune responses as well. The highly immunogenic recombinant L. monocytogenes DeltaactA prfA* vaccine strains were as attenuated as the recombinant parent L. monocytogenes DeltaactA vaccine vector. Thus, recombinant attenuated L. monocytogenes DeltaactA prfA* vaccine vectors potentially are better antimicrobial and anticancer vaccines.

  11. Construction of a Vibrio cholerae prototype vaccine strain O395-N1-E1 which accumulates cell-associated cholera toxin B subunit.

    PubMed

    Rhie, Gi-eun; Jung, Hae-Mi; Kim, Bong Su; Mekalanos, John J

    2008-10-09

    Because of its production and use in Vietnam, the most widely used oral cholera vaccine consists of heat- or formalin-killed Vibrio cholerae whole cells (WC). An earlier version of this type of vaccine called whole cell-recombinant B subunit vaccine (BS-WC) produced in Sweden also contained the B subunit of cholera toxin (CTB). Both WC and BS-WC vaccines produced moderate levels of protection in field trials designed to evaluate their cholera efficacy. V. cholerae cells in these vaccines induce antibacterial immunity, and CTB contributes to the vaccine's efficacy presumably by stimulating production of anti-toxin neutralizing antibody. Although more effective than the WC vaccine, the BS-WC vaccine has not been adopted for manufacture by developing world countries primarily because the CTB component is difficult to manufacture and include in the vaccine in the doses needed to induce significant immune responses. We reasoned this was a technical problem that might be solved by engineering strains of V. cholerae that express cell-associated CTB that would co-purify with the bacterial cell fraction during the manufacture of WC vaccine. Here we report that construction of a V. cholerae O1 classical strain, O395-N1-E1, that has been engineered to accumulate CTB in the periplasmic fraction by disrupting the epsE gene of type II secretion pathway. O395-N1-E1 induces anti-CTB IgG and vibriocidal antibodies in mice immunized with two doses of formalin killed whole cells. Intraperitoneal immunization of mice with O395-N1-E1 induced a significantly higher anti-CTB antibody response compared to that of the parental strain, O395-N1. Our results suggest that this prototype cholera vaccine candidate strain may assist in preparing improved and inexpensive oral BS-WC cholera vaccine without the need to purify CTB separately.

  12. Leptospirosis vaccines

    PubMed Central

    Wang, Zhijun; Jin, Li; Węgrzyn, Alicja

    2007-01-01

    Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP) vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool. PMID:18072968

  13. Global Panel of HIV-1 Env Reference Strains for Standardized Assessments of Vaccine-Elicited Neutralizing Antibodies

    PubMed Central

    deCamp, Allan; Hraber, Peter; Bailer, Robert T.; Seaman, Michael S.; Ochsenbauer, Christina; Kappes, John; Gottardo, Raphael; Edlefsen, Paul; Self, Steve; Tang, Haili; Greene, Kelli; Gao, Hongmei; Daniell, Xiaoju; Sarzotti-Kelsoe, Marcella; Gorny, Miroslaw K.; Zolla-Pazner, Susan; LaBranche, Celia C.; Mascola, John R.; Korber, Bette T.

    2014-01-01

    ABSTRACT Standardized assessments of HIV-1 vaccine-elicited neutralizing antibody responses are complicated by the genetic and antigenic variability of the viral envelope glycoproteins (Envs). To address these issues, suitable reference strains are needed that are representative of the global epidemic. Several panels have been recommended previously, but no clear answers have been available on how many and which strains are best suited for this purpose. We used a statistical model selection method to identify a global panel of reference Env clones from among 219 Env-pseudotyped viruses assayed in TZM-bl cells with sera from 205 HIV-1-infected individuals. The Envs and sera were sampled globally from diverse geographic locations and represented all major genetic subtypes and circulating recombinant forms of the virus. Assays with a panel size of only nine viruses adequately represented the spectrum of HIV-1 serum neutralizing activity seen with the larger panel of 219 viruses. An optimal panel of nine viruses was selected and augmented with three additional viruses for greater genetic and antigenic coverage. The spectrum of HIV-1 serum neutralizing activity seen with the final 12-virus panel closely approximated the activity seen with subtype-matched viruses. Moreover, the final panel was highly sensitive for detection of many of the known broadly neutralizing antibodies. For broader assay applications, all 12 Env clones were converted to infectious molecular clones using a proviral backbone carrying a Renilla luciferase reporter gene (Env.IMC.LucR viruses). This global panel should facilitate highly standardized assessments of vaccine-elicited neutralizing antibodies across multiple HIV-1 vaccine platforms in different parts of the world. IMPORTANCE An effective HIV-1 vaccine will need to overcome the extraordinary genetic variability of the virus, where most variation occurs in the viral envelope glycoproteins that are the sole targets for neutralizing antibodies

  14. Knowledge and Awareness of Cervical Cancer, Human Papillomavirus (HPV), and HPV Vaccine Among HPV-Infected Chinese Women.

    PubMed

    Baloch, Zulqarnain; Yasmeen, Nafeesa; Li, Yuanyue; Zhang, Wenhui; Lu, Hongyu; Wu, Xiaomei; Xia, Xueshan; Yang, Shihua

    2017-09-04

    BACKGROUND It is important to understand the knowledge that various groups of a population have about cervical cancer and human papillomavirus (HPV) and their attitudes toward HPV vaccination, as it will ultimately influence their decision-making for or against the acceptability of vaccines and other preventive methods. This study was designed to determine the level of knowledge and awareness about cervical cancer, HPV, and the HPV vaccine among Chinese women in Yunnan province. MATERIAL AND METHODS A survey was conducted in Yunnan province by the Laboratory of Molecular Virology in collaboration with the Yunnan First People's Hospital in Feb 2015. A total of 388 women were recruited and asked to participate in a questionnaire-based interview that collected information related to their awareness and knowledge about: (1) cervical cancer, (2) HPV and HPV vaccine and willingness to have their children receive vaccination, and (3) demographic characteristics. RESULTS A total of 388 HPV-positive women were included; 300/388 (73.3%) were Han, and 88/388 (22.7%) were other ethnicities. Overall, 204/388 (52.6%) of the women were aware of cervical cancer, with a significant difference between Han women and women of other ethnic groups (168/388, 56.0% and 36/88, 40.9%; P=0.015). Overall, 26.5% of the women were aware of the role of HPV in cervical cancer; 29.0% of the Han women and 18.2% of women of other ethnic groups were aware of this role of HPV (P=0.05). The knowledge that HPV infection leads to cervical cancer was higher among Han women (29.0%) compared to women of other ethnicities (18.2%). Knowledge about the HPV vaccine was very low in all ethnic groups, but the Han women were more willing to allow their children to be vaccinated before they become sexually active. A similar difference has also been found in women from various regions. CONCLUSIONS Although level of awareness and knowledge about cervical cancer was moderate, knowledge and awareness of HPV and the HPV

  15. Perceptions of Hong Kong Chinese women toward influenza vaccination during pregnancy.

    PubMed

    Yuen, Carol Y S; Dodgson, Joan E; Tarrant, Marie

    2016-01-02

    Pregnant women are the highest priority group for seasonal influenza vaccination. However, their vaccination uptake remains suboptimal. The purpose of this study is to explore Hong Kong women's perceptions of the threat of influenza infection during pregnancy, the risks and benefits of influenza vaccination, and their decision-making processes. We used a qualitative descriptive design and recruited women who had just given births to a live infant from April to June 2011. Participants were recruited from a large teaching hospital in Hong Kong and were interviewed in the immediate postpartum period. A total of 32 postpartum women were interviewed, and two had been vaccinated during pregnancy. Following thematic analysis, three themes emerged: perceived risk of influenza infection, perceived risk of influenza vaccine, and decision-making cues. Overall, participants held negative impressions about influenza vaccination during pregnancy, and they underestimated the threat of influenza to themselves and their fetus. They were also confused about the safety and efficacy of the influenza vaccine and the differences between preventive strategies and treatment for influenza. Most participants reported that their health care providers (HCPs) did not offer or recommend vaccination. Because of negative media reports about vaccination, participants were hesitant to receive the vaccine. Motivating forces for vaccine acceptance were a perceived high prevalence of circulating influenza during their pregnancy and HCP recommendations and reassurances that the vaccination was safe, effective, and beneficial for the fetus. Vaccination promotion strategies need to focus on encouraging HCPs to take the initiative to discuss vaccination with their pregnant clients and provide accurate and unbiased information about the risks of influenza and the benefits of vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. GroEL and Lipopolysaccharide from Francisella tularensis Live Vaccine Strain Synergistically Activate Human Macrophages ▿

    PubMed Central

    Noah, Courtney E.; Malik, Meenakshi; Bublitz, DeAnna C.; Camenares, Devin; Sellati, Timothy J.; Benach, Jorge L.; Furie, Martha B.

    2010-01-01

    Francisella tularensis, the causative agent of tularemia, interacts with host cells of innate immunity in an atypical manner. For most Gram-negative bacteria, the release of lipopolysaccharide (LPS) from their outer membranes stimulates an inflammatory response. When LPS from the attenuated live vaccine strain (LVS) or the highly virulent Schu S4 strain of F. tularensis was incubated with human umbilical vein endothelial cells, neither species of LPS induced expression of the adhesion molecule E-selectin or secretion of the chemokine CCL2. Moreover, a high concentration (10 μg/ml) of LVS or Schu S4 LPS was required to stimulate production of CCL2 by human monocyte-derived macrophages (huMDM). A screen for alternative proinflammatory factors of F. tularensis LVS identified the heat shock protein GroEL as a potential candidate. Recombinant LVS GroEL at a concentration of 10 μg/ml elicited secretion of CXCL8 and CCL2 by huMDM through a TLR4-dependent mechanism. When 1 μg of LVS GroEL/ml was added to an equivalent amount of LVS LPS, the two components synergistically activated the huMDM to produce CXCL8. Schu S4 GroEL was less stimulatory than LVS GroEL and showed a lesser degree of synergy when combined with Schu S4 LPS. These findings suggest that the intrinsically low proinflammatory activity of F. tularensis LPS may be increased in the infected human host through interactions with other components of the bacterium. PMID:20123721

  17. Comparative evaluation of cell culture-adapted and chicken embryo-adapted fowl pox vaccine strains.

    PubMed

    Baxi, M K; Oberoi, M S

    1999-01-01

    Two types of vaccines, chicken embryo adapted (VacCE) and cell culture adapted (VacCC), were tested for their efficacy to elicite the immune response in birds vaccinated at 2 and 8 wk of age. The cell-mediated immune response studied by blastogenesis assay showed that birds vaccinated at the second week of age by both VacCE and VacCC vaccines had significant increase in T-lymphocyte count at 21 days postvaccination (PV) and 7 days postchallenge (PC), whereas in birds vaccinated at 8 wk of age, a significant increase was seen at 21 days PV and 7 days PC with the VacCC vaccine. The rise in passive hemagglutination titers was observed up to 21 days PV and 7 days PC in birds vaccinated at 2 wk of age. However, only the birds vaccinated with VacCC at 8 wk of age showed rise in titers at days 21 PV and 7 PC. Birds were challenged 90 days PV by scarification on the thigh region, and the birds vaccinated with VacCC showed 90% and 70% protection when vaccinated at 2 and 8 wk, respectively. The birds vaccinated with VacCE showed only 60% and 20% protection at the corresponding levels, respectively.

  18. Biocontrol of geosmin-producing Streptomyces spp. by two Bacillus strains from Chinese liquor.

    PubMed

    Zhi, Yan; Wu, Qun; Du, Hai; Xu, Yan

    2016-08-16

    Streptomyces spp. producing geosmin have been regarded as the most frequent and serious microbial contamination causing earthy off-flavor in Chinese liquor. It is therefore necessary to control the Streptomyces community during liquor fermentation. Biological control, using the native microbiota present in liquor making, appears to be a better solution than chemical methods. The objective of this study was to isolate native microbiota antagonistic toward Streptomyces spp. and then to evaluate the possible action mode of the antagonists. Fourteen Bacillus strains isolated from different Daqu (the fermentation starter) showed antagonistic activity against Streptomyces sampsonii, which is one of the dominant geosmin producers. Bacillus subtilis 2-16 and Bacillus amyloliquefaciens 1-45 from Maotai Daqu significantly inhibited the growth of S. sampsonii by 57.8% and 84.3% respectively, and effectively prevented the geosmin production in the simulated fermentation experiments (inoculation ratio 1:1). To probe the biocontrol mode, the ability of strain 2-16 and 1-45 to produce antimicrobial metabolites and to reduce geosmin in the fermentation system was investigated. Antimicrobial substances were identified as lipopeptides by ultra-performance liquid chromatography tandem electrospray ionization/quadrupole-time-of-flight mass spectrometry (UPLC-ESI/Q-TOF MS) and in vitro antibiotic assay. In addition, strains 2-16 and 1-45 were able to remove 45% and 15% of the geosmin respectively in the simulated solid-state fermentation. This study highlighted the potential of biocontrol, and how the use of native Bacillus species in Daqu could provide an eco-friendly method to prevent growth of Streptomyces spp. and geosmin contamination in Chinese liquor fermentation.

  19. Single dose vaccination of the ASO3-adjuvanted A(H1N1)pdm09 monovalent vaccine in health care workers elicits homologous and cross-reactive cellular and humoral responses to H1N1 strains

    PubMed Central

    Lartey, Sarah; Pathirana, Rishi D; Zhou, Fan; Jul-Larsen, Åsne; Montomoli, Emanuele; Wood, John; Cox, Rebecca Jane

    2015-01-01

    Healthcare workers (HCW) were prioritized for vaccination during the 2009 influenza A(H1N1)pdm09 pandemic. We conducted a clinical trial in October 2009 where 237 HCWs were immunized with a AS03-adjuvanted A(H1N1)pdm09 monovalent vaccine. In the current study, we analyzed the homologous and cross-reactive H1N1 humoral responses using prototype vaccine strains dating back to 1977 by the haemagglutinin inhibition (HI), single radial hemolysis SRH), antibody secreting cell (ASC) and memory B cell (MBC) assays. The cellular responses were assessed by interferon-γ (IFN-γ) ELISPOT and by intracellular staining (ICS) for the Th1 cytokines IFN-γ, interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α). All assays were performed using blood samples obtained prior to (day 0) and 7, 14 and 21 d post-pandemic vaccination, except for ASC (day 7) and ICS (days 0 and 21). Vaccination elicited rapid HI, SRH and ASC responses against A(H1N1)pdm09 which cross reacted with seasonal H1N1 strains. MBC responses were detected against the homologous and seasonal H1N1 strains before vaccination and were boosted 2 weeks post-vaccination. An increase in cellular responses as determined by IFN-γ ELISPOT and ICS were observed 1–3 weeks after vaccination. Collectively, our data show that the AS03-adjuvanted A(H1N1)pdm09 vaccine induced rapid cellular and humoral responses against the vaccine strain and the response cross-reacted against prototype H1N1 strains dating back to 1977. PMID:26009966

  20. Identification of Brucella melitensis Rev.1 vaccine-strain genetic markers: Towards understanding the molecular mechanism behind virulence attenuation.

    PubMed

    Issa, Mohammad Nouh; Ashhab, Yaqoub

    2016-09-22

    Brucella melitensis Rev.1 is an avirulent strain that is widely used as a live vaccine to control brucellosis in small ruminants. Although an assembled draft version of Rev.1 genome has been available since 2009, this genome has not been investigated to characterize this important vaccine. In the present work, we used the draft genome of Rev.1 to perform a thorough genomic comparison and sequence analysis to identify and characterize the panel of its unique genetic markers. The draft genome of Rev.1 was compared with genome sequences of 36 different Brucella melitensis strains from the Brucella project of the Broad Institute of MIT and Harvard. The comparative analyses revealed 32 genetic alterations (30 SNPs, 1 single-bp insertion and 1 single-bp deletion) that are exclusively present in the Rev.1 genome. In silico analyses showed that 9 out of the 17 non-synonymous mutations are deleterious. Three ABC transporters are among the disrupted genes that can be linked to virulence attenuation. Out of the 32 mutations, 11 Rev.1 specific markers were selected to test their potential to discriminate Rev.1 using a bi-directional allele-specific PCR assay. Six markers were able to distinguish between Rev.1 and a set of control strains. We succeeded in identifying a panel of 32 genome-specific markers of the B. melitensis Rev.1 vaccine strain. Extensive in silico analysis showed that a considerable number of these mutations could severely affect the function of the associated genes. In addition, some of the discovered markers were able to discriminate Rev.1 strain from a group of control strains using practical PCR tests that can be applied in resource-limited settings.

  1. Recombinant infectious bronchitis virus (IBV) H120 vaccine strain expressing the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) protects chickens against IBV and NDV challenge.

    PubMed

    Yang, Xin; Zhou, Yingshun; Li, Jianan; Fu, Li; Ji, Gaosheng; Zeng, Fanya; Zhou, Long; Gao, Wenqian; Wang, Hongning

    2016-05-01

    Infectious bronchitis (IB) and Newcastle disease (ND) are common viral diseases of chickens, which are caused by infectious bronchitis virus (IBV) and Newcastle disease virus (NDV), respectively. Vaccination with live attenuated strains of IBV-H120 and NDV-LaSota are important for the control of IB and ND. However, conventional live attenuated vaccines are expensive and result in the inability to differentiate between infected and vaccinated chickens. Therefore, there is an urgent need to develop new efficacious vaccines. In this study, using a previously established reverse genetics system, we generated a recombinant IBV virus based on the IBV H120 vaccine strain expressing the haemagglutinin-neuraminidase (HN) protein of NDV. The recombinant virus, R-H120-HN/5a, exhibited growth dynamics, pathogenicity and viral titers that were similar to those of the parental IBV H120, but it had acquired hemagglutination activity from NDV. Vaccination of SPF chickens with the R-H120-HN/5a virus induced a humoral response at a level comparable to that of the LaSota/H120 commercial bivalent vaccine and provided significant protection against challenge with virulent IBV and NDV. In summary, the results of this study indicate that the IBV H120 strain could serve as an effective tool for designing vaccines against IB and other infectious diseases, and the generation of IBV R-H120-HN/5a provides a solid foundation for the development of an effective bivalent vaccine against IBV and NDV.

  2. A gE-negative bovine herpesvirus 1 vaccine strain is not re-excreted nor transmitted in an experimental cattle population after corticosteroid treatments.

    PubMed

    Mars, M H; de Jong, M C; van Oirschot, J T

    2000-04-03

    To study possible reactivation and to quantify subsequent transmission of a live gE-negative bovine herpesvirus 1 (BHV1) vaccine strain in cattle populations, four experiments were performed. Two groups of cattle were each tested twice for the possibility of reactivation. Inoculation with a gE-negative BHV1 vaccine was done either intramuscularly or intranasally and treatment with corticosteroids in an attempt to reactivate vaccine virus, was done after 6 or 11 weeks, and again after 6 months. To quantify transmission of vaccine virus following possible reactivation, each cattle was housed together with one susceptible contact-cattle. Contact-infections were monitored using virus shedding and antibody responses. After corticosteroid treatments, re-excretion of virus was never detected in cattle that had been inoculated with the gE-negative BHV1 vaccine strain. Contact cattle did not shed gE-negative BHV1, nor mounted any antibody response against BHV1. In contrast, positive control cattle, inoculated intranasally with wild-type BHV1, re-excreted virus in high titers in nasal fluids and transmitted the virus to contact cattle. Based on these results, the transmission ratio R(0) of the vaccine strain was zero. We concluded that it is highly unlikely that the live gE-negative BHV1 vaccine strain will be re-excreted after possible reactivation, and consequently, it is even less likely that reactivated vaccine virus will spread in the cattle population.

  3. Emergence of antigenic variants of Foot-and-Mouth Disease Virus serotype O in Ecuador and preliminary evaluation of a field strain as a vaccine candidate.

    PubMed

    Maradei, Eduardo; Malirat, Viviana; Beascoechea, Claudia Perez; Espinoza, Ana María; Novo, Sabrina Galdo; Smitsaart, Eliana; Salgado, Gustavo; Mattion, Nora; Toledo, Jorge Rodriguez; Bergmann, Ingrid E

    2014-05-01

    Foot-and-Mouth Disease Virus serotype O has been circulating regularly throughout most provinces of Ecuador, one of the two South American countries that still remain endemic, although satisfactory vaccination coverage was reported. This study concentrates in the characterization of isolates collected during 2008-2011, focusing particularly on the antigenic and immunogenic relationships of the field viruses with the O1/Campos vaccine strain in use in the region and with an experimental vaccine formulated with a representative strain of the 2010 epidemic. The results established that antigenically divergent variants poorly protected by the vaccine in use emerged and co-circulated in a limited period of time. A monovalent vaccine formulated with the representative 2010 strain elicited high antibody titers and protected against challenge with homologous virus. In addition, cross-reactive antibodies to predominant viruses in the region were established. In overall this study indicates the ability of the virus to diversify under field conditions in which a vaccine strain with poor match is applied, and the potential of the selected 2010 field virus as a vaccine candidate for incorporation into strategic antigen banks and/or for addition to current formulations for systematic vaccination, in order to prevent the emergence of even more divergent isolates in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Serological response to administration of Brucella abortus strain RB51 vaccine in beef and dairy heifers, using needle-free and standard needle-based injection systems

    USDA-ARS?s Scientific Manuscript database

    The purpose of this study was to compare immunologic responses of heifers vaccinated with 10**10 colony-forming units (CFU) of Brucella abortus strain RB51 (SRB51) by standard needle-and-syringe system or a needle-free injection system. Heifers were randomly assigned to control and vaccination gro...

  5. Reassortment of high-yield influenza viruses in vero cells and safety assessment as candidate vaccine strains.

    PubMed

    Zhou, Jian; Yang, Fan; Yang, Jinghui; Ma, Lei; Cun, Yina; Song, Shaohui; Liao, Guoyang

    2017-01-02

    Vaccination is the practiced and accessible measure for preventing influenza infection. Because chicken embryos used for vaccine production have various insufficiencies, more efficient methods are needed. African green monkey kidney (Vero) cells are recommended by the World Health Organization (WHO) as a safe substitute for influenza vaccine production for humans. However, the influenza virus usually had low-yield in Vero cells, which limits the usage of Vero cellular vaccines. This study used 2 high-yield influenza viruses in Vero cells: A/Yunnan/1/2005Va (H3N2) and B/Yunnan/2/2005Va (B) as donor viruses. It used 3 wild strain viruses to reassort new adaptation viruses, including: A/Tianjin/15/2009(H1N1), A/Fujian/196/2009(H3N2), and B/Chongqing/1384/2010(B). These three new viruses could maintain the characteristic of high-yield in Vero cells. Furthermore, they could keep the immunogenic characteristics of the original wild influenza viruses. Importantly, these viruses were shown as safe in chicken embryo and guinea pigs assessment systems. These results provide an alternative method to produce influenza vaccine based on Vero cells.

  6. Cloning and expression of Clostridium perfringens type D vaccine strain epsilon toxin gene in E. coli as a recombinant vaccine candidate

    PubMed Central

    Aziminia, Parastoo; Pilehchian-Langroudi, Reza; Esmaeilnia, Kasra

    2016-01-01

    Background and Objectives: Clostridium perfringens, a Gram-positive obligate anaerobic bacterium, is able to form resistant spores which are widely distributed in the environment. C. perfringens is subdivided into five types A to E based on its four major alpha, beta, epsilon and iota toxins. The aim of the present study was cloning and expression of C. perfringens type D vaccine strain epsilon toxin gene. Materials and Methods: Genomic DNA was extracted and the epsilon toxin gene was amplified using Pfu DNA polymerase. The PCR product was cloned into pJET1.2/blunt cloning vector. The recombinant vector (pJETε) was sequenced using universal primers. At the next step epsilon toxin gene was subcloned into pET22b(+) expression vector and transformed into E. coli Rosetta (DE3) host strain. Results: The recombinant protein has been expressed in E. coli Rosetta (DE3) cells after subcloning of C. perfringens etx gene (1008 bp) into the expression vector. Conclusion: We concluded that E. coli Rosetta strain was suitable for the expression of recombinant C. perfringens epsilon toxin protein from pET22ε expression vector. This recombinant cell can be used for further research on recombinant vaccine development. PMID:28210460

  7. Strain dependent protection conferred by Lactobacillus spp. administered orally with a Salmonella Typhimurium vaccine in a murine challenge model.

    PubMed

    Esvaran, M; Conway, P L

    2012-03-30

    Consumption of Lactobacillus spp. has been shown to enhance immune responses in mice. This study examined the immuno-adjuvant capacity of two strains: Lactobacillus acidophilus L10 and Lactobacillus fermentum PC2, in the induction of protective humoral immunity in a Salmonella Typhimurium vaccine challenge model. Briefly, BALB/c mice were divided into four groups. Three groups of mice received S. Typhimurium vaccine (10(8) colony forming units (CFU) per dose) on days 0 and 14. In addition to the vaccine, five doses (10(8) CFU per dose) of either L. acidophilus L10 or L. fermentum PC2 were also administered to a group. All mice were challenged with viable S. Typhimurium on day 28. On day 10 post challenge, the study was terminated and microbial and immunological parameters were assessed. Mice dosed with L. fermentum PC2 in addition to the vaccine had a significantly enhanced S. Typhimurium humoral response. The mice in this group had high levels of lactobacilli in the feces and in association with the Peyer's patches, no detectable levels of either lactobacilli or S. Typhimurium in the spleen, and no detectable weight loss. Mice given L. acidophilus L10 with the vaccine were unable to exhibit elevated S. Typhimurium specific humoral responses. However, there was no detectable S. Typhimurium in the spleens of this group. Interestingly, translocation of lactobacilli into the spleen was observed as well as a slight weight loss was noted in mice that received the L. acidophilus L10 with the vaccine. This study shows that, the L. fermentum PC2 had a greater capacity than the L. acidophilus L10 to act as an oral adjuvant in a S. Typhimurium oral vaccine program and afforded greater protection against a live S. Typhimurium challenge. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Experience with live attenuated varicella vaccine (Oka strain) in healthy Japanese subjects; 10-year survey at pediatric clinic.

    PubMed

    Ozaki, T; Nishimura, N; Kajita, Y

    2000-05-08

    Live attenuated varicella vaccine (Oka strain, Biken Institute, Osaka, Japan) was administered to 973 healthy individuals over a 10-year period (1987-1997) at the pediatric clinic of Showa Hospital in Japan. We evaluated the relevant serological and clinical data, which were collected by questionnaire. Seroconversion by the immune adherence hemagglutination method was documented in 94% (805/860) of the initially seronegative subjects. Of the initially seropositive subjects, 56% (63/113) showed enhancement of antibody after vaccination. Reactions to the vaccine were generally insignificant, except for a rash at the injection site, seen in the first 3 days post-administration in 17% (41/241) of the recently vaccinated subjects. In March 1998, we conducted a survey of 559 of the initially seronegative subjects who had received the vaccine 0.6-10. 8 (mean 5.4) years earlier. Of these subjects, 21% (119/559) contracted breakthrough varicella. However, their symptoms were milder than those caused by natural varicella seen in unvaccinated children. Seroconversion was demonstrated in 92% (109/119) of these cases. The incidence of breakthrough disease decreased with a rise in postvaccination antibody titer to >==32. Four of the subjects (0.7% of 559) developed herpes zoster following vaccination, two of whom had earlier exhibited breakthrough varicella. Lesions in one case of zoster, without breakthrough varicella, appeared on the cervical dermatome at the injection site. The vaccine was safe and effective. However, there was a relatively high incidence of rash at the injection site with certain lot numbers used in recent years which warrants investigation.

  9. Methyltransferase-defective avian metapneumovirus vaccines provide complete protection against challenge with the homologous Colorado strain and the heterologous Minnesota strain.

    PubMed

    Sun, Jing; Wei, Yongwei; Rauf, Abdul; Zhang, Yu; Ma, Yuanmei; Zhang, Xiaodong; Shilo, Konstantin; Yu, Qingzhong; Saif, Y M; Lu, Xingmeng; Yu, Lian; Li, Jianrong

    2014-11-01

    Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. Since its discovery in the 1970s, aMPV has been recognized as an economically important pathogen in the poultry industry worldwide. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at guanine N-7 (G-N-7) and ribose 2'-O positions. In this study, we generated a panel of recombinant aMPV (raMPV) Colorado strains carrying mutations in the S-adenosyl methionine (SAM) binding site in the CR VI of L protein. These recombinant viruses were specifically defective in ribose 2'-O, but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of specific-pathogen-free (SPF) young turkeys. Importantly, turkeys vaccinated with these MTase-defective raMPVs triggered a high level of neutralizing antibody and were completely protected from challenge with homologous aMPV Colorado strain and heterologous aMPV Minnesota strain. Collectively, our results indicate (i) that aMPV lacking 2'-O methylation is highly attenuated in vitro and in vivo and (ii) that inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for aMPV and perhaps other paramyxoviruses. Paramyxoviruses include many economically and agriculturally important viruses such as avian metapneumovirus (aMPV), and Newcastle disease virus (NDV), human pathogens such as human respiratory syncytial virus, human metapneumovirus, human parainfluenza virus type 3, and measles virus, and highly lethal emerging pathogens such as Nipah virus and Hendra virus. For many of them, there is no effective vaccine or antiviral drug. These viruses share common strategies for viral gene

  10. Identification of a cell epitope that is globally conserved among outer membrane proteins (OMPs) OMP7, OMP8, and OMP9 of anaplasma marginale strains and with OMP7 from the A. marginale subsp. centrale vaccine strain

    USDA-ARS?s Scientific Manuscript database

    Within the protective outer membrane fraction of Anaplasma marginale, several vaccine candidates have emerged, including a family of outer membrane proteins (OMPs) 7-9, which share sequence identity with each other and with the single protein OMP7 in the vaccine strain A. marginale subsp. centrale. ...

  11. Vaccinations

    MedlinePlus

    ... be spread from animals to people. For example, rabies is a serious, often fatal, disease that can ... animals to people. By vaccinating your pets for rabies, you are protecting your family as well as ...

  12. Increased susceptibility of IgA-deficient mice to pulmonary Francisella tularensis live vaccine strain infection.

    PubMed

    Furuya, Yoichi; Kirimanjeswara, Girish S; Roberts, Sean; Metzger, Dennis W

    2013-09-01

    Francisella tularensis, the causative agent of tularemia, is most deadly in the pneumonic form; therefore, mucosal immunity is an important first line of defense against this pathogen. We have now evaluated the lethality of primary F. tularensis live vaccine strain (LVS) pulmonary infection in mice that are defective in IgA (IgA(-/-) mice), the predominant mucosal Ig isotype. The results showed that IgA(-/-) mice were more susceptible than IgA(+/+) mice to intranasal F. tularensis LVS infection, despite developing higher levels of LVS-specific total, IgG, and IgM antibodies in the bronchoalveolar lavage specimens following infection. In addition, the absence of IgA resulted in a significant increase in bacterial loads and reduced survival. Interestingly, IgA(-/-) mice had lower pulmonary gamma interferon (IFN-γ) levels and decreased numbers of IFN-γ-secreting CD4(+) and CD8(+) T cells in the lung on day 9 postinfection compared to IgA(+/+) mice. Furthermore, IgA(-/-) mice displayed reduced interleukin 12 (IL-12) levels at early time points, and supplementing IgA(-/-) mice with IL-12 prior to LVS challenge induced IFN-γ production by NK cells and rescued them from mortality. Thus, IgA(-/-) mice are highly susceptible to primary pulmonary LVS infections not only because of IgA deficiency but also because of reduced IFN-γ responses.

  13. Genetic parameters for resistance to the Salmonella abortusovis vaccinal strain Rv6 in sheep

    PubMed Central

    Moreno, Carole R; Lantier, Frédéric; Berthon, Patricia; Gautier-Bouchardon, Anne V; Boivin, Roger; Lantier, Isabelle; Brunel, Jean-Claude; Weisbecker, Jean-Louis; François, Dominique; Bouix, Jacques; Elsen, Jean-Michel

    2003-01-01

    An experimental population (1216 lambs from 30 sires) of the Inra401 sheep was created in an Inra flock to allow QTL detection for susceptibility to Salmonella infection, wool and carcass traits. The Inra401 is a sheep composite line developed from two breeds: Berrichon du Cher and Romanov. At 113 days of age on average, the lambs were inoculated intravenously with 108 Salmonella abortusovis Rv6 (vaccinal strain). They were slaughtered 10 days after the inoculation. Several traits were measured at inoculation and/or slaughtering to estimate the genetic resistance of the lambs to Salmonella infection: specific IgM and IgG1 antibody titres, body weight loss, spleen and pre-scapular node weights and counts of viable Salmonella persisting in these organs. This paper presents a quantitative analysis of the genetic variability of the traits related to salmonellosis susceptibility. The heritabilities of the traits varied between 0.10 and 0.64 (significantly different from zero). Thus, in sheep as well as in other species, the determinism of resistance to Salmonella infection is under genetic control. Moreover, the correlations between the traits are in agreement with the known immune mechanisms. The genetic variability observed should help QTL detection. PMID:12633533

  14. Measles Edmonston Vaccine Strain Derivatives have Potent Oncolytic Activity against Osteosarcoma

    PubMed Central

    Musibay, Evidio Domingo; Allen, Cory; Kurokawa, Cheyne; Hardcastle, Jayson J.; Aderca, Ileana; Msaouel, Pavlos; Bansal, Aditya; Jiang, Huailei; DeGrado, Timothy R.; Galanis, Evanthia

    2015-01-01

    Osteosarcoma is the most common primary bone tumor affecting children and young adults, and development of metastatic disease is associated with poor prognosis. The purpose of this study was to evaluate the antitumor efficacy of virotherapy with engineered measles virus (MV) vaccine strains in the treatment of osteosarcoma. Cell lines derived from pediatric patients with osteosarcoma (HOS, MG63, 143B, KHOS-312H, U2-OS and SJSA1) were examined for MV-GFP and MV-NIS gene expression and cytotoxicity as defined by syncytial formation, cell death, and eradication of cell monolayers: significant antitumor activity was demonstrated. Findings were correlated with in vivo efficacy in subcutaneous, orthotopic (tibial bone), and lung metastatic osteosarcoma xenografts treated with the MV derivative MV-NIS via the intratumoral (IT) or intravenous (IV) route. Following treatment, we observed decrease in tumor growth of subcutaneous xenografts (p=0.0374) and prolongation of survival in mice with orthotopic (p<0.0001) and pulmonary metastatic osteosarcoma tumors (p=0.0207). Expression of the NIS transgene in MV-NIS infected tumors allowed for SPECT-CT and PET-CT imaging of virus infected tumors in vivo. Our data support the translational potential of MV-based virotherapy approaches in the treatment of recurrent and metastatic osteosarcoma. PMID:25394505

  15. A Killed, Genetically Engineered Derivative of a Wild-Type Extraintestinal Pathogenic E. coli strain is a Vaccine Candidate

    PubMed Central

    Russo, Thomas A.; Beanan, Janet M.; Olson, Ruth; Genagon, Stacy A.; MacDonald, Ulrike; Cope, John J.; Davidson, Bruce A.; Johnston, Brian; Johnson, James R.

    2007-01-01

    Infections due to extraintestinal pathogenic E. coli (ExPEC) result in significant morbidity, mortality and increased healthcare costs. An efficacious vaccine against ExPEC would be desirable. In this report we explore the use of killed-whole E. coli as a vaccine immunogen. Given the diversity of capsule and O-antigens in ExPEC we have hypothesized that alternative targets are viable vaccine candidates. We have also hypothesized that immunization with a genetically engineered strain that is deficient in the capsule and O-antigen will generate a greater immune response against antigens other than the capsular and O-antigen epitopes than a wild-type strain. Lastly, we hypothesize that mucosal immunization with killed E. coli has the potential to generate a significant immune response. In this study we demonstrated that nasal immunization with a formalin-killed ExPEC derivative deficient in capsule and O-antigen results in a significantly greater overall humoral response compared to its wild-type derivative (which demonstrates that capsule and/or the O-antigen impede the development of an optimal humoral immune response) and a significantly greater immune response against non-capsular and O-antigen epitopes. These antibodies also bound to a subset of heterologous ExPEC strains and enhanced neutrophil-mediated bactericidal activity against the homologous and a heterologous strain. Taken together these studies support the concept that formalin-killed genetically engineered ExPEC derivatives are whole cell vaccine candidates to prevent infections due to ExPEC. PMID:17306426

  16. Vaccination of pigs with the S48 strain of Toxoplasma gondii--safer meat for human consumption.

    PubMed

    Burrells, Alison; Benavides, Julio; Cantón, German; Garcia, João L; Bartley, Paul M; Nath, Mintu; Thomson, Jackie; Chianini, Francesca; Innes, Elisabeth A; Katzer, Frank

    2015-05-01

    As clinical toxoplasmosis is not considered a problem in pigs, the main reason to implement a control strategy against Toxoplasma gondii (T. gondii) in this species is to reduce the establishment of T. gondii tissue cysts in pork, consequently reducing the risk of the parasite entering the human food chain. Consumption of T. gondii tissue cysts from raw or undercooked meat is one of the main sources of human infection, with infected pork being considered a high risk. This study incorporates a mouse bioassay with molecular detection of T. gondii DNA to study the effectiveness of vaccination (incomplete S48 strain) in its ability to reduce tissue cyst burden in pigs, following oocyst (M4 strain) challenge. Results from the mouse bioassay show that 100% of mice which had received porcine tissues from vaccinated and challenged pigs survived compared with 51.1% of mice which received tissues from non-vaccinated and challenged pigs. The presence (or absence) of T. gondii DNA from individual mouse brains also confirmed these results. This indicates a reduction in viable T. gondii tissue cysts within tissues from pigs which have been previously vaccinated with the S48 strain. In addition, the study demonstrated that the main predilection sites for the parasite were found to be brain and highly vascular muscles (such as tongue, diaphragm, heart and masseter) of pigs, while meat cuts used as human food such as chop, loin, left tricep and left semitendinosus, had a lower burden of T. gondii tissue cysts. These promising results highlight the potential of S48 strain tachyzoites for reducing the number of T. gondii tissues cysts in pork and thus improving food safety.

  17. Genetic Determinants of Japanese Encephalitis Virus Vaccine Strain SA14-14-2 That Govern Attenuation of Virulence in Mice.

    PubMed

    Gromowski, Gregory D; Firestone, Cai-Yen; Whitehead, Stephen S

    2015-06-01

    The safety and efficacy of the live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine are attributed to mutations that accumulated in the viral genome during its derivation. However, little is known about the contribution that is made by most of these mutations to virulence attenuation and vaccine immunogenicity. Here, we generated recombinant JEV (rJEV) strains containing JEV SA14-14-2 vaccine-specific mutations that are located in the untranslated regions (UTRs) and seven protein genes or are introduced from PCR-amplified regions of the JEV SA14-14-2 genome. The resulting mutant viruses were evaluated in tissue culture and in mice. The authentic JEV SA14-14-2 (E) protein, with amino acid substitutions L107F, E138K, I176V, T177A, E244G, Q264H, K279M, A315V, S366A, and K439R relative to the wild-type rJEV clone, was essential and sufficient for complete attenuation of neurovirulence. Individually, the nucleotide substitution T39A in the 5' UTR (5'-UTR-T39A), the capsid (C) protein amino acid substitution L66S (C-L66S), and the complete NS1/2A genome region containing 10 mutations each significantly reduced virus neuroinvasion but not neurovirulence. The levels of peripheral virulence attenuation imposed by the 5'-UTR-T39A and C-L66S mutations, individually, were somewhat mitigated in combination with other vaccine strain-specific mutations, which might be compensatory, and together did not affect immunogenicity. However, a marked reduction in immunogenicity was observed with the addition of the NS1/2A and NS5 vaccine virus genome regions. These results suggest that a second-generation recombinant vaccine can be rationally engineered to maximize levels of immunogenicity without compromising safety. The live-attenuated JEV SA14-14-2 vaccine has been vital for controlling the incidence of disease caused by JEV, particularly in rural areas of Asia where it is endemic. The vaccine was developed >25 years ago by passaging wild-type JEV strain SA14 in tissue

  18. Difference in cultivation characteristics and genetic polymorphism between Chinese and Japanese strains of Wolfiporia cocos Ryvarden et Gilbertson (Poria cocos Wolf).

    PubMed

    Kobira, Sayuri; Atsumi, Toshiyuki; Kakiuchi, Nobuko; Mikage, Masayuki

    2012-07-01

    Poria, a dried sclerotium of Wolfiporia cocos Ryvarden et Gilbertson (Polyporaceae) has been used as a crude drug in both Chinese and Japanese (Kampo) traditional medicines. Recently, cultivated products of Chinese Poria strains have accounted for most of the market, while the cultivation of Japanese Poria strains has not been successful. Aiming to determine the relationship between the differences in cultivation characteristics and genetic polymorphism, we conducted a field cultivation experiment, a rot test, and rapid amplification of polymorphic DNA (RAPD) analysis of Poria strains collected from China and Japan: 3 Chinese and 7 Japanese strains. In field cultivation, although there was no marked inferiority of Japanese strains to Chinese ones in either mycelium propagation or the rate of sclerotium formation, Chinese strains formed whiter sclerotia with a mean size more than twice that of Japanese ones. Representatives of Chinese and Japanese strains, Yunnan and Kaimondake, respectively, were tested for wood-rotting ability. More wood was utilized and the wood color was darker in trials of the Yunnan strain. Amplifications of total DNA of these 10 fungal strains with 2 primers, PC-6 and PC-11, in RAPD analysis showed a difference in the amplicon profile between Japanese and Chinese strains, suggesting differences in their genetic background.

  19. Comparative analyses of the 9 glycoprotein genes found in wild-type and vaccine strains of varicella-zoster virus.

    PubMed

    Storlie, Johnathan; Maresova, Lucie; Jackson, Wallen; Grose, Charles

    2008-03-01

    The complete DNA sequences of wild-type and vaccine strains of varicella-zoster virus have been published and listed in GenBank. In this comparative genomic analysis, the sequences of the 9 glycoprotein open reading frames (ORFs) were compared. They included gE (ORF68), gI (ORF 67), gC (ORF14), gH (ORF37), gL (ORF60), gB (ORF31), gK (ORF5), gM (ORF50), and gN (ORF8 or ORF9A). After realignment on the basis of newer data, the corrected gB sequence was lengthened to include 931 residues. The data showed that there were glycoprotein polymorphisms that differentiated North American/European strains from Japanese strains-for example, an additional ATG codon in the gL of all Oka strains. Also, there were a small number of coding single-nucleotide polymorphisms present only in glycoproteins of vaccine strains. Because these changes were highly conserved, the structure of the glycoprotein was unlikely to be altered.

  20. Genetic variations of live attenuated plague vaccine strains (Yersinia pestis EV76 lineage) during laboratory passages in different countries.

    PubMed

    Cui, Yujun; Yang, Xianwei; Xiao, Xiao; Anisimov, Andrey P; Li, Dongfang; Yan, Yanfeng; Zhou, Dongsheng; Rajerison, Minoarisoa; Carniel, Elisabeth; Achtman, Mark; Yang, Ruifu; Song, Yajun

    2014-08-01

    Plague, one of the most devastating infectious diseases in human history, is caused by the bacterial species Yersinia pestis. A live attenuated Y. pestis strain (EV76) has been widely used as a plague vaccine in various countries around the world. Here we compared the whole genome sequence of an EV76 strain used in China (EV76-CN) with the genomes of Y. pestis wild isolates to identify genetic variations specific to the EV76 lineage. We identified 6 SNPs and 6 Indels (insertions and deletions) differentiating EV76-CN from its counterparts. Then, we screened these polymorphic sites in 28 other strains of EV76 lineage that were stored in different countries. Based on the profiles of SNPs and Indels, we reconstructed the parsimonious dissemination history of EV76 lineage. This analysis revealed that there have been at least three independent imports of EV76 strains into China. Additionally, we observed that the pyrE gene is a mutation hotspot in EV76 lineages. The fine comparison results based on whole genome sequence in this study provide better understanding of the effects of laboratory passages on the accumulation of genetic polymorphisms in plague vaccine strains. These variations identified here will also be helpful in discriminating different EV76 derivatives. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Genetic and antigenic analysis of H5N1 viruses for selection of HA-donor virus for vaccine strains.

    PubMed

    Bhatia, S; Kunal, A; Khandia, R; Siddiqui, A; Pateriya, A K; Sood, R

    2013-12-01

    Genetic and antigenic analysis of H5N1 viruses, isolated in India during a period from year 2006 to 2010, was carried out for selection of the potential H5-HA (haemagglutinin) gene donor virus for developing a reverse genetics based DIVA marker H5 vaccine for poultry in India. Out of the 47 H5N1 viruses (clade 2.2), 14 representative viruses were selected on the basis of amino acid sequence analysis of HA1 gene for further antigenic characterization. Using antigenic cartography, an antigenic map was constructed based on the data of cross-HI (haemagglutinin inhibition) titration of 14 sera versus 14 viruses to visualize the relatedness among the antigens and antigenic coverage of the sera. Sera against five H5N1 viruses (A/crow/Assam/142119/2008, A/chicken/West Bengal/100879/2008, A/chicken/West Bengal/155505/2009, A/chicken/West Bengal/80995/2008 and A/chicken/West Bengal/81760/2008) exhibited maximum (100 %) antigenic coverage, hence, were selected as the potential HA donor viruses. However, the virus strain A/chicken/West Bengal/80995/2008 matched completely with the consensus amino acid sequence of the 47 viruses, therefore, was considered the best HA donor candidate out of the five showing 100 % antigenic coverage. The present study demonstrates a stepwise methodology for logical selection of vaccine strain or HA gene donor strain for developing H5 vaccines using genetic and antigenic data.

  2. Development and evaluation of an experimental vaccination program using a live avirulent Salmonella typhimurium strain to protect immunized chickens against challenge with homologous and heterologous Salmonella serotypes.

    PubMed Central

    Hassan, J O; Curtiss, R

    1994-01-01

    A stable live avirulent, genetically modified delta cya delta crp Salmonella typhimurium vaccine strain, chi 3985, was used in several vaccination strategies to evaluate its use in the control of Salmonella infection in chickens. Oral vaccination of chickens at 1 and at 14 days of age with 10(8) CFU of chi 3985 protected against invasion of spleen, ovary, and bursa of Fabricius and colonization of the ileum and cecum in chickens challenged with 10(6) CFU of virulent homologous Salmonella strains from group B. Chickens challenged with heterologous Salmonella strains from groups C, D, and E were protected against visceral invasion of spleen and ovary, while invasion of the bursa of Fabricius and colonization of ileum and cecum was reduced in vaccinated chickens. Oral vaccination at 2 and at 4 weeks of age induced an excellent protection against challenge with virulent group B Salmonella serotypes and very good protection against challenge with group D or E Salmonella serotypes, while protection against challenge with group C Salmonella serotypes was marginal but significant. Vaccination at 2 and at 4 weeks of age also protected vaccinated chickens against challenge with 10(8) CFU of highly invasive S. typhimurium or S. enteritidis strains. The protection of chickens vaccinated with chi 3985 against challenge with homologous and heterologous Salmonella serotypes is outstanding, and the complete protection against ovarian invasion in chickens challenged with 10(8) CFU of highly invasive S. typhimurium or S. enteritidis strains suggests that vaccination of chickens with chi 3985 can complement the present hygiene- and sanitation-based Salmonella control measures. This paper reports a breakthrough in the use of live avirulent vaccine to control Salmonella carriers in chickens. PMID:7960134

  3. Real-time RT-PCR assays to differentiate wild-type group A rotavirus strains from Rotarix(®) and RotaTeq(®) vaccine strains in stool samples.

    PubMed

    Gautam, Rashi; Esona, Mathew D; Mijatovic-Rustempasic, Slavica; Ian Tam, Ka; Gentsch, Jon R; Bowen, Michael D

    2014-01-01

    Group A rotaviruses (RVA) are the leading cause of severe diarrhea in young children worldwide. Two live-attenuated RVA vaccines, Rotarix(®) and RotaTeq(®) are recommended by World Health Organization (WHO) for routine immunization of all infants. Rotarix(®) and RotaTeq(®) vaccines have substantially reduced RVA associated mortality but occasionally have been associated with acute gastroenteritis (AGE) cases identified in vaccinees and their contacts. High-throughput assays are needed to monitor the prevalence of vaccine strains in AGE cases and emergence of new vaccine-derived strains following RVA vaccine introduction. In this study, we have developed quantitative real-time RT-PCR (qRT-PCR) assays for detection of Rotarix(®) and RotaTeq(®) vaccine components in stool samples. Real-time RT-PCR assays were designed for vaccine specific targets in the genomes of Rotarix(®) (NSP2, VP4) and RotaTeq(®) (VP6, VP3-WC3, VP3-human) and validated on sequence confirmed stool samples containing vaccine strains, wild-type RVA strains, and RVA-negative stools. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Rotarix(®) NSP2 and VP4 qRT-PCR assays exhibited 92-100% sensitivity, 99-100% specificity, 94-105% efficiency, and a limit of detection of 2-3 copies per reaction. RotaTeq(®) VP6, VP3-WC3, and VP3-human qRT-PCR assays displayed 100% sensitivity, 94-100% specificity, 91-102% efficiency and limits of detection of 1 copy, 2 copies, and 140 copies, respectively. These assays permit rapid identification of Rotarix(®) and RotaTeq(®) vaccine components in stool samples from clinical and surveillance studies and will be helpful in determining the frequency of vaccine strain-associated AGE.

  4. Identification of a T-Cell Epitope That Is Globally Conserved among Outer Membrane Proteins (OMPs) OMP7, OMP8, and OMP9 of Anaplasma marginale Strains and with OMP7 from the A. marginale subsp. centrale Vaccine Strain

    PubMed Central

    Deringer, James R.; Forero-Becerra, Elkin G.; Ueti, Massaro W.; Turse, Joshua E.; Futse, James E.; Noh, Susan M.; Palmer, Guy H.

    2016-01-01

    ABSTRACT Within the protective outer membrane (OM) fraction of Anaplasma marginale, several vaccine candidates have emerged, including a family of OM proteins (OMPs) 7 to 9, which share sequence identity with each other and with the single protein OMP7 in the vaccine strain A. marginale subsp. centrale. A. marginale OMPs 7 to 9 are logical vaccine candidates because they are surface exposed, present in the OM immunogen and protective cross-linked OM proteins, recognized by immune serum IgG2 and T cells in cattle immunized with OM, and recognized by immune serum IgG2 from cattle immunized with the A. centrale vaccine strain. We report the identification of a globally conserved 9-amino-acid T-cell epitope FLLVDDAI/VV shared between A. centrale vaccine strain OMP7 and the related A. marginale OMPs 7 to 9, where position 8 of the peptide can be isoleucine or valine. The epitope is conserved in American A. marginale strains, in the Australia Gypsy Plains strain, and in multiple field isolates from Ghana. This epitope, together with additional T-cell epitopes that are present within these proteins, should be considered for inclusion in a multivalent vaccine for A. marginale that can provide protection against disease caused by globally distributed bacterial strains. PMID:27795302

  5. Detection of Mycoplasma mycoides subsp. mycoides SC in bronchoalveolar lavage fluids of cows based on a TaqMan real-time PCR discriminating wild type strains from an lppQ− mutant vaccine strain used for DIVA-strategies

    PubMed Central

    Vilei, Edy M.; Frey, Joachim

    2010-01-01

    Contagious bovine pleuropneumonia (CBPP) is the most serious cattle disease in Africa, caused by Mycoplasma mycoides subsp. mycoides small-colony type (SC). CBPP control strategies currently rely on vaccination with a vaccine based on live attenuated strains of the organism. Recently, an lppQ− mutant of the existing vaccine strain T1/44 has been developed (Janis et al., 2008). This T1lppQ− mutant strain is devoid of lipoprotein LppQ, a potential virulence attribute of M. mycoides subsp. mycoides SC. It is designated as a potential live DIVA (Differentiating Infected from Vaccinated Animals) vaccine strain allowing both serological and etiological differentiation. The present paper reports on the validation of a control strategy for CBPP in cattle, whereby a TaqMan real-time PCR based on the lppQ gene has been developed for the direct detection of M. mycoides subsp. mycoides SC in ex vivo bronchoalveolar lavage fluids of cows and for the discrimination of wild type strains from the lppQ− mutant vaccine strain. PMID:20381545

  6. Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus

    PubMed Central

    Medaglia, Maria Luiza G.; Moussatché, Nissin; Nitsche, Andreas; Dabrowski, Pjotr Wojtek; Li, Yu; Damon, Inger K.; Lucas, Carolina G. O.; Arruda, Luciana B.

    2015-01-01

    ABSTRACT Smallpox was declared eradicated in 1980 after an intensive vaccination program using different strains of vaccinia virus (VACV; Poxviridae). VACV strain IOC (VACV-IOC) was the seed strain of the smallpox vaccine manufactured by the major vaccine producer in Brazil during the smallpox eradication program. However, little is known about the biological and immunological features as well as the phylogenetic relationships of this first-generation vaccine. In this work, we present a comprehensive characterization of two clones of VACV-IOC. Both clones had low virulence in infected mice and induced a protective immune response against a lethal infection comparable to the response of the licensed vaccine ACAM2000 and the parental strain VACV-IOC. Full-genome sequencing revealed the presence of several fragmented virulence genes that probably are nonfunctional, e.g., F1L, B13R, C10L, K3L, and C3L. Most notably, phylogenetic inference supported by the structural analysis of the genome ends provides evidence of a novel, independent cluster in VACV phylogeny formed by VACV-IOC, the Brazilian field strains Cantagalo (CTGV) and Serro 2 viruses, and horsepox virus, a VACV-like virus supposedly related to an ancestor of the VACV lineage. Our data strongly support the hypothesis that CTGV-like viruses represent feral VACV that evolved in parallel with VACV-IOC after splitting from a most recent common ancestor, probably an ancient smallpox vaccine strain related to horsepox virus. Our data, together with an interesting historical investigation, revisit the origins of VACV and propose new evolutionary relationships between ancient and extant VACV strains, mainly horsepox virus, VACV-IOC/CTGV-like viruses, and Dryvax strain. IMPORTANCE First-generation vaccines used to eradicate smallpox had rates of adverse effects that are not acceptable by current health care standards. Moreover, these vaccines are genetically heterogeneous and consist of a pool of quasispecies of VACV

  7. Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus.

    PubMed

    Medaglia, Maria Luiza G; Moussatché, Nissin; Nitsche, Andreas; Dabrowski, Pjotr Wojtek; Li, Yu; Damon, Inger K; Lucas, Carolina G O; Arruda, Luciana B; Damaso, Clarissa R

    2015-12-01

    Smallpox was declared eradicated in 1980 after an intensive vaccination program using different strains of vaccinia virus (VACV; Poxviridae). VACV strain IOC (VACV-IOC) was the seed strain of the smallpox vaccine manufactured by the major vaccine producer in Brazil during the smallpox eradication program. However, little is known about the biological and immunological features as well as the phylogenetic relationships of this first-generation vaccine. In this work, we present a comprehensive characterization of two clones of VACV-IOC. Both clones had low virulence in infected mice and induced a protective immune response against a lethal infection comparable to the response of the licensed vaccine ACAM2000 and the parental strain VACV-IOC. Full-genome sequencing revealed the presence of several fragmented virulence genes that probably are nonfunctional, e.g., F1L, B13R, C10L, K3L, and C3L. Most notably, phylogenetic inference supported by the structural analysis of the genome ends provides evidence of a novel, independent cluster in VACV phylogeny formed by VACV-IOC, the Brazilian field strains Cantagalo (CTGV) and Serro 2 viruses, and horsepox virus, a VACV-like virus supposedly related to an ancestor of the VACV lineage. Our data strongly support the hypothesis that CTGV-like viruses represent feral VACV that evolved in parallel with VACV-IOC after splitting from a most recent common ancestor, probably an ancient smallpox vaccine strain related to horsepox virus. Our data, together with an interesting historical investigation, revisit the origins of VACV and propose new evolutionary relationships between ancient and extant VACV strains, mainly horsepox virus, VACV-IOC/CTGV-like viruses, and Dryvax strain. First-generation vaccines used to eradicate smallpox had rates of adverse effects that are not acceptable by current health care standards. Moreover, these vaccines are genetically heterogeneous and consist of a pool of quasispecies of VACV. Therefore, the

  8. Experimental infection of nontarget species of rodents and birds with Brucella abortus strain RB51 vaccine

    USGS Publications Warehouse

    Januszewski, M.C.; Olsen, S.C.; McLean, R.G.; Clark, L.; Rhyan, Jack C.

    2001-01-01

    The Brucella abortus vaccine strain RB51 (SRB51) is being considered for use in the management of bnucellosis in wild bison (Bison bison) and elk (Cervus elaphus) populations in the Greater Yellowstone Area (USA). Evaluation of the vaccines safety in non-target species was considered necessary prior to field use. Between June 1998 and December 1999, ground squirrels (Spermophilus richardsonii, n = 21), deer mice (Peromyscus maniculatus, n = 14), prairie voles (Microtus ochrogaster, n = 21), and ravens (Corvus corax, n = 13) were orally inoculated with SRB51 or physiologic saline. Oral and rectal swabs and blood samples were collected for bacteriologic evaluation. Rodents were necropsied at 8 to 10 wk and 12 to 21 wk post inoculation (PI), and ravens at 7 and 11 wk PI. Spleen, liver and reproductive tissues were collected for bacteriologic and histopathologic evaluation. No differences in clinical signs, appetite, weight loss or gain, or activity were observed between saline- and SRB51-inoculated animals in all four species. Oral and rectal swabs from all species were negative throughout the study. In tissues obtained from SRB51-inoculated animals, the organism was isolated from six of seven (86%) ground squirrels, one of six (17%) deer mice, none of seven voles, and one of five (20%) ravens necropsied at 8, 8, 10, and 7 wk PI, respectively. Tissues from four of seven (57%) SRB51-inoculated ground squirrels were culture positive for the organism 12 wk PI; SRB51 was not recovered from deer mice, voles. or ravens necropsied 12, 21, or 11 wk, respectively, PI. SRB51 was not recovered from saline-inoculated ground squirrels, deer mice, or voles at any time but was recovered from one saline-inoculated raven at necropsy, 7 wk PI, likely attributable to contact with SRB51-inoculated ravens in an adjacent aviary room. Spleen was time primary tissue site of colonization in ground squirrels, followed by the liver and reproductive organs. The results indicate oral exposure to

  9. Durability of immunogenicity and strain coverage of MenBvac, a meningococcal vaccine based on outer membrane vesicles: Lessons of the Normandy campaign.

    PubMed

    Sevestre, Julien; Hong, Eva; Delbos, Valérie; Terrade, Aude; Mallet, Eric; Deghmane, Ala-Eddine; Lemée, Ludovic; Taha, Muhamed-Kheir; Caron, François

    2017-07-13

    MenBvac® is an outer membrane vesicle (OMV)-based meningococcal vaccine. From 2006 to 2012, it was used to control a clonal B outbreak in Normandy (France). We aimed to analyse the durability of the response against the epidemic strain and coverage beyond the vaccine strain. These data should help to optimize the use of OMV-containing vaccines, such as the new 4CMenB/Bexsero® recombinant vaccine. Serum bactericidal activity (SBA) was measured in two cohorts of children who received their first dose of MenBvac® at 1-5years of age and accepted to provide a blood sample either one or four years after a 2+1+1 schedule. All sera were tested against the outbreak strain. Sera from responder subjects were also tested against 12 additional B or C strains which were chosen to entirely, partially, or not at all match the two variable regions (VR1 and VR2) of the PorA vaccine strain. Only 47.9% and 31.3% of subjects showed an SBA titre consistent with protection one and four years, respectively, after the last boost. Protective SBA titres were observed in all sera against B or C strains that entirely matched P1.7,16, and was high (75-100%) for all but one strain that partially matched VR1 or VR2. Extrapolating our data to the OMV component of 4CMenB/Bexsero® suggests that 14.5% of the current B strains would be covered based on PorA matching to the OMV component of 4CMenB/Bexsero® (regardless of the coverage of the three other vaccine components). Our data confirm that OMV-based vaccines elicit short-lasting SBA titres and may require repeated booster injections. However, strain coverage may be greater than expected. Copyright © 2017. Published by Elsevier Ltd.

  10. A novel dengue virus serotype 1 vaccine candidate based on Japanese encephalitis virus vaccine strain SA14-14-2 as the backbone.

    PubMed

    Yang, Huiqiang; Li, Zhushi; Lin, Hua; Wang, Wei; Yang, Jian; Liu, Lina; Zeng, Xianwu; Wu, Yonglin; Yu, Yongxin; Li, Yuhua

    2016-06-01

    To develop a potential dengue vaccine candidate, a full-length cDNA clone of a novel chimeric virus was constructed using recombinant DNA technology, with Japanese encephalitis virus (JEV) vaccine strain SA14-14-2 as the backbone, with its premembrane (prM) and envelope (E) genes substituted by their counterparts from dengue virus type 1 (DENV1). The chimeric virus (JEV/DENV1) was successfully recovered from primary hamster kidney (PHK) cells by transfection with the in vitro transcription products of JEV/DENV1 cDNA and was identified by complete genome sequencing and immunofluorescent staining. No neuroinvasiveness of this chimeric virus was observed in mice inoculated by the subcutaneous route (s.c.) or by the intraperitoneal route (i.p.), while some neurovirulence was displayed in mice that were inoculated directly by the intracerebral route (i.c.). The chimeric virus was able to stimulate high-titer production of antibodies against DENV1 and provided protection against lethal challenge with neuroadapted dengue virus in mice. These results suggest that the chimeric virus is a promising dengue vaccine candidate.

  11. Cross-protective efficacy of engineering serotype A foot-and-mouth disease virus vaccine against the two pandemic strains in swine.

    PubMed

    Zheng, Haixue; Lian, Kaiqi; Yang, Fan; Jin, Ye; Zhu, Zixiang; Guo, Jianhong; Cao, Weijun; Liu, Huanan; He, Jijun; Zhang, Keshan; Li, Dan; Liu, Xiangtao

    2015-10-26

    Foot-and-mouth disease (FMD) is a highly contagious vesicular disease that affects domestic and wild cloven-hoofed animals worldwide. Recently, a series of outbreaks of type A FMDV occurred in Southeast Asian countries, China, the Russia Federation, Mongolia, Kazakhstan and South Korea. The FMD virus (A/GDMM/CHA/2013) from China's Guangdong province (2013) is representative of those responsible for the latest epidemic, and has low amino acid identity (93.9%) in VP1 protein with the epidemic strain A/WH/CHA/09 from Wuhan, China in 2009. Both of isolates belong to the Sea-97 genotype of ASIA topotype. Therefore, the application of a new vaccine strain with cross-protective efficacy is of fundamental importance to control the spread of the two described pandemic strains. A chimeric strain rA/P1-FMDV constructed by our lab previously through replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09, has been demonstrated to exhibit good growth characteristics in culture, and the rA/P1-FMDV inactivated vaccine can provide protection against epidemic strain A/WH/CHA/09 in cattle. However, it is still unclear whether the vaccine produces efficient protection against the new pandemic strain (A/GDMM/CHA/2013). Here, vaccine matching and pig 50% protective dose (PD50) tests were performed to assess the vaccine potency. The vaccine matching test showed cross-reactivity of sera from full dose vaccine vaccinated pigs with A/WH/CHA/09 and A/GDMM/CHA/2013 isolates, with average r1 values of 0.94±0.12 and 0.68±0.06 (r1≥0.3), which indicates that the rA/P1-FMDV vaccine is likely to confer good cross-protection against the two isolates. When challenged with two pandemic isolates A/WH/CHA/09 and A/GDMM/CHA/2013 strain, the vaccine achieved 12.51 PD50 and 10.05 PD50 per dose (2.8μg), respectively. The results indicated that the rA/P1-FMDV inactivated vaccine could protect pigs against both A/WH/CHA/09 and A/GDMM/CHA/2013 pandem