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

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

PubMed Central

Kaneko, Mei; 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

Genetic heterogeneity of L-Zagreb mumps virus vaccine strain

PubMed Central

Kosutic-Gulija, Tanja; Forcic, Dubravko; Šantak, Maja; Ramljak, Ana; Mateljak-Lukacevic, Sanja; Mazuran, Renata

2008-01-01

Background The most often used mumps vaccine strains Jeryl Lynn (JL), RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. Results We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s) and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. Conclusion L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes. PMID:18616793

Phylogenetic analysis of Hungarian goose parvovirus isolates and vaccine strains.

PubMed

Tatár-Kis, Tímea; Mató, Tamás; Markos, Béla; Palya, Vilmos

2004-08-01

Polymerase chain reaction and sequencing were used to analyse goose parvovirus field isolates and vaccine strains. Two fragments of the genome were amplified. Fragment "A" represents a region of VP3 gene, while fragment "B" represents a region upstream of the VP3 gene, encompassing part of the VP1 gene. In the region of fragment "A" the deduced amino acid sequence of the strains was identical, therefore differentiation among strains could be done only at the nucleotide level, which resulted in the formation of three groups: Hungarian, West-European and Asian strains. In the region of fragment "B", separation of groups could be done by both nucleotide and deduced amino acid sequence level. The nucleotide sequences resulted in the same groups as for fragment "A" but with a different clustering pattern among the Hungarian strains. Within the "Hungarian" group most of the recent field isolates fell into one cluster, very closely related or identical to each other, indicating a very slow evolutionary change. The attenuated strains and field isolates from 1979/80 formed a separate cluster. When vaccine strains and field isolates were compared, two specific amino acid differences were found that can be considered as possible markers for vaccinal strains. Sequence analysis of fragment "B" seems to be a suitable method for differentiation of attenuated vaccine strains from virulent strains. Copyright 2004 Houghton Trust Ltd

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.

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.

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. Copyright © 2010 Elsevier Ltd. All rights reserved.

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 R 2 B (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 log 2 haemagglutination inhibition (HI) units, compared to a GMT of 6.0 log 2 HI units following booster vaccination with R 2 B 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.

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.

Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses identified during vaccine trial in Africa.

PubMed

Heylen, Elisabeth; Zeller, Mark; Ciarlet, Max; Lawrence, Jody; Steele, Duncan; Van Ranst, Marc; Matthijnssens, Jelle

2015-10-06

RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes. During clinical trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year follow-up was lower against the genotypes contained in the vaccine than against the heterotypic G8P[6] and G8P[1] rotavirus strains of which the former is highly prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa, were conducted to gain insight into the high level of cross-protection afforded by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the presence of a high number of bovine rotavirus gene segments in these human G8 strains. In addition, we performed an in depth analysis on the individual amino acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone. Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.

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 ...

Strain-specific reverse transcriptase PCR assay: means to distinguish candidate vaccine from wild-type strains of respiratory syncytial virus.

PubMed Central

Zheng, H; Peret, T C; Randolph, V B; Crowley, J C; Anderson, L J

1996-01-01

Candidate live-virus vaccines for respiratory syncytial virus are being developed and are beginning to be evaluated in clinical trials. To distinguish candidate vaccine strains from wild-type strains isolated during these trials, we developed PCR assays specific to two sets of candidate vaccine strains. The two sets were a group A strain (3A), its three attenuated, temperature-sensitive variant strains, a group B strain (2B), and its four attenuated, temperature-sensitive variant strains. The PCR assays were evaluated by testing 18 group A wild-type strains, the 3A strains, 9 group B wild-type strains, and the 2B strains. PCR specific to group A wild-type strains amplified only group A wild-type strains, and 3A-specific PCR amplified only 3A strains. PCR specific to group B wild-type strains amplified all group A and group B strains but gave a 688-bp product for group B wild-type strains, a 279-bp product for 2B strains, a 547-bp product for all group A strains, and an additional 688-bp product for some group A strains, including 3A strains. These types of PCR assays can, in conjunction with other methods, be used to efficiently distinguish candidate vaccine strains from other respiratory syncytial virus strains. PMID:8789010

A wide extent of inter-strain diversity in virulent and vaccine strains of alphaherpesviruses.

PubMed

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

2011-10-01

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

Rotavirus A genotype G1P[8]: a novel method to distinguish wild-type strains from the Rotarix vaccine strain.

PubMed

Rose, Tatiana L; Miagostovich, Marize P; Leite, José Paulo G

2010-12-01

Rotaviruses are important enteric pathogens for humans and animals. Group A rotaviruses (RV-A) are the most common agents of severe gastroenteritis in infants and young children and vaccination is the most effective method to reduce RV-A-associated diseases. G1P[8], the most prevalent RV-A genotype worldwide, is included in the RV-A vaccine Rotarix®. The discrimination between wild-type G1P[8] and vaccine G1P[8] strains is an important topic in the study of RV-A epidemiology to manage outbreaks and to define control measures for vaccinated children. In this study, we developed a novel method to segregate the wild-type and vaccine strains using restriction endonucleases. The dsRNA from the Rotarix® vaccine was sequenced and the NSP3 gene was selected as the target gene. The vaccine strain has a restriction pattern that is different than that of wild-type RV-A G1P[8] isolates after digestion with the restriction endonuclease BspHI. This pattern could be used as a marker for the differentiation of wild-type G1P[8] strains from the vaccine strain.

Lack of effect of a booster dose of influenza vaccine in hemodialysis patients.

PubMed

Tanzi, Elisabetta; Amendola, Antonella; Pariani, Elena; Zappa, Alessandra; Colzani, Daniela; Logias, Franco; Perego, Angelo; Zanetti, Alessandro R

2007-08-01

To assess whether the administration of a booster dose of influenza vaccine may enhance immune response in hemodialysis patients, 58 subjects were given two doses of the 2003/2004 season influenza vaccine, 1 month apart. "European Agency for the Evaluation of Medicinal Products" (EMEA) criteria were fully met in terms of percentage of response and of mean-fold increase of hemagglutination inhibiting (HI) antibody titer, but not in terms of seroprotection rates (HI antibody titers > or =1:40). The second vaccine administration did not result in additional increase in seroprotection rate or in geometric mean titers. Protective immune response against the epidemic A/H3N2 Fujian-like strain, antigenically distant from that included in the vaccine (A/Panama/2007/99) was observed in 94.7% of vaccinees protected against the A/H3N2 vaccine strain 1 month after immunization. No adverse reactions were reported during follow-up. The study findings suggest that immune response to influenza vaccination may be suboptimal in hemodialysis patients and that the administration of an additional second dose of vaccine does not improve the humoral response.

Are vaccine strain, type or administration protocol risk factors for canine parvovirus vaccine failure?

PubMed

Altman, K D; Kelman, M; Ward, M P

2017-10-01

Canine parvovirus (CPV) is a highly contagious and worldwide cause of serious and often fatal disease in dogs, despite the widespread availability of vaccines. Which vaccine-related factors are associated with vaccination failure is largely unknown, and there are no reports from Australia. In this study - the first national population-level CPV study of its kind ever conducted - we analysed data on 594 cases of apparent CPV vaccination failure reported from an Australian national surveillance system to determine whether vaccine strain, type or administration protocol are risk factors for vaccination failures. The strain of CPV used in vaccine manufacture was not significantly associated with vaccination failure in clinical practice. The vaccine type (killed versus attenuated vaccine) for puppies diagnosed with CPV was associated with a lower mean age at time of vaccination (P=0.0495). The age at administration of the last CPV vaccination a puppy received prior to presenting with disease was a significant (P=0.0334) risk factor for vaccination failure, irrespective of whether the vaccine was marketed for a 10-week or 12-week or greater vaccination finish protocol. There was also a strong negative correlation between age at last vaccination prior to disease and vaccination failure (P<0.0001): the later a puppy received this last vaccination, the lower the risk of vaccination failure. This supports the hypothesis that the use of final vaccination in puppies at less than 16 weeks of age predisposes to vaccination failure and warrants a final age for vaccination recommendation to be at least 16 weeks for all canine parvovirus vaccines, especially in outbreak situations. The large number of cases identified in this study confirms that CPV vaccination failure is occurring in Australia. Veterinarians should consider CPV as a differential diagnosis in cases with appropriate clinical presentation, regardless of the reported vaccination status of the dog. Copyright © 2017

Which influenza vaccine formulation should be used in Kenya? A comparison of influenza isolates from Kenya to vaccine strains, 2007-2013.

PubMed

Waiboci, Lilian W; Mott, Joshua A; Kikwai, Gilbert; Arunga, Geoffrey; Xu, Xiyan; Mayieka, Lilian; Emukule, Gideon O; Muthoka, Phillip; Njenga, M Kariuki; Fields, Barry S; Katz, Mark A

2016-05-17

Every year the World Health Organization (WHO) recommends which influenza virus strains should be included in a northern hemisphere (NH) and a southern hemisphere (SH) influenza vaccine. To determine the best vaccine formulation for Kenya, we compared influenza viruses collected in Kenya from April 2007 to May 2013 to WHO vaccine strains. We collected nasopharyngeal and oropharyngeal (NP/OP) specimens from patients with respiratory illness, tested them for influenza, isolated influenza viruses from a proportion of positive specimens, tested the isolates for antigenic relatedness to vaccine strains, and determined the percentage match between circulating viruses and SH or NH influenza vaccine composition and schedule. During the six years, 7.336 of the 60,072 (12.2%) NP/OP specimens we collected were positive for influenza: 30,167 specimens were collected during the SH seasons and 3717 (12.3%) were positive for influenza; 2903 (78.1%) influenza A, 902 (24.2%) influenza B, and 88 (2.4%) influenza A and B positive specimens. We collected 30,131 specimens during the NH seasons and 3978 (13.2%) were positive for influenza; 3181 (80.0%) influenza A, 851 (21.4%) influenza B, and 54 (1.4%) influenza A and B positive specimens. Overall, 362/460 (78.7%) isolates from the SH seasons and 316/338 (93.5%) isolates from the NH seasons were matched to the SH and the NH vaccine strains, respectively (p<0.001). Overall, 53.6% and 46.4% SH and NH vaccines, respectively, matched circulating strains in terms of vaccine strains and timing. In six years of surveillance in Kenya, influenza circulated at nearly equal levels during the SH and the NH influenza seasons. Circulating viruses were matched to vaccine strains. The vaccine match decreased when both vaccine strains and timing were taken into consideration. Either vaccine formulation could be suitable for use in Kenya but the optimal timing for influenza vaccination needs to be determined. Copyright © 2016 Elsevier Ltd. All rights

The Bulgarian vaccine Crimean-Congo haemorrhagic fever virus strain.

PubMed

Papa, Anna; Papadimitriou, Evangelia; Christova, Iva

2011-03-01

The Crimean-Congo haemorrhagic fever virus (CCHFV) is a 3-segmented RNA virus, which causes disease with a high fatality rate in humans. An inactivated suckling mouse brain-derived vaccine is used in Bulgaria for protection against CCHF. Strain V42/81 is currently used for the vaccine preparation. As the M-RNA segment plays a major role in the immune response, the full-length M segment sequence of the V42/81 strain was characterized. A great genetic diversity was observed among CCHFV strains. In order to gain an insight into the topology of the strain in the CCHFV phylogenetic trees, the full-length S and partial L segments were additionally sequenced and analyzed.

Identification and development of a promising novel mumps vaccine candidate strain.

PubMed

Liang, Yan; Ma, Shaohui; Liu, Longding; Zhao, Hongling; Wang, Lichun; Jiang, Li; Xie, Zhongping; Dong, Chenghong; Li, Qihan

2010-12-01

Mumps epidemics are usually caused by airborne transmission of mumps virus (MuV) and have high morbidity in non-immunized children. Epidemiological studies in many regions of China show that the genotype F viral strain is the most prevalent. However, the genotype A strain is currently used to prepare vaccines. Regional epidemiological MuV data suggest a significant application for the development of live attenuated mumps vaccines targeting specific genotypes. This article reports the isolation and culture of a genotype F MuV candidate strain that could be used to prepare a live attenuated mumps vaccine. This strain is shown to have good immunological efficacy and stability in neurovirulence evaluations. This work should facilitate the implementation of mumps vaccination in mainland China by targeting the most prevalent MuV genotype, genotype F. Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.

Inability to induce consistent T-cell responses recognizing conserved regions within HIIV-1 antigens: a potential mechanism for lack of vaccine efficacy in the step study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korber, Bette; Szinger, James

2009-01-01

T cell based vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a high probability of matching the epitope induced by vaccination with the infecting viral strain. We compared the frequency and specificity of the CTL epitopes elicited by the replication defective AdS gag/pol/nef vaccine used in the STEP trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. On average vaccination elicited only one epitope per gene. Importantly, the highly conservedmore » epitopes in gag, pol, and nef (> 80% of strains in the current collection of the Los Alamos database [www.hiv.lanl.gov]) were rarely elicited by vaccination. Moreover there was a statistically significant skewing of the T cell response to relative variable epitopes of each gene; only 20% of persons possessed > 3 T cell responses to epitopes likely to be found in circulating strains in the CladeB populations in which the Step trial was conducted. This inability to elicit T cell responses likely to be found in circulating viral strains is a likely factor in the lack of efficacy of the vaccine utilized in the STEP trial. Modeling of the epitope specific responses elicited by vaccination, we project that a median of 8-10 CD8+ T cell epitopes are required to provide >80% likelihood of eliciting at least 3 CD8+ T cell epitopes that would be found on a circulating population of viruses. Development of vaccine regimens which elicit either a greater breadth of responses or elicit responses to conserved regions of the HIV-1 genome are needed to fully evaluate the concept of whether induction of T cell immunity can alter HIV-1 in vivo.« less

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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

Correlation of mutations and recombination with growth kinetics of poliovirus vaccine strains.

PubMed

Pliaka, V; Kyriakopoulou, Z; Tsakogiannis, D; Ruether, I G A; Gartzonika, C; Levidiotou-Stefanou, S; Krikelis, A; Markoulatos, P

2010-12-01

Attenuated strains of Sabin poliovirus vaccine replicate in the human gut and, in rare cases, may cause vaccine-associated paralytic poliomyelitis (VAPP). The genetic instability of Sabin strains constitutes one of the main causes of VAPP, a disease that is most frequently associated with type 3 and type 2 Sabin strains, and more rarely with type 1 Sabin strains. In the present study, the growth phenotype of eight oral poliovirus vaccine (OPV) isolates (two non-recombinants and six recombinants), as well as of Sabin vaccine strains, was evaluated using two different assays, the reproductive capacity at different temperatures (Rct) test and the one-step growth curve test in Hep-2 cells at two different temperatures (37°C and 40°C). The growth phenotype of isolates was correlated with genomic modifications in order to identify the determinants and mechanisms of reversion towards neurovirulence. All of the recombinant OPV isolates showed a thermoresistant phenotype in the Rct test. Moreover, both recombinant Sabin-3 isolates showed significantly higher viral yield than Sabin 3 vaccine strain at 37°C and 40°C in the one-step growth curve test. All of the OPV isolates displayed mutations at specific sites of the viral genome, which are associated with the attenuated and temperature-sensitive phenotype of Sabin strains. The results showed that both mutations and recombination events could affect the phenotype traits of Sabin derivatives and may lead to the reversion of vaccinal strains to neurovirulent ones. The use of phenotypic markers along with the genomic analysis may shed additional light on the molecular determinants of the reversed neurovirulent phenotype of Sabin derivatives.

Correlation of genetic variability with safety of mumps vaccine Urabe AM9 strain.

PubMed

Amexis, G; Fineschi, N; Chumakov, K

2001-08-15

The Urabe AM9 strain of mumps vaccine live is known for its genetic instability and some vaccines derived from this strain were withdrawn from the market due to an excessive number of vaccine-associated parotitis and meningitis cases. To identify the molecular basis of this instability, we determined complete nucleotide sequences of several stocks of the Urabe strain used for vaccine production by different manufacturers and of two clinical isolates from cases of vaccine-associated meningitis. In contrast to previously published studies relating the Lys335 --> Glu mutation in the viral HN gene with neurovirulence of mumps virus, we could not confirm any association of this mutation with the safety of mumps vaccine. Each of the three vaccine stocks studied had its own characteristic profile of mutations that was identified by cDNA sequencing and quantitated by mutant analysis by PCR and restriction enzyme cleavage. Determination of the mutational profile of mumps vaccine lots could allow vaccine manufacturers to characterize seed viruses and monitor the consistency of vaccine production to prevent emergence of virulent revertants.

The risk of aseptic meningitis associated with the Leningrad-Zagreb mumps vaccine strain following mass vaccination with measles-mumps-rubella vaccine, Rio Grande do Sul, Brazil, 1997.

PubMed

da Silveira, Claudio Marcos; Kmetzsch, Claudete Iris; Mohrdieck, Renate; Sperb, Alethea Fagundes; Prevots, D Rebecca

2002-10-01

Few data are available on the risk of aseptic meningitis following vaccination with the Leningrad-Zagreb (L-Z) strain of mumps vaccine. In 1997 the mumps vaccine was introduced into the state of Rio Grande do Sul in Brazil through mass vaccination with mumps-measles-rubella (MMR), targeting children aged 1-11 years. Five municipalities used exclusively MMR vaccine containing the L-Z strain of mumps. An outbreak of aseptic meningitis was observed shortly after the mass campaign. To estimate the risk of aseptic meningitis associated with this strain, we analysed vaccination and meningitis case surveillance data from the selected municipalities. A case of vaccine-associated aseptic meningitis was defined as one with a pleocytosis of 10-1,500 leukocytes/ml and occurring within 15-35 days after vaccine receipt. We estimated a risk of 2.9 cases per 10,000 doses of L-Z administered, equivalent to 1 case per 3,390 doses administered. The overall risk of aseptic meningitis following the campaign was increased 12.2-fold (95% CI: 6.0-24.7) compared with the same period in 1995-1996. Following the mass campaign, the incidence of mumps declined 93% during 1998-2000. Vaccination with the L-Z strain of mumps vaccine as part of a mass campaign was associated with a significantly increased risk of aseptic meningitis. Decisions about type of mumps vaccine and mumps vaccination strategies must consider vaccine safety issues in addition to other criteria.

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

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.

Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

PubMed Central

Abdallah, Abdallah M.; Hill-Cawthorne, Grant A.; Otto, Thomas D.; Coll, Francesc; Guerra-Assunção, José Afonso; Gao, Ge; Naeem, Raeece; Ansari, Hifzur; Malas, Tareq B.; Adroub, Sabir A.; Verboom, Theo; Ummels, Roy; Zhang, Huoming; Panigrahi, Aswini Kumar; McNerney, Ruth; Brosch, Roland; Clark, Taane G.; Behr, Marcel A.; Bitter, Wilbert; Pain, Arnab

2015-01-01

Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains. PMID:26487098

Protective immunity spectrum induced by immunization with a vaccine from the TBEV strain Sofjin.

PubMed

Chernokhaeva, L L; Rogova, Yu V; Vorovitch, M F; Romanova, L Iu; Kozlovskaya, L I; Maikova, G B; Kholodilov, I S; Karganova, G G

2016-04-29

Tick-borne encephalitis (TBE) circulates widely in the territory of Eurasia with up to 10,000 cases registered annually. The TBE virus (TBEV) includes three main subtypes: European, Siberian and Far-Eastern, and two new Asiatic variants, phylogenetically distant from the others. The inactivated antigen of European or Far-Eastern strains is used in commercial TBE vaccines. A set of 14 TBEV strains, isolated in 1937-2008, with different passage histories, representing all subtypes and variants, was used in this work. The chosen set covers almost all the TBE area. Sera of mice, immunized with the TBE vaccine Moscow, prepared from the TBEV strain Sofjin, were studied in a plaque neutralization test against the set of TBEV strains. The vaccine induced antibodies at a protective titer against all TBEV strains and Omsk hemorrhagic fever virus (OHFV) with Е protein amino acid distances of 0.008-0.069, but not against Powassan virus. We showed that after a course of two immunizations, factors such as the period between vaccinations (1-4 weeks), the challenging virus dose (30-1000 LD50) and terms of challenge (1-4 weeks after the last immunization) did not significantly affect the assessment of protective efficacy of the vaccine in vivo. The protective effect of the TBE vaccine Moscow against the set of TBEV strains and the OHFV was demonstrated in in vivo experiments. TBE vaccine Moscow did not protect mice against 10 LD50 of the Powassan virus. We showed that this range of Е protein amino acid distances between the vaccine strain and challenging virus do not have a decisive impact on the TBE vaccine protective effect in vitro and in vivo. Moreover, the TBE vaccine Moscow induces an immune response protective against a wide range of TBEV variants. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Study on the neutralization capacity of different types of human measles virus vaccine and the epidemic strains].

PubMed

Feng, Yan; Lu, Yi-yu; Yan, Ju-ying; Jiang, Xiao-hui; Shi, Wen; Xu, Chang-ping; Li, Zhen

2007-11-01

To explore the neutralization capacities of different types of human serum to measles virus epidemic strains and vaccine strain. Neutralization antibody (NT) to Shanghai 191 and measles virus isolates in 2005 were tested using acute and convalescent serum samples from diagnosed measles patients, children serum samples collected before and after vaccination and serum samples of migrant residents, from 3 different regions. Additionally, animal immune serum referring to vaccine strain and 3 epidemic strains were prepared and used to undergo crossing neutralization test with corresponding strains mentioned-above. Antigenic ratios were calculated. GMT value of NT of after-immune serum to vaccine strains was 50.82,1.86 times higher than that to MVi/ZJ/05/7 (GMT was 27.35), whereas GMT value of convalescent serum to MVi/ZJ/05/7 (GMT was 386.95) was obviously higher than that to vaccine strain (GMT was 1:151.83),and GMT value of migrant residents' serum in 3 regions to MVi/ZJ/05/7 were 2.22-4.17 times lower than that to vaccine strain. Meanwhile,the antigenic ratios between MVi/ZJ/ 99/1, MVi/ZJ/04/1, MVi/ZJ/05/7 and vaccine strain were found to be 4.28,5.24 and 5.66 respectively. Additionally,low NT titers to vaccine strain were found in patients' acute sera and GMT value was over 1:4. There were obvious differences on neutralization antibody of different types of serum to measles vaccine strain and epidemic strains which indicating the antigenic diversity of epidemic strains had influenced the protective effectiveness of vaccine antibody to epidemic strains. It was of significance to carry on research projects on the antigenic diversity and effectiveness of measles vaccine.

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

PubMed Central

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

2016-01-01

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. PMID:27511964

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.

T-cell-mediated cross-strain protective immunity elicited by prime-boost vaccination with a live attenuated influenza vaccine.

PubMed

Li, Junwei; Arévalo, Maria T; Chen, Yanping; Chen, Shan; Zeng, Mingtao

2014-10-01

Antigenic drift and shift of influenza viruses require frequent reformulation of influenza vaccines. In addition, seasonal influenza vaccines are often mismatched to the epidemic influenza strains. This stresses the need for a universal influenza vaccine. BALB/c mice were vaccinated with the trivalent live attenuated (LAIV; FluMist) or inactivated (TIV; FluZone) influenza vaccines and challenged with PR8 (H1N1), FM/47 (H1N1), or HK/68 (H3N2) influenza virus. Cytokines and antibody responses were tested by ELISA. Furthermore, different LAIV dosages were applied in BALB/c mice. LAIV vaccinated mice were also depleted of T-cells and challenged with PR8 virus. LAIV induced significant protection against challenge with the non-vaccine strain PR8 influenza virus. Furthermore, protective immunity against PR8 was dose-dependent. Of note, interleukin 2 and interferon gamma cytokine secretion in the lung alveolar fluid were significantly elevated in mice vaccinated with LAIV. Moreover, T-cell depletion of LAIV vaccinated mice compromised protection, indicating that T-cell-mediated immunity is required. In contrast, passive transfer of sera from mice vaccinated with LAIV into naïve mice failed to protect against PR8 challenge. Neutralization assays in vitro confirmed that LAIV did not induce cross-strain neutralizing antibodies against PR8 virus. Finally, we showed that three doses of LAIV also provided protection against challenge with two additional heterologous viruses, FM/47 and HK/68. These results support the potential use of the LAIV as a universal influenza vaccine under a prime-boost vaccination regimen. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Experimental infection of horses with an attenuated Venezuelan equine encephalomyelitis vaccine (strain TC-83).

PubMed

Walton, T E; Alvarez, O; Buckwalter, R M; Johnson, K M

1972-05-01

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 10(3.5) 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.

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

Egg quality in laying hens exposed to Mycoplasma gallisepticum F-strain attenuated vaccine.

PubMed

Machado, L D S; Santos, F F D; Togashi, C K; Abreu, D L D C; Pimentel, J C; Sesti, L; Pereira, V L D A; Nascimento, E R D

2017-04-01

Mycoplasma gallisepticum causes coughing, ocular and nasal discharge, reduction in feed intake, lower and uneven growth, decline in egg production and quality, and increase in mortality. Among the attenuated vaccination strains, MGF can reduce clinical signs and lesions in layer hens, stimulate immune responses of cellular and humoral basis, act as an instrument of competitive exclusion in relation to field strains, and reduce the use of antimicrobials. This study aimed to investigate the effects of attenuated MG F-strain vaccination on egg quality in 3 groups of 30 hens each, being one control and 2 vaccinated. Vaccination was applied by ocular route at 8 and 12 wk of age. Comparisons were made among unvaccinated hens; vaccinated at 8 wk of age; and vaccinated at 8 and 12 wk of age. There were no statistical differences in eggshell thickness and weight among groups. Eggs from twice vaccinated birds yielded a Haugh unit significantly lower than the other groups without affecting egg classification. There was no significant difference in ELISA results between the vaccinated groups. © 2016 Poultry Science Association Inc.

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

PubMed

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

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(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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Danher; Hevey, Michael; Juompan, Laure Y.

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 guineamore » 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.« less

Association of deficiency in antibody response to vaccine and heterogeneity of Ehrlichia risticii strains with Potomac horse fever vaccine failure in horses.

PubMed

Dutta, S K; Vemulapalli, R; Biswas, B

1998-02-01

Ehrlichia risticii is the causative agent of Potomac horse fever (PHF), which continues to be an important disease of horses. Commercial inactivated whole-cell vaccines are regularly used for immunization of horses against the disease. However, PHF is occurring in large numbers of horses in spite of vaccination. In a limited study, 43 confirmed cases of PHF occurred between the 1994 and 1996 seasons; of these, 38 (89%) were in horses that had been vaccinated for the respective season, thereby clearly indicating vaccine failure. A field study of horses vaccinated with two PHF vaccines indicated a poor antibody response, as determined by immunofluorescence assay (IFA) titers. In a majority of horses, the final antibody titer ranged between 40 and 1,280, in spite of repeated vaccinations. None of the vaccinated horses developed in vitro neutralizing antibody in their sera. Similarly, one horse experimentally vaccinated three times with one of the vaccines showed a poor antibody response, with final IFA titers between 80 and 160. The horse did not develop in vitro neutralizing antibody or antibody against the 50/85-kDa strain-specific antigen (SSA), which is the protective antigen of the original strain, 25-D, and the variant strain of our laboratory, strain 90-12. Upon challenge infection with the 90-12 strain, the horse showed clinical signs of the disease. The horse developed neutralizing antibody and antibody to the 50/85-kDa SSA following the infection. Studies of the new E. risticii isolates from the field cases indicated that they were heterogeneous among themselves and showed differences from the 25-D and 90-12 strains as determined by IFA reactivity pattern, DNA amplification finger printing profile, and in vitro neutralization activity. Most importantly, the molecular sizes of the SSA of these isolates varied, ranging from 48 to 85 kDa. These studies suggest that the deficiency in the antibody response to the PHF vaccines and the heterogeneity of E. risticii

Association of Deficiency in Antibody Response to Vaccine and Heterogeneity of Ehrlichia risticii Strains with Potomac Horse Fever Vaccine Failure in Horses

PubMed Central

Dutta, Sukanta K.; Vemulapalli, Ramesh; Biswas, Biswajit

1998-01-01

Ehrlichia risticii is the causative agent of Potomac horse fever (PHF), which continues to be an important disease of horses. Commercial inactivated whole-cell vaccines are regularly used for immunization of horses against the disease. However, PHF is occurring in large numbers of horses in spite of vaccination. In a limited study, 43 confirmed cases of PHF occurred between the 1994 and 1996 seasons; of these, 38 (89%) were in horses that had been vaccinated for the respective season, thereby clearly indicating vaccine failure. A field study of horses vaccinated with two PHF vaccines indicated a poor antibody response, as determined by immunofluorescence assay (IFA) titers. In a majority of horses, the final antibody titer ranged between 40 and 1,280, in spite of repeated vaccinations. None of the vaccinated horses developed in vitro neutralizing antibody in their sera. Similarly, one horse experimentally vaccinated three times with one of the vaccines showed a poor antibody response, with final IFA titers between 80 and 160. The horse did not develop in vitro neutralizing antibody or antibody against the 50/85-kDa strain-specific antigen (SSA), which is the protective antigen of the original strain, 25-D, and the variant strain of our laboratory, strain 90-12. Upon challenge infection with the 90-12 strain, the horse showed clinical signs of the disease. The horse developed neutralizing antibody and antibody to the 50/85-kDa SSA following the infection. Studies of the new E. risticii isolates from the field cases indicated that they were heterogeneous among themselves and showed differences from the 25-D and 90-12 strains as determined by IFA reactivity pattern, DNA amplification finger printing profile, and in vitro neutralization activity. Most importantly, the molecular sizes of the SSA of these isolates varied, ranging from 48 to 85 kDa. These studies suggest that the deficiency in the antibody response to the PHF vaccines and the heterogeneity of E. risticii

Molecular characterisation and nucleotide sequence analysis of canine parvovirus strains in vaccines in India.

PubMed

Nandi, Sukdeb; Anbazhagan, Rajendra; Kumar, Manoj

2010-01-01

Canine parvovirus 2 (CPV-2) is one of the most important viruses that causes haemorrhagic gastroenteritis and myocarditis of dogs worldwide. The picture has been complicated further due to the emergence of new mutants of CPV, namely: CPV-2a, CPV-2b and CPV-2c. In this study, the molecular characterisation of strains present in the CPV vaccines available on the Indian market was performed using polymerase chain reaction and DNA sequencing. The VP1/VP2 genes of two vaccine strains and a field strain (Bhopal) were sequenced and the nucleotide and the deduced amino acid sequences were compared. The results indicated that the isolate belonged to CPV type 2b and the strains in the vaccines belonged to type CPV-2. From the study, it is inferred that the CPV strain used in commercially available vaccine preparation differed from the strains present in CPV infection in dogs in India.

Antibodies Against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals From Infection With Contemporary Circulating Influenza A(H1N1) Virus Strains.

PubMed

Petrie, Joshua G; Parkhouse, Kaela; Ohmit, Suzanne E; Malosh, Ryan E; Monto, Arnold S; Hensley, Scott E

2016-12-15

During the 2013-2014 influenza season, nearly all circulating 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) strains possessed an antigenically important mutation in hemagglutinin (K166Q). Here, we performed hemagglutination-inhibition (HAI) assays, using sera collected from 382 individuals prior to the 2013-2014 season, and we determined whether HAI titers were associated with protection from A(H1N1)pdm09 infection. Protection was associated with HAI titers against an A(H1N1)pdm09 strain possessing the K166Q mutation but not with HAI titers against the current A(H1N1)pdm09 vaccine strain, which lacks this mutation. These data indicate that contemporary A(H1N1)pdm09 strains are antigenically distinct from the current A(H1N1)pdm09 vaccine strain. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain.

PubMed

Raymond, Donald D; Stewart, Shaun M; Lee, Jiwon; Ferdman, Jack; Bajic, Goran; Do, Khoi T; Ernandes, Michael J; Suphaphiphat, Pirada; Settembre, Ethan C; Dormitzer, Philip R; Del Giudice, Giuseppe; Finco, Oretta; Kang, Tae Hyun; Ippolito, Gregory C; Georgiou, George; Kepler, Thomas B; Haynes, Barton F; Moody, M Anthony; Liao, Hua-Xin; Schmidt, Aaron G; Harrison, Stephen C

2016-12-01

For broad protection against infection by viruses such as influenza or HIV, vaccines should elicit antibodies that bind conserved viral epitopes, such as the receptor-binding site (RBS). RBS-directed antibodies have been described for both HIV and influenza virus, and the design of immunogens to elicit them is a goal of vaccine research in both fields. Residues in the RBS of influenza virus hemagglutinin (HA) determine a preference for the avian or human receptor, α-2,3-linked sialic acid and α-2,6-linked sialic acid, respectively. Transmission of an avian-origin virus between humans generally requires one or more mutations in the sequences encoding the influenza virus RBS to change the preferred receptor from avian to human, but passage of a human-derived vaccine candidate in chicken eggs can select for reversion to avian receptor preference. For example, the X-181 strain of the 2009 new pandemic H1N1 influenza virus, derived from the A/California/07/2009 isolate and used in essentially all vaccines since 2009, has arginine at position 226, a residue known to confer preference for an α-2,3 linkage in H1 subtype viruses; the wild-type A/California/07/2009 isolate, like most circulating human H1N1 viruses, has glutamine at position 226. We describe, from three different individuals, RBS-directed antibodies that recognize the avian-adapted H1 strain in current influenza vaccines but not the circulating new pandemic 2009 virus; Arg226 in the vaccine-strain RBS accounts for the restriction. The polyclonal sera of the three donors also reflect this preference. Therefore, when vaccines produced from strains that are never passaged in avian cells become widely available, they may prove more capable of eliciting RBS-directed, broadly neutralizing antibodies than those produced from egg-adapted viruses, extending the established benefits of current seasonal influenza immunizations.

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

PubMed Central

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. PMID:24396177

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.

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.

Herpes Zoster Caused by Vaccine-Strain Varicella Zoster Virus in an Immunocompetent Recipient of Zoster Vaccine

PubMed Central

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

2014-01-01

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. PMID:24470276

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. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Reverse spillover of avian viral vaccine strains from domesticated poultry to wild birds.

PubMed

Rohaim, M A; El Naggar, R F; Helal, A M; Hussein, H A; Munir, Muhammad

2017-06-16

Transmission of viruses from the commercial poultry to wild birds is an emerging paradigm of livestock-wildlife interface. Here, we report the identification and isolation of vaccine strains of avian paramyxovirus serotype 1 (APMV1) and avian coronaviruses (ACoV) from different wild bird species across eight Egyptian governorates between January 2014 and December 2015. Surveillance of avian respiratory viruses in free-ranging wild birds (n=297) identified three species that harboured or excreted APMV1 and ACoVs. Genetic characterization and phylogenetic analysis of recovered viruses revealed a close association with the most widely utilized vaccine strains in the country. These results highlight the potential spillover of vaccine-viruses probably due to extensive use of live-attenuated vaccines in the commercial poultry, and close interaction between domesticated and wild bird populations. Further exploring the full spectrum of vaccine-derived viral vaccine strains in wild birds might help to assess the emergence of future wild-birds origin viruses. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Persistence and spreading of field and vaccine strains of infectious laryngotracheitis virus (ILTV) in vaccinated and unvaccinated geographic regions, in Brazil.

PubMed

Chacón, Jorge Luis; Núñez, Luis Fabian Naranjo; Vejarano, Maria Pilar; Parra, Silvana Hipatia Santander; Astolfi-Ferreira, Claudete Serrano; Ferreira, Antonio José Piantino

2015-08-01

Infectious laryngotracheitis (ILT) is a highly infectious respiratory disease that causes morbidity and mortality in commercial chickens. Despite the use of attenuated vaccines, ILT outbreaks have been described in broiler and long-lived birds. Molecular approaches, including polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing, are used to characterize ILT viruses (ILTVs) detected in vaccinated and unvaccinated geographical regions. As part of an ILT control program implemented in a region of commercial layer production, samples of conjunctiva, trachea, and trigeminal ganglia were collected from chickens in a vaccinated and quarantined region over a period of 8 years after initiation of vaccination. To determine the origin of new ILT outbreaks in unvaccinated regions, samples collected from ill chickens were also analyzed. Chicken embryo origin (CEO) vaccine viruses and the Bastos field strain were detected circulating in healthy chickens in the vaccinated region. CEO strains and field viruses molecularly related to the Bastos strain were also detected outside of the quarantined region in chickens showing clinical signs of ILT. This study reveals the persistence and circulation of a wild field strain, despite the intensive use of tissue culture origin (TCO) and CEO vaccines in a quarantined region. Spreading of CEO viruses to unvaccinated regions and the capacity of this virus to establish latent infections and cause severe outbreaks were also observed.

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.

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Strain diversity plays no major role in the varying efficacy of rotavirus vaccines: an overview.

PubMed

Velasquez, Daniel E; Parashar, Umesh D; Jiang, Baoming

2014-12-01

While a monovalent Rotarix® [RV1] and a pentavalent RotaTeq® [RV5] have been extensively tested and found generally safe and equally efficacious in clinical trials, the question still lingers about the evolving diversity of circulating rotavirus strains over time and their relationship with protective immunity induced by rotavirus vaccines. We reviewed data from clinical trials and observational studies that assessed the efficacy or field effectiveness of rotavirus vaccines against different rotavirus strains worldwide. RV1 provided broad clinical efficacy and field effectiveness against severe diarrhea due to all major circulating strains, including the homotypic G1P[8] and the fully heterotypic G2P[4] strains. Similarly, RV5 provided broad efficacy and effectiveness against RV5 and non-RV5 strains throughout different locations. Rotavirus vaccination provides broad heterotypic protection; however continuing surveillance is needed to track the change of circulating strains and monitor the effectiveness and safety of vaccines. Published by Elsevier B.V.

Classical Swine Fever Outbreak after Modified Live LOM Strain Vaccination in Naive Pigs, South Korea

PubMed Central

Je, Sang H.; Kwon, Taeyong; Yoo, Sung J.; Lee, Dong-Uk; Lee, SeungYoon; Richt, Juergen A.

2018-01-01

We report classical swine fever outbreaks occurring in naive pig herds on Jeju Island, South Korea, after the introduction of the LOM vaccine strain. Two isolates from sick pigs had >99% identity with the vaccine stain. LOM strain does not appear safe; its use in the vaccine should be reconsidered. PMID:29553332

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

Inactivation of SAM-Methyltransferase is the Mechanism of Attenuation of a Historic Louse Borne Typhus Vaccine Strain

PubMed Central

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. PMID:25412248

A clinical trial of WRL 105 strain live attenuated influenza vaccine comparing four methods of intranasal vaccination.

PubMed Central

Freestone, D. S.; Bowker, C. H.; Letley, E.; Ferris, R. D.; White, W. G.; Barnes, G. M.

1976-01-01

A single intranasal dose of 10(7-0) EID50 recombinant WRL 105 strain live attenuated influenza vaccine was administered intranasally to 193 volunteers either as nose drops or by one of three spray devices which produced sprays of differing physical characteristics. In volunteers with homologous haemagglutinating inhibiting antibody titres of less than or equal to 20 before vaccination, seroconversion rates varied widely from 80% following the administration of drops to 71%, 57% and 28% with the three spray devices. In the week following vaccination 16 (22%) of 74 volunteers who were found to show a fourfold or greater antibody response to took analgesics to control symptoms in comparison with 4 (7%) of 58 volunteers who exhibited no serological response to vaccination (P less than 0-05). However, neither the occurrence of upper respiratory nor systemic symptoms were significantly different in these two groups and the degree of attenuation of the recombinant WRL 105 strain appears to be acceptable for future use. PMID:1064672

Low Dose Vaccination with Attenuated Francisella tularensis Strain SchuS4 Mutants Protects against Tularemia Independent of the Route of Vaccination

PubMed Central

Rockx-Brouwer, Dedeke; Chong, Audrey; Wehrly, Tara D.; Child, Robert; Crane, Deborah D.

2012-01-01

Tularemia, caused by the Gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protect against tularemia. However, lower vaccinating inoculums did not offer similar immunity. One concern of using live vaccines is that the host may develop mild tularemia in response to infection and use of high inoculums may contribute to this issue. Thus, generation of a live vaccine that can efficiently protect against tularemia when delivered in low numbers, e.g. <100 organisms, may address this concern. Herein we describe the ability of three defined, attenuated mutants of F. tularensis SchuS4, deleted for FTT0369c, FTT1676, or FTT0369c and FTT1676, respectively, to engender protective immunity against tularemia when delivered at concentrations of approximately 50 or fewer bacteria. Attenuated strains for use as vaccines were selected by their inability to efficiently replicate in macrophages in vitro and impaired replication and dissemination in vivo. Although all strains were defective for replication in vitro within macrophages, protective efficacy of each attenuated mutant was correlated with their ability to modestly replicate and disseminate in the host. Finally, we demonstrate the parenteral vaccination with these strains offered superior protection against pneumonic tularemia than intranasal vaccination. Together our data provides proof of principle that low dose attenuated vaccines may be a viable goal in development of novel vaccines directed against tularemia. PMID:22662210

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

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.

[Virus strain specific serum neutralizing antibodies in children and adolescents immunized with a Russian mumps vaccine].

PubMed

Otrashevskaia, E V; Krasil'nikov, I V; Ignat'ev, G M

2010-01-01

Postvaccination immunity was studied in the children and teenagers without a history of clinical mumps infection, who had been immunized with the Leningrad-3 mumps vaccine. The level of specific lgG in ELISA and that and spectrum of their neutralizing activity against a vaccine strain and three heterologous mumps virus (MV) strains (genotypes A, C, and H) were measured. The investigation included 151 sera from the vaccinees aged 3 to 17 years, possessing the detectable specific IgG titers in ELISA and the detectable neutralizing titers against the vaccine strain. 97.4% of the vaccinees had neutralizing activity against 1-3 heterologous MV strains. A preponderance of neutralizing titers against heterologous MV strains by 1-log2 in some sera (6.5-32.5 depending on age) was most likely to suggest that the vaccinees' had been in contact with these virus strains in the past. In our investigation, a combination of positive IgG titers and neutralizing titers against the vaccine strain 2-log2 or higher provided the protection of the vaccinated children and teenagers against the symptomatic infection. There was a pronounced buster effect of the second immunization and a drop in the neutralizing activity of the sera from the vaccinated children and adolescents over time after the first and second immunization.

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.

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. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

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

[Isolation and identification of Lyssavirus strains from an area of Slovakia where oral antirabies vaccine was administered].

PubMed

Ondrejka, R; Durove, A; Svrcek, S; Benísek, Z; Süliová, J

1997-02-01

The study was aimed at isolation and subsequent identification of strains of rabies virus by means of monoclonal antibodies from foxes killed in the vaccination zone within the complex preliminary monitoring of oral antirabies vaccination. The results obtained indicate that the vaccines for oral antirabies vaccination used in Slovakia did not contain any vaccination strain pathogenic to the extremely sensitive target species-the fox (Vulpes vulpes).

Genetic and antigenic characterization of serotype O FMD viruses from East Africa for the selection of suitable vaccine strain.

PubMed

Lloyd-Jones, Katie; Mahapatra, Mana; Upadhyaya, Sasmita; Paton, David J; Babu, Aravindh; Hutchings, Geoff; Parida, Satya

2017-12-14

Foot-and-mouth disease (FMD) is endemic in Eastern Africa with circulation of multiple serotypes of the virus in the region. Most of the outbreaks are caused by serotype O followed by serotype A. The lack of concerted FMD control programmes in Africa has provided little incentive for vaccine producers to select vaccines that are tailored to circulating regional isolates creating further negative feedback to deter the introduction of vaccine-based control schemes. In this study a total of 80 serotype O FMD viruses (FMDV) isolated from 1993 to 2012 from East and North Africa were characterized by virus neutralisation tests using bovine antisera to three existing (O/KEN/77/78, O/Manisa and O/PanAsia-2) and three putative (O/EA/2002, O/EA/2009 and O/EA/2010) vaccine strains and by capsid sequencing. Genetically, these viruses were grouped as either of East African origin with subdivision into four topotypes (EA-1, 2, 3 and 4) or of Middle-East South Asian (ME-SA) topotype. The ME-SA topotype viruses were mainly detected in Egypt and Libya reflecting the trade links with the Middle East countries. There was good serological cross-reactivity between the vaccine strains and most of the field isolates analysed, indicating that vaccine selection should not be a major constraint for control of serotype O FMD by vaccination, and that both local and internationally available commercial vaccines could be used. The O/KEN/77/78 vaccine, commonly used in the region, exhibited comparatively lower percent in vitro match against the predominant topotypes (EA-2 and EA-3) circulating in the region whereas O/PanAsia-2 and O/Manisa vaccines revealed broader protection against East African serotype O viruses, even though they genetically belong to the ME-SA topotype. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Evaluation of Brucella abortus strain RB51 and strain 19 in pronghorn antelope

USGS Publications Warehouse

Elzer, P.H.; Smith, J.; Roffe, T.; Kreeger, T.; Edwards, J.; Davis, D.

2002-01-01

Free-roaming elk and bison in the Greater Yellowstone Area remain the only wildlife reservoirs for Brucella abortus in the United States, and the large number of animals and a lack of holding facilities make it unreasonable to individually vaccinate each animal. Therefore, oral delivery is being proposed as a possible option to vaccinate these wild ungulates. One of the main problems associated with oral vaccination is the potential exposure of nontarget species to the vaccines. The purpose of this study was to determine the effects of two Brucella vaccines, strain 19 (S19) and the rough strain RB51 (SRB51), in pregnant pronghorn antelope. We conclude that S19 and SRB51 rarely colonize maternal and fetal tissues of pregnant pronghorn and were not associated with fetal death. Oral delivery of either vaccine at this dose appears to be nonhazardous to pregnant pronghorn.

Generation of a Listeria vaccine strain by enhanced Caspase-1 activation

PubMed Central

Warren, Sarah E.; Duong, Hien; Mao, Dat Phat; Armstrong, Abraham; Rajan, Jayant; Miao, Edward A.; Aderem, Alan

2012-01-01

The immunostimulatory properties conferred by vaccine adjuvants require Caspase-1 for processing of IL-1β and IL-18. Caspase-1 is activated in response to a breach of the cytosolic compartment by microbes and the process is initiated by intracellular pattern recognition receptors within inflammasomes. Listeria monocytogenes is detected in the cytosol by the NLRC4, NLRP3 and AIM2 inflammasomes. NLRC4 is activated by flagellin, and L. monocytogenes evades this detector by repressing flagellin expression. We generated an L. monocytogenes strain that was forced to express flagellin in the host cell cytosol. This strain hyperactivated Caspase-1 and was preferentially cleared via NLRC4 detection in an IL-1β/IL-18 independent manner. We also created a strain of L. monocytogenes with forced expression of another NLRC4 agonist, PrgJ from the Type III secretion system of S. typhimurium. Forced expression of flagellin or PrgJ resulted in attenuation, yet both strains conferred protective immunity in mice against lethal challenge with L. monocytogenes. This work is the first demonstration of specific targeting of the Caspase-1 activation pathway to generate a safe and potent L. monocytogenes based vaccine. Moreover, the attenuated strains with embedded flagellin or PrgJ adjuvants, represent attractive vectors for vaccines aimed at eliciting T cell responses. PMID:21538346

Development and introduction of inactivated poliovirus vaccines derived from Sabin strains in Japan.

PubMed

Shimizu, Hiroyuki

2016-04-07

During the endgame of global polio eradication, the universal introduction of inactivated poliovirus vaccines is urgently required to reduce the risk of vaccine-associated paralytic poliomyelitis and polio outbreaks due to wild and vaccine-derived polioviruses. In particular, the development of inactivated poliovirus vaccines (IPVs) derived from the attenuated Sabin strains is considered to be a highly favorable option for the production of novel IPV that reduce the risk of facility-acquired transmission of poliovirus to the communities. In Japan, Sabin-derived IPVs (sIPVs) have been developed and introduced for routine immunization in November 2012. They are the first licensed sIPVs in the world. Consequently, trivalent oral poliovirus vaccine was used for polio control in Japan for more than half a century but has now been removed from the list of vaccines licensed for routine immunization. This paper reviews the development, introduction, characterization, and global status of IPV derived from attenuated Sabin strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

Autodisplay: Development of an Efficacious System for Surface Display of Antigenic Determinants in Salmonella Vaccine Strains

PubMed Central

Kramer, Uwe; Rizos, Konstantin; Apfel, Heiko; Autenrieth, Ingo B.; Lattemann, Claus T.

2003-01-01

To optimize antigen delivery by Salmonella vaccine strains, a system for surface display of antigenic determinants was established by using the autotransporter secretion pathway of gram-negative bacteria. A modular system for surface display allowed effective targeting of heterologous antigens or fragments thereof to the bacterial surface by the autotransporter domain of AIDA-I, the Escherichia coli adhesin involved in diffuse adherence. A major histocompatibility complex class II-restricted epitope, comprising amino acids 74 to 86 of the Yersinia enterocolitica heat shock protein Hsp60 (Hsp6074-86), was fused to the AIDA-I autotransporter domain, and the resulting fusion protein was expressed at high levels on the cell surface of E. coli and Salmonella enterica serovar Typhimurium. Colonization studies in mice vaccinated with Salmonella strains expressing AIDA-I fusion proteins demonstrated high genetic stability of the generated vaccine strain in vivo. Furthermore, a pronounced T-cell response against Yersinia Hsp6074-86 was induced in mice vaccinated with a Salmonella vaccine strain expressing the Hsp6074-86-AIDA-I fusion protein. This was shown by monitoring Yersinia Hsp60-stimulated IFN-γ secretion and proliferation of splenic T cells isolated from vaccinated mice. These results demonstrate that the surface display of antigenic determinants by the autotransporter pathway deserves special attention regarding the application in live attenuated Salmonella vaccine strains. PMID:12654812

Autodisplay: development of an efficacious system for surface display of antigenic determinants in Salmonella vaccine strains.

PubMed

Kramer, Uwe; Rizos, Konstantin; Apfel, Heiko; Autenrieth, Ingo B; Lattemann, Claus T

2003-04-01

To optimize antigen delivery by Salmonella vaccine strains, a system for surface display of antigenic determinants was established by using the autotransporter secretion pathway of gram-negative bacteria. A modular system for surface display allowed effective targeting of heterologous antigens or fragments thereof to the bacterial surface by the autotransporter domain of AIDA-I, the Escherichia coli adhesin involved in diffuse adherence. A major histocompatibility complex class II-restricted epitope, comprising amino acids 74 to 86 of the Yersinia enterocolitica heat shock protein Hsp60 (Hsp60(74-86)), was fused to the AIDA-I autotransporter domain, and the resulting fusion protein was expressed at high levels on the cell surface of E. coli and Salmonella enterica serovar Typhimurium. Colonization studies in mice vaccinated with Salmonella strains expressing AIDA-I fusion proteins demonstrated high genetic stability of the generated vaccine strain in vivo. Furthermore, a pronounced T-cell response against Yersinia Hsp60(74-86) was induced in mice vaccinated with a Salmonella vaccine strain expressing the Hsp60(74-86)-AIDA-I fusion protein. This was shown by monitoring Yersinia Hsp60-stimulated IFN-gamma secretion and proliferation of splenic T cells isolated from vaccinated mice. These results demonstrate that the surface display of antigenic determinants by the autotransporter pathway deserves special attention regarding the application in live attenuated Salmonella vaccine strains.

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.

Microbial compositional changes in broiler chicken cecal contents from birds challenged with different Salmonella vaccine candidate strains.

PubMed

Park, Si Hong; Kim, Sun Ae; Rubinelli, Peter M; Roto, Stephanie M; Ricke, Steven C

2017-05-31

Previously, we constructed and characterized the vaccine efficacy of Salmonella Typhimurium mutant strains in poultry with either inducible mviN expression (P BAD -mviN) or methionine auxotrophy (ΔΔmetRmetD). The aim of the present study was to assess potential impact of these Salmonella vaccine strains on the cecal microbiota using a next generation sequencing (NGS). The cecal microbial community obtained from unvaccinated (group 1) and vaccinated chickens (group 2, vaccinated with P BAD -mviN; group 3, vaccinated with wild type; group 4, vaccinated with ΔΔmetRmetD) were subjected to microbiome sequencing analysis with an Illumina MiSeq platform. The NGS microbiome analysis of chicken ceca revealed considerable changes in microbial composition in the presence of the different vaccine strains and exhibited detectable patterns of distinctive clustering among the respective groups (the R value of unweighted PCoA plot was 0.68). The present study indicates that different S. Typhimurium vaccine strains can differentially influence the microbiota of the ceca in terms of presence but not in the relative abundance of microbiota. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effectiveness of Pentavalent Rotavirus Vaccine Against a Diverse Range of Circulating Strains in Nicaragua.

PubMed

Patel, Manish; Pedreira, Cristina; De Oliveira, Lúcia Helena; Tate, Jacqueline; Leshem, Eyal; Mercado, Juan; Umaña, Jazmina; Balmaceda, Angel; Reyes, Martha; Kerin, Tara; McDonald, Sharla; Gentsch, Jon; Bowen, Michael D; Parashar, Umesh

2016-05-01

Because >60 rotavirus strains have been reported worldwide, concerns exist about strain replacement after the introduction of rotavirus vaccines, particularly in developing countries with diverse strains and lower efficacy. We used the case-control design in 4 hospitals in Nicaragua to assess strain-specific vaccine effectiveness (VE) of a pentavalent rotavirus vaccine (RotaTeq) against rotavirus diarrhea. Cases were identified through prospective strain surveillance with reverse transcription-polymerase chain reaction for 3 years among children hospitalized for diarrhea, and controls were children negative for rotavirus. We enrolled 1178 case-patients, 1082 (92%) with G and P typing, and 4927 controls. A different strain predominated each year with increasing age of the vaccine-eligible cohort during the study period: G2P[4] in 2008 (97%; mean age, 11.9 months), G1P[8] in 2009 (55%; mean age, 17.0 months), and G3P[8] in 2010 (78%; mean age, 17.3 months). Overall VE was 45% (95% confidence interval, 25%-59%). Regardless of the strain, VE estimates were 12%-79% lower among children aged ≥12 months relative to those 6-11 months of age. The lower VE for G3P[8] was related to the higher mean age of cases (17.3 months) compared with the G2P[4] strains (11.9 months), with a significant trend (R(2)= 0.819;P< .001) of declining effectiveness with increasing mean age of the cases. Introduction of RotaTeq did not result in sustained emergence of any particular strain in Nicaragua. Variation in strain-specific effectiveness was due to an age-related decline in effectiveness rather than differences in protection against the observed strains. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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.

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.

Real-time RT-PCR assays to differentiate wild-type group A rotavirus strains from Rotarix® and RotaTeq® vaccine strains in stool samples

PubMed Central

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. PMID:24342877

Complete Genomic Sequences of H3N8 Equine Influenza Virus Strains Used as Vaccine Strains in Japan

PubMed Central

Yamanaka, Takashi; Bannai, Hiroshi; Tsujimura, Koji; Kokado, Hiroshi

2018-01-01

ABSTRACT We sequenced the eight segments of influenza A virus strains A/equine/Ibaraki/1/2007 and A/equine/Yokohama/aq13/2010, which are strains of the Florida sublineage clades 1 and 2 of the H3N8 subtype equine influenza virus. These strains have been used as vaccine strains in Japan since 2016 in accordance with World Organization for Animal Health (OIE) recommendations. PMID:29567739

Complete Genomic Sequences of H3N8 Equine Influenza Virus Strains Used as Vaccine Strains in Japan.

PubMed

Nemoto, Manabu; Yamanaka, Takashi; Bannai, Hiroshi; Tsujimura, Koji; Kokado, Hiroshi

2018-03-22

We sequenced the eight segments of influenza A virus strains A/equine/Ibaraki/1/2007 and A/equine/Yokohama/aq13/2010, which are strains of the Florida sublineage clades 1 and 2 of the H3N8 subtype equine influenza virus. These strains have been used as vaccine strains in Japan since 2016 in accordance with World Organization for Animal Health (OIE) recommendations. Copyright © 2018 Nemoto et al.

Attenuated and Replication-Competent Vaccinia Virus Strains M65 and M101 with Distinct Biology and Immunogenicity as Potential Vaccine Candidates against Pathogens

PubMed Central

Sánchez-Sampedro, Lucas; Gómez, Carmen Elena; Mejías-Pérez, Ernesto; Pérez-Jiménez, Eva; Oliveros, Juan Carlos

2013-01-01

Replication-competent poxvirus vectors with an attenuation phenotype and with a high immunogenic capacity of the foreign expressed antigen are being pursued as novel vaccine vectors against different pathogens. In this investigation, we have examined the replication and immunogenic characteristics of two vaccinia virus (VACV) mutants, M65 and M101. These mutants were generated after 65 and 101 serial passages of persistently infected Friend erythroleukemia (FEL) cells. In cultured cells of different origins, the mutants are replication competent and have growth kinetics similar to or slightly reduced in comparison with those of the parental Western Reserve (WR) virus strain. In normal and immune-suppressed infected mice, the mutants showed different levels of attenuation and pathogenicity in comparison with WR and modified vaccinia Ankara (MVA) strains. Wide genome analysis after deep sequencing revealed selected genomic deletions and mutations in a number of viral open reading frames (ORFs). Mice immunized in a DNA prime/mutant boost regimen with viral vectors expressing the LACK (Leishmania homologue for receptors of activated C kinase) antigen of Leishmania infantum showed protection or a delay in the onset of cutaneous leishmaniasis. Protection was similar to that triggered by MVA-LACK. In immunized mice, both polyfunctional CD4+ and CD8+ T cells with an effector memory phenotype were activated by the two mutants, but the DNA-LACK/M65-LACK protocol preferentially induced CD4+ whereas DNA-LACK/M101-LACK preferentially induced CD8+ T cell responses. Altogether, our findings showed the adaptive changes of the WR genome during long-term virus-host cell interaction and how the replication competency of M65 and M101 mutants confers distinct biological properties and immunogenicity in mice compared to those of the MVA strain. These mutants could have applicability for understanding VACV biology and as potential vaccine vectors against pathogens and tumors. PMID

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

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

PubMed

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

2016-02-01

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.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Mumps vaccine failure investigation in Novosibirsk, Russia, 2002-2004.

PubMed

Atrasheuskaya, A V; Kulak, M V; Rubin, S; Ignatyev, G M

2007-07-01

The aims of this study were to estimate the importance of vaccine failure (VF) in cases of mumps during 2002-2004 in the city of Novosibirsk, Western Siberia, Russia, and to genotype the responsible virus strain. Mumps virus-specific RT-PCR testing of saliva was performed for 18 cases of mumps. Sera were tested for IgM and IgG, IgG avidity, and the ability to neutralise a panel of mumps viruses, including the Leningrad-3 mumps vaccine virus. Of the 12 patients for whom vaccination status was positively determined, 11 showed serological evidence of primary VF. Sequence analysis of virus RNA amplified from saliva revealed a genotype C2 virus in 2002, a genotype H2 virus in 2003, and both genotypes in 2004. Although several vaccinated patients were positive for mumps virus IgG at the time of first sampling, only nominal levels of neutralising antibody were detected, and these were effective in neutralising the vaccine strain, but not genotype C and H mumps virus strains. These results suggest that the majority of cases of mumps in vaccinees are caused by primary VF, defined as either a lack of seroconversion or a lack of IgG maturity, as based on avidity testing. The results also support the hypothesis that sera of low neutralising antibody titre have a limited ability to neutralise heterologous mumps virus strains, suggesting that antigenic differences between circulating and mumps vaccine virus strains may play a role in cases of breakthrough infection. Consistent with previous reports, mumps virus genotypes C and H continue to circulate in Novosibirsk.

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

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

[Comparative analysis on the complete genome sequence of mumps epidemic strain and mumps vaccine strain S79 isolated in Zhejiang province, China between year 2005 and 2010].

PubMed

Zhang, Dong-Yan; Feng, Yan; Zhong, Shu-Ling; Lu, Yi-Yu; Zhuang, Fang-Cheng; Xu, Chang-Ping

2012-03-01

To compare the differences in the complete genome sequence between mumps epidemic strain and mumps vaccine strain S79 isolated in Zhejiang province. A total of 4 mumps epidemic strains, which were separated from Zhejiang province during 2005 to 2010, named as ZJ05-1, ZJ06-3, ZJ08-1 and ZJ10-1 were selected in the study. The complete genome sequences were amplified using RT-PCR. The genetic differences between vaccine strain S79 and other genotype strains were compared; while the genetic-distance was calculated and the evolution was analyzed. The biggest difference between the 4 epidemic strains and the vaccine strain S79 was found on the membrane associated protein gene; whose average nucleotide differential number was 42.5 +/- 3.0 and the average variant ratio was 13.6%; while the mean amino acid differential number was 12.8 +/- 1.5 and the average variant ratio was 22.4%. The smallest difference among the 4 epidemic strains and the vaccine strain was found in stromatin genes, whose average nucleotide differential number was 73.8 +/- 2.5 and the average variant ratio was 5.9%; while the mean amino acid differential number was 3.0 +/- 0.8 and the average variant ratio was 0.8%. The dn/ds value of the stromatin genes of the 4 epidemic strains reached the highest, as 0.6526; but without any positive pressure (dn/ds < 1, chi2 = 0.87, P > 0.05). There were mutations happened on the known antigen epitope, as 8th amino acid of membrane associated protein genes and on the 336th and 356th amino acid of hemagglutinin/neuraminidase proteins. Compared with the vaccine strain, the glycosylation sites of ZJ05-1, ZJ06-3, ZJ08-1 and ZJ10-1 increased 1, 1, 2 and 2 respectively. The complete amino acid sequence of all strains showed that there were 17 characteristic sites found on the genotype-F mumps strain. Within the complete genome, the genetic-distance between epidemic strains and vaccine strains in Zhejiang province (0.071) was significantly larger than the genetic

Enhancement of immune response induced by DNA vaccine cocktail expressing complete LACK and TSA genes against Leishmania major.

PubMed

Ghaffarifar, Fatemeh; Jorjani, Ogholniaz; Sharifi, Zohreh; Dalimi, Abdolhossein; Hassan, Zuhair M; Tabatabaie, Fatemeh; Khoshzaban, Fariba; Hezarjaribi, Hajar Ziaei

2013-04-01

Leishmaniasis is an important disease in humans. Leishmania homologue of receptor for Activated C Kinase (LACK) and thiol specific antioxidant (TSA) as immuno-dominant antigens of Leishmania major are considered the most promising molecules for a DNA vaccine. We constructed a DNA cocktail, containing plasmids encoding LACK and TSA genes of Leishmania major and evaluated the immune response and survival rate in BALB/c mice. IgG and Interferon gamma values were noticeably increased in the immunized group with DNA cocktail vaccine, which were significantly higher than those in the single-gene vaccinated and control groups (p < 0.05) following the immunization and after challenging with Leishmania major. Interleukin 4 values were decreased in all immunized groups, but only in DNA vaccine cocktail and single-gene vaccination with pc-LACK there were statistical differences with control groups (p > 0.05). The immunized mice with the cocktail DNA vaccine presented a considerable reduction in diameter of lesion compared to other groups and a significant difference was observed (p < 0.05) in this regard. The survival time of the immunized mice with the cocktail DNA vaccine was significantly higher than that in the other groups (p < 0.05) after their being challenged with Leishmania major. The findings of this study indicated that the cocktail DNA vaccine increased the cellular response and survival rate and induced protection against infection with Leishmania in the mice. © 2012 The Authors © 2012 APMIS.

Oral Vaccination against Bubonic Plague Using a Live Avirulent Yersinia pseudotuberculosis Strain ▿

PubMed Central

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

2008-01-01

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. PMID:18505804

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

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

Glycoprotein G deficient infectious laryngotracheitis virus is a candidate attenuated vaccine.

PubMed

Devlin, Joanne M; Browning, Glenn F; Hartley, Carol A; Gilkerson, James R

2007-05-04

Infectious laryngotracheitis virus (ILTV), an alphaherpesvirus, causes respiratory disease in chickens and is currently controlled by vaccination with conventionally attenuated virus strains. These vaccines have limitations because of residual pathogenicity and reversion to virulence, suggesting that a novel vaccine strain that lacks virulence gene(s) may enhance disease control. Glycoprotein G (gG) has recently been identified as a virulence factor in ILTV. In this study the immunogenicity and relative pathogenicity of gG deficient ILTV was investigated in SPF chickens. Birds vaccinated with gG deficient ILTV were protected against clinical signs of disease following challenge with virulent ILTV and gG deficient ILTV was also shown to be less pathogenic than currently available commercial vaccine strains. Thus gG deficient ILTV appears to have potential as a vaccine candidate.

[Antigenic determination of human anti-rabies vaccine against viral street strains common in the wild animal population in Poland].

PubMed

Seroka, D

1994-01-01

The aim of the study was to compare the antigen properties of a vaccine strain with street strains isolated from various animal hosts throughout the country. Investigation was carried out using monoclonal antibodies against NC protein. Also, two tests were carried out: the modified NIH test for potency and the neutralization test using the sera of people vaccinated against rabies (PM vaccine strain). The investigated street strains were used in both tests as the challenge viruses. A suspension of these strains diluted five times made it possible to avoid extreme values of animal survival (0% or 100%) what, consequently, made calculation of the LD50 value easier. A different rabies virus serotype (EBLI virus) in the population of insectivore bats Eptesicus serotinus and antigen variants within the first serotype, having common epitopes with strains of the vaccine virus SAD B19 and the polar rabies virus, were found to be present throughout the country. The concentrated and purified vaccine containing the PM virus did not protect mice against infection with strains of viruses isolated from bats (protection index 10 and lower). For the remaining strains, depending on the animal source of their isolation, the protection index ranged from 10 to 1000 and higher. The properties neutralizing a dose of 5 i.u./ml of serum from the subject inoculated with the vaccine containing the PM strain were similar for all the investigated strains; 0,5 i.u./ml did not neutralize the strain isolated from a racoon dog.

Safety and efficacy of an attenuated Chinese QX-like infectious bronchitis virus strain as a candidate vaccine.

PubMed

Zhao, Ye; Cheng, Jin-long; Liu, Xiao-yu; Zhao, Jing; Hu, Yan-xin; Zhang, Guo-zhong

2015-10-22

Infectious bronchitis (IB) is a highly contagious respiratory and urogenital disease of chickens caused by infectious bronchitis virus (IBV). This disease is of considerable economic importance and is primarily controlled through biosecurity and immunization with live attenuated and inactivated IB vaccines of various serotypes. In the present study, we tested the safety and efficacy of an attenuated predominant Chinese QX-like IBV strain. The results revealed that the attenuated strain has a clear decrease in pathogenicity for specific-pathogen-free (SPF) chickens compared with the parent strain. Strain YN-inoculated birds had clinical signs of varying severity with 30% mortality, while the attenuated group appeared healthy, with less tissue damage. The attenuated strain also had relatively low tissue replication rates and higher antibody levels. The superior protective efficacy of the attenuated strain was observed when vaccinated birds were challenged with a homologous or heterologous field IBV strain, indicating the potential of the attenuated YN (aYN) as a vaccine. Producing a vaccine targeting the abundant serotype in China is essential to reducing the economic impact of IB on the poultry industry. Copyright © 2015 Elsevier B.V. All rights reserved.

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...

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

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.

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...

[Attenuated rabies virus, ERA strain, in cattle and dogs vaccinated with multiple doses].

PubMed

Titoli, F; Pestalozza, S; Irsara, A; Palliola, E; Frescura, T; Civardi, A

1982-01-01

Investigation on the vaccination of 18 cattle and 5 dogs against rabies is reported. Each animal received multiple doses of ERA strain vaccine intramuscularly in the gluteal or masseter region. The saliva, the brain and salivary glands of the vaccinated animals were examined to detect the presence of ERA virus using immunofluorescent test and mouse inoculation. The virus was never found in the saliva and organs of treated animals. Circulating antibodies against ERA rabies virus were detected in all vaccinated cattle and dogs.

Induction of Strain-Transcending Immunity against Plasmodium chabaudi adami Malaria with a Multiepitope DNA Vaccine

PubMed Central

Scorza, T.; Grubb, K.; Smooker, P.; Rainczuk, A.; Proll, D.; Spithill, T. W.

2005-01-01

A major goal of current malaria vaccine programs is to develop multivalent vaccines that will protect humans against the many heterologous malaria strains that circulate in endemic areas. We describe a multiepitope DNA vaccine, derived from a genomic Plasmodium chabaudi adami DS DNA expression library of 30,000 plasmids, which induces strain-transcending immunity in mice against challenge with P. c. adami DK. Segregation of this library and DNA sequence analysis identified vaccine subpools encoding open reading frames (ORFs)/peptides of >9 amino acids [aa] (the V9+ pool, 303 plasmids) and >50 aa (V50+ pool, 56 plasmids), respectively. The V9+ and V50+ plasmid vaccine subpools significantly cross-protected mice against heterologous P. c. adami DK challenge, and protection correlated with the induction of both specific gamma interferon production by splenic cells and opsonizing antibodies. Bioinformatic analysis showed that 22 of the V50+ ORFs were polypeptides conserved among three or more Plasmodium spp., 13 of which are predicted hypothetical proteins. Twenty-nine of these ORFs are orthologues of predicted Plasmodium falciparum sequences known to be expressed in the blood stage, suggesting that this vaccine pool encodes multiple blood-stage antigens. The results have implications for malaria vaccine design by providing proof-of-principle that significant strain-transcending immunity can be induced using multiepitope blood-stage DNA vaccines and suggest that both cellular responses and opsonizing antibodies are necessary for optimal protection against P. c. adami. PMID:15845504

Antibodies induced by vaccination with purified chick embryo cell culture vaccine (PCECV) cross-neutralize non-classical bat lyssavirus strains.

PubMed

Malerczyk, Claudius; Selhorst, Thomas; Tordo, Noël; Moore, Susan; Müller, Thomas

2009-08-27

Tissue-culture vaccines like purified chick embryo cell vaccine (PCECV) have been shown to provide protection against classical rabies virus (RABV) via pre-exposure or post-exposure prophylaxis. A cross-neutralization study was conducted using a panel of 100 human sera, to determine, to what extent after vaccination with PCECV protection exists against non-classical bat lyssavirus strains like European bat lyssavirus (EBLV) type 1 and 2 and Australian bat lyssavirus (ABLV). Virus neutralizing antibody (VNA) concentrations against the rabies virus variants CVS-11, ABLV, EBLV-1 and EBLV-2 were determined by using a modified rapid fluorescent focus inhibition test. For ABLV and EBLV-2, the comparison to CVS-11 revealed almost identical results (100% adequate VNA concentrations >or=0.5 IU/mL; correlation coefficient r(2)=0.69 and 0.77, respectively), while for EBLV-1 more scattering was observed (97% adequate VNA concentrations; r(2)=0.50). In conclusion, vaccination with PCECV produces adequate VNA concentrations against classical RABV as well as non-classical lyssavirus strains ABLV, EBLV-1, and EBLV-2.

Formulation and Stabilization of Francisella tularensis Live Vaccine Strain

PubMed Central

OHTAKE, SATOSHI; MARTIN, RUSSELL A.; SAXENA, ATUL; LECHUGA-BALLESTEROS, DAVID; SANTIAGO, ARACELI E; BARRY, EILEEN M.; TRUONG-LE, VU

2012-01-01

Francisella tularensis live vaccine strain (F. tularensis LVS), a promising vaccine candidate for protection against F. tularensis exposure, is a particularly thermolabile vaccine and difficult to stabilize sufficiently for storage under refrigerated conditions. Our preliminary data show that F. tularensis LVS can be stabilized in the dried state using foam drying, a modified freeze drying method, with sugar-based formulations. The process was conducted under mild drying conditions, which resulted in a good titer retention following processing. The inclusion of osmolytes in the growth media resulted in an acceleration of growth kinetics, although no change in osmotolerance was observed. The optimized F. tularensis formulation, which contained trehalose, gelatin, and Pluronic F68 demonstrated stability for approximately 1.5 weeks at 37°C (i.e., time required for the vaccine to decrease in potency by 1 log10 colony forming unit) and for 12 weeks at 25°C. At refrigerator storage condition (4°C), stabilized F. tularensis LVS vaccine exhibited no activity loss for at least 12 weeks. This stabilization method utilizes conventional freeze dryers and pharmaceutically approved stabilizers, and thus can be readily implemented at many manufacturing sites for large-scale production of stabilized vaccines. The improved heat stability of the F. tularensis LVS could mitigate risks of vaccine potency loss during long-term storage, shipping, and distribution. PMID:21491457

A effective DNA vaccine against diverse genotype J infectious hematopoietic necrosis virus strains prevalent in China

USGS Publications Warehouse

Xu, Liming; Zhao, Jingzhuang; Liu, Miao; Kurath, Gael; Ren, Guangming; LaPatra, Scott E.; Yin, Jiasheng; Liu, Hongbai; Feng, Jian; Lu, Tongyan

2017-01-01

Infectious hematopoietic necrosis virus (IHNV) is the most important pathogen threatening the aquaculture of salmonid fish in China. In this study, a DNA vaccine, designated pIHNch-G, was constructed with the glycoprotein (G) gene of a Chinese IHNV isolate SD-12 (also called Sn1203) of genotype J. The minimal dose of vaccine required, the expression of the Mx-1 gene in the muscle (vaccine delivery site) and anterior kidney, and the titers of the neutralizing antibodies produced were used to evaluate the vaccine efficacy. To assess the potential utility of the vaccine in controlling IHNV throughout China, the cross protective efficacy of the vaccine was determined by challenging fish with a broad range of IHNV strains from different geographic locations in China. A single 100 ng dose of the vaccine conferred almost full protection to rainbow trout fry (3 g) against waterborne or intraperitoneal injection challenge with IHNV strain SD-12 as early as 4 days post-vaccination (d.p.v.), and significant protection was still observed at 180 d.p.v. Intragenogroup challenges showed that the DNA vaccine provided similar protection to the fish against all the Chinese IHNV isolates tested, suggesting that the vaccine can be widely used in China. Mx-1 gene expression was significantly upregulated in the muscle tissue (vaccine delivery site) and anterior kidney in the vaccinated rainbow trout at both 4 and 7 d.p.v. Similar levels of neutralizing antibodies were determined with each of the Chinese IHNV strains at 60 and 180 d.p.v. This DNA vaccine should play an important role in the control of IHN in China.

Safety studies with the oral rabies virus vaccine strain SPBN GASGAS in the small Indian mongoose (Herpestes auropunctatus).

PubMed

Ortmann, Steffen; Vos, Ad; Kretzschmar, Antje; Walther, Nomusa; Kaiser, Christiane; Freuling, Conrad; Lojkic, Ivana; Müller, Thomas

2018-03-13

Oral vaccination of the small Indian mongoose against rabies has been suggested as a potential tool to eliminate mongoose-mediated rabies on several Caribbean islands. A recently developed oral rabies virus vaccine strain, SPBN GASGAS, has already been shown to be efficacious in this reservoir species. Since, all available oral rabies vaccines are based on replication-competent viruses and vaccine baits are distributed unsupervised in the environment, enhanced safety standards for such vaccine types are required. The results of safety studies, including overdose, repeated doses, dissemination and different routes of administration, in the target species are presented. It was shown that the construct was apathogenic, irrespective of dose and route of administration. Even when it was inoculated directly in the brain, it did not induce rabies infection. Furthermore, the vaccine strain did not spread within the target species after direct oral instillation beyond the site of entry. The vaccine strain SPBN GASGAS meets the safety requirements for live rabies virus vaccines in this target species, the small Indian mongoose.

Oral vaccination against plague using Yersinia pseudotuberculosis.

PubMed

Demeure, Christian E; Derbise, Anne; Carniel, Elisabeth

2017-04-01

Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant strains of Yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. Although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. The vaccine strategy described here is based on an oral vaccination with an attenuated strain of Yersinia pseudotuberculosis. Indeed, this species is genetically almost identical to Y. pestis, but has a much lower pathogenicity and a higher genomic stability. Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953 were performed to generate a safe and immunogenic vaccine. Genes coding for three essential virulence factors were deleted from this strain. To increase cross-species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then generated. For this, the Y. pestis caf operon, which encodes F1, was inserted first on a plasmid, and subsequently into the chromosome. The successive steps achieved to reach maximal vaccine potential are described, and how each step affected bacterial virulence and the development of a protective immune response is discussed. The final version of the vaccine, named VTnF1, provides a highly efficient and long-lasting protection against both bubonic and pneumonic plague after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist or could be engineered, we also analyzed the protection conferred by the vaccine against such strain and found that it also confers full protection against the two forms of plague. Thus, the properties of VTnF1 makes it one of the most efficient candidate vaccine for mass vaccination in tropical endemic areas as well as for populations exposed to bioterrorism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A chronicle of serologic response in commercial layer chickens to vaccination with commercial F strain Mycoplasma gallisepticum vaccine.

PubMed

Branton, S L; Leigh, S A; Purswell, J L; Evans, J D; Collier, S D; Olanrewaju, H A; Pharr, G T

2010-09-01

Vaccination of multi-age layer operations, wherein one million plus commercial layer chickens are housed, has been spurious until the development of a self-propelled, constant-speed spray vaccinator. Still, even with its use, live Mycoplasma gallisepticum (MG) vaccinations have been questionable in terms of seroconversion. Using the vaccinator as a research tool over the past 5 yr, factors have been elucidated which impact seroconversion to one live MG vaccine in particular, the F strain of MG (FMG). These factors include the type of nozzle used to spray the vaccine, the temperature of the water used to rehydrate and administer the vaccine, and the pH and osmolarity of the fluid used to apply the vaccine. In the present study, one farm was monitored for its seroconversion rates over 4 1/2 yr, during which time the FMG vaccination protocol was amended as factors were identified that enhanced seroconversion rates. The results of this study showed that implementation and inclusion of the optimized factors into the vaccination protocol for FMG enhanced seroconversion rates because they went from an initial 50%-55% positive seroconversion rate to a consistent 100% positive seroconversion rate over the 56-mo study period.

High-Resolution Melting-Curve Analysis of obg Gene to Differentiate the Temperature-Sensitive Mycoplasma synoviae Vaccine Strain MS-H from Non-Temperature-Sensitive Strains

PubMed Central

Shahid, Muhammad A.; Markham, Philip F.; Marenda, Marc S.; Agnew-Crumpton, Rebecca; Noormohammadi, Amir H.

2014-01-01

Temperature-sensitive (ts +) vaccine strain MS-H is the only live attenuated M. synoviae vaccine commercially available for use in poultry. With increasing use of this vaccine to control M. synoviae infections, differentiation of MS-H from field M. synoviae strains and from rarely occurring non-temperature-sensitive (ts –) MS-H revertants has become important, especially in countries where local strains are indistinguishable from MS-H by sequence analysis of variable lipoprotein haemagglutinin (vlhA) gene. Single nucleotide polymorphisms (SNPs) in the obg of MS-H have been found to associate with ts phenotype. In this study, four PCRs followed by high-resolution melting (HRM)-curve analysis of the regions encompassing these SNPs were developed and evaluated for their potential to differentiate MS-H from 36 M. synoviae strains/isolates. The nested-obg PCR-HRM differentiated ts + MS-H vaccine not only from field M. synoviae strains/isolates but also from ts – MS-H revertants. The mean genotype confidence percentages, 96.9±3.4 and 8.8±11.2 for ts + and ts – strains, respectively, demonstrated high differentiating power of the nested-obg PCR-HRM. Using a combination of nested-obg and obg-F3R3 PCR-HRM, 97% of the isolates/strains were typed according to their ts phenotype with all MS-H isolates typed as MS-H. A set of respiratory swabs from MS-H vaccinated specific pathogen free chickens and M. synoviae infected commercial chicken flocks were tested using obg PCR-HRM system and results were consistent with those of vlhA genotyping. The PCR-HRM system developed in this study, proved to be a rapid and reliable tool using pure M. synoviae cultures as well as direct clinical specimens. PMID:24643035

Vaccines Against Malaria

PubMed Central

Ouattara, Amed; Laurens, Matthew B.

2015-01-01

Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. PMID:25452593

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. Copyright © 2014 Elsevier B.V. All rights reserved.

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 pandemic isolates

A PfRH5-Based Vaccine Is Efficacious against Heterologous Strain Blood-Stage Plasmodium falciparum Infection in Aotus Monkeys

PubMed Central

Douglas, Alexander D.; Baldeviano, G. Christian; Lucas, Carmen M.; Lugo-Roman, Luis A.; Crosnier, Cécile; Bartholdson, S. Josefin; Diouf, Ababacar; Miura, Kazutoyo; Lambert, Lynn E.; Ventocilla, Julio A.; Leiva, Karina P.; Milne, Kathryn H.; Illingworth, Joseph J.; Spencer, Alexandra J.; Hjerrild, Kathryn A.; Alanine, Daniel G.W.; Turner, Alison V.; Moorhead, Jeromy T.; Edgel, Kimberly A.; Wu, Yimin; Long, Carole A.; Wright, Gavin J.; Lescano, Andrés G.; Draper, Simon J.

2015-01-01

Summary Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans. PMID:25590760

Providers' lack of knowledge about herpes zoster in HIV-infected patients is among barriers to herpes zoster vaccination.

PubMed

Aziz, M; Kessler, H; Huhn, G

2013-06-01

Identification of perceptions about herpes zoster (HZ) disease, vaccine effectiveness and safety, and vaccine recommendations may impact immunization practices of physicians for HIV-infected patients. A survey was used to quantify knowledge of HZ as well as determine physician immunization perceptions and practices. There were 272/1700 respondents (16%). Correct answers for the incidence of varicella zoster virus (VZV) infection in adults and incidence of HZ in HIV-infected patients were recorded by 14% and 10% of providers, respectively. Providers reported poor knowledge of the incidence of disease recurrence in HIV-infected patients (41% correct), potency of HZ vaccine (47.5% correct) and mechanism of protection against reactivation of VZV (66% correct). Most (88%) agreed that HZ was a serious disease, and 73% believed that the burden of disease made vaccination important. A majority (75%) did not vaccinate HIV patients with HZ vaccine regardless of antiretroviral therapy status. Barriers to administration included safety concerns, concern that vaccine would not prevent HZ, risk of HZ dissemination, reimbursement issues and lack of Infectious Diseases Society of America (IDSA) guidelines. Only 38% of providers agreed that CDC guidelines were clear and 50% believed that clinical trials were needed prior to use of HZ vaccine in HIV-infected patients. Education about HZ is needed among HIV providers. Providers perceived vaccination as important, but data on vaccine safety and clear guidance from the CDC on this issue are lacking.

Protection against Experimental Cryptococcosis following Vaccination with Glucan Particles Containing Cryptococcus Alkaline Extracts

PubMed Central

Lee, Chrono K.; Huang, Haibin; Shen, Zu T.; Lodge, Jennifer K.; Leszyk, John; Ostroff, Gary R.

2015-01-01

ABSTRACT A vaccine capable of protecting at-risk persons against infections due to Cryptococcus neoformans and Cryptococcus gattii could reduce the substantial global burden of human cryptococcosis. Vaccine development has been hampered though, by lack of knowledge as to which antigens are immunoprotective and the need for an effective vaccine delivery system. We made alkaline extracts from mutant cryptococcal strains that lacked capsule or chitosan. The extracts were then packaged into glucan particles (GPs), which are purified Saccharomyces cerevisiae cell walls composed primarily of β-1,3-glucans. Subcutaneous vaccination with the GP-based vaccines provided significant protection against subsequent pulmonary infection with highly virulent strains of C. neoformans and C. gattii. The alkaline extract derived from the acapsular strain was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS), and the most abundant proteins were identified. Separation of the alkaline extract by size exclusion chromatography revealed fractions that conferred protection when loaded in GP-based vaccines. Robust Th1- and Th17-biased CD4+ T cell recall responses were observed in the lungs of vaccinated and infected mice. Thus, our preclinical studies have indicated promising cryptococcal vaccine candidates in alkaline extracts delivered in GPs. Ongoing studies are directed at identifying the individual components of the extracts that confer protection and thus would be promising candidates for a human vaccine. PMID:26695631

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine in adults.

PubMed

Pépin, Stéphanie; Donazzolo, Yves; Jambrecina, Alen; Salamand, Camille; Saville, Melanie

2013-11-12

Although two antigenically distinct B strain lineages of influenza have co-circulated globally since the mid-1980s, trivalent influenza vaccines (TIVs) contain only one, resulting in frequent mismatches. This study examined the safety and immunogenicity of an inactivated quadrivalent influenza vaccine (QIV) candidate. This was a phase III, randomized, active-controlled, multicenter trial in adults during the 2011/2012 influenza season. Enrollment was stratified to include equal numbers of subjects 18-60 and >60 years of age. Subjects were randomized 5:1:1 to be vaccinated with the QIV, the licensed TIV, or an investigational TIV containing the alternate B strain lineage. Hemagglutinin inhibition antibody titers were assessed pre-vaccination and 21 days post-vaccination. 1116 subjects were vaccinated with QIV, 226 with the licensed TIV, and 223 with the investigational TIV. For all four vaccine strains, antibody responses to the QIV were non-inferior to the response to the TIV for the matched strains. For both B strains, post-vaccination antibody responses to the QIV were superior to the responses to the TIVs lacking the corresponding B strain. The QIV met all European Medicines Agency criteria for all four vaccine strains. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for the QIV and pooled TIV groups. The most commonly reported solicited reactions were injection-site pain, headache, and myalgia, and most solicited reactions were mild or moderate and appeared and resolved within 3 days of vaccination. No treatment-related serious adverse events or deaths were reported. The inactivated QIV was well tolerated without any safety concerns. For all four vaccine strains, antibody responses to the QIV were superior to the responses to TIV for the unmatched strains and non-inferior for the matched strains. QIV could therefore help address an unmet need due to mismatched B strains in previous influenza vaccines. EudraCT: 2011

Circulation of a type 1 recombinant vaccine-derived poliovirus strain in a limited area in Romania.

PubMed

Combiescu, M; Guillot, S; Persu, A; Baicus, A; Pitigoi, D; Balanant, J; Oprisan, G; Crainic, R; Delpeyroux, F; Aubert-Combiescu, A

2007-01-01

After intensive immunisation campaigns with the oral polio vaccine (OPV) as part of the Global Polio Eradication Initiative, poliomyelitis due to wild viruses has disappeared from most parts of the world, including Europe. Here, we report the characterization of a serotype 1 vaccine-derived poliovirus (VDPV) isolated from one acute flaccid paralysis (AFP) case with tetraplegia and eight healthy contacts belonging to the same small socio-cultural group having a low vaccine coverage living in a small town in Romania. The genomes of the isolated strains appeared to be tripartite type 1/type 2/type 1 vaccine intertypic recombinant genomes derived from a common ancestor strain. The presence of 1.2% nucleotide substitutions in the VP1 capsid protein coding region of most of the strains indicated a circulation time of about 14 months. These VDPVs were thermoresistant and, in transgenic mice expressing the human poliovirus receptor, appeared to have lost the attenuated phenotype. These results suggest that small populations with low vaccine coverage living in globally well-vaccinated countries can be the origin of VDPV emergence and circulation. These results reaffirm the importance of active surveillance for acute flaccid paralysis and poliovirus in both polio-free and polio-endemic countries.

Development and Characterization of an Infectious cDNA Clone of the Modified Live Virus Vaccine Strain of Equine Arteritis Virus

PubMed Central

Zhang, Jianqiang; Go, Yun Young; Huang, Chengjin M.; Meade, Barry J.; Lu, Zhengchun; Snijder, Eric J.; Timoney, Peter J.

2012-01-01

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. PMID:22739697

Acute hepatitis B caused by a vaccine-escape HBV strain in vaccinated subject: sequence analysis and therapeutic strategy.

PubMed

Luongo, Monica; Critelli, Rosina; Grottola, Antonella; Gitto, Stefano; Bernabucci, Veronica; Bevini, Mirco; Vecchi, Chiara; Montagnani, Giuliano; Villa, Erica

2015-01-01

HBV vaccine contains the 'a' determinant region, the major immune-target of antibodies (anti-HBs). Failure of immunization may be caused by vaccine-induced or spontaneous 'a' determinant surface gene mutants. Here, we evaluate the possible lack of protection by HBV vaccine, describing the case of an acute hepatitis B diagnosed in a 55-year-old Caucasian male unpaid blood donor, vaccinated against HBV. Sequencing data for preS-S region revealed multiple point mutations. Of all the substitutions found, Q129H, located in the "a" determinant region of HBsAg, can alter antigenicity, leading to mutants. This mutant may cause vaccine failure especially when associated with high viremia of infecting source. Copyright © 2014 Elsevier B.V. All rights reserved.

DNA vaccination with a plasmid encoding LACK-TSA fusion against Leishmania major infection in BALB/c mice.

PubMed

Maspi, N; Ghaffarifar, F; Sharifi, Z; Dalimi, A; Khademi, S Z

2017-12-01

Vaccination would be the most important strategy for the prevention and elimination of leishmaniasis. The aim of the present study was to compare the immune responses induced following DNA vaccination with LACK (Leishmania analogue of the receptor kinase C), TSA (Thiol-specific-antioxidant) genes alone or LACK-TSA fusion against cutaneous leishmaniasis (CL). Cellular and humoral immune responses were evaluated before and after challenge with Leishmania major (L. major). In addition, the mean lesion size was also measured from 3th week post-infection. All immunized mice showed a partial immunity characterized by higher interferon (IFN)-γ and Immunoglobulin G (IgG2a) levels compared to control groups (p<0.05). IFN-γ/ Interleukin (IL)-4 and IgG2a/IgG1 ratios demonstrated the highest IFN-γ and IgG2a levels in the group receiving LACK-TSA fusion. Mean lesion sizes reduced significantly in all immunized mice compared with control groups at 7th week post-infection (p<0.05). In addition, there was a significant reduction in mean lesion size of LACK-TSA and TSA groups than LACK group after challenge (p<0.05). In the present study, DNA immunization promoted Th1 immune response and confirmed the previous observations on immunogenicity of LACK and TSA antigens against CL. Furthermore, this study demonstrated that a bivalent vaccine can induce stronger immune responses and protection against infectious challenge with L. major.

Gallid herpesvirus 3 SB-1 strain as a recombinant viral vector for poultry vaccination.

PubMed

Sadigh, Yashar; Powers, Claire; Spiro, Simon; Pedrera, Miriam; Broadbent, Andrew; Nair, Venugopal

2018-01-01

Live herpesvirus-vectored vaccines are widely used in veterinary medicine to protect against many infectious diseases. In poultry, three strains of herpesvirus vaccines are used against Marek's disease (MD). However, of these, only the herpesvirus of turkeys (HVT) has been successfully developed and used as a recombinant vaccine vector to induce protection against other avian viral diseases such as infectious bursal disease (IBD), Newcastle disease (ND) or avian influenza (AI). Although effective when administered individually, recombinant HVT vectors have limitations when combined in multivalent vaccines. Thus there is a need for developing additional viral vectors that could be combined with HVT in inducing protection against multiple avian diseases in multivalent vaccines. Gallid herpesvirus 3 (GaHV3) strain SB-1 is widely used by the poultry industry as bivalent vaccine in combination with HVT to exploit synergistic effects against MD. Here, we report the development and application of SB-1 as a vaccine vector to express the VP2 capsid antigen of IBD virus. A VP2 expression cassette was introduced into the SB-1 genome at three intergenic locations (UL3/UL4, UL10/UL11 and UL21/UL22) using recombineering methods on the full-length pSB-1 infectious clone of the virus. We show that the recombinant SB-1 vectors expressing VP2 induced neutralising antibody responses at levels comparable to that of commercial HVT-based VAXXITEK HVT+IBD vaccine. Birds vaccinated with the experimental recombinant SB-1 vaccine were protected against clinical disease after challenge with the very virulent UK661 IBDV isolate, demonstrating its value as an efficient viral vector for developing multivalent vaccines against avian diseases.

Paradox of vaccination: is vaccination really effective against avian flu epidemics?

PubMed

Iwami, Shingo; Suzuki, Takafumi; Takeuchi, Yasuhiro

2009-01-01

Although vaccination can be a useful tool for control of avian influenza epidemics, it might engender emergence of a vaccine-resistant strain. Field and experimental studies show that some avian influenza strains acquire resistance ability against vaccination. We investigated, in the context of the emergence of a vaccine-resistant strain, whether a vaccination program can prevent the spread of infectious disease. We also investigated how losses from immunization by vaccination imposed by the resistant strain affect the spread of the disease. We designed and analyzed a deterministic compartment model illustrating transmission of vaccine-sensitive and vaccine-resistant strains during a vaccination program. We investigated how the loss of protection effectiveness impacts the program. Results show that a vaccination to prevent the spread of disease can instead spread the disease when the resistant strain is less virulent than the sensitive strain. If the loss is high, the program does not prevent the spread of the resistant strain despite a large prevalence rate of the program. The epidemic's final size can be larger than that before the vaccination program. We propose how to use poor vaccines, which have a large loss, to maximize program effects and describe various program risks, which can be estimated using available epidemiological data. We presented clear and simple concepts to elucidate vaccination program guidelines to avoid negative program effects. Using our theory, monitoring the virulence of the resistant strain and investigating the loss caused by the resistant strain better development of vaccination strategies is possible.

Knowledge assessment regarding poliomyelitis among the caregivers of children who received oral polio vaccine reveals lack of awareness of the vaccine vial monitor (VVM): Implications extending beyond polio eradication.

PubMed

Bhilwar, Meenakshi; Lal, Panna

2017-07-01

Vaccine vial monitor (VVM) is now commonly used for vaccines that are included in the National Immunization Schedule in India. It helps to indicate the viability of the vaccine and of the proper functioning of the cold chain. This is useful as it prevents health personnel from administering damaged vaccine. Studies have shown a lack of awareness of health workers regarding the use and interpretation of a VVM. The current study, undertaken among the caregivers of children who were immunized, showed that this lack of information about the VVM also exists among the caregivers. This deficiency in knowledge, both in the health workers and the caregivers, can affect the health of the child and needs urgent attention.

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.

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.

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 (C ST ) contain a unique M290K variation on the E2 protein, compared to those of primary BT cells (C BT ) or rabbit origin (C RT ) and the traditional C-strain sequences available in the GenBank database. Serum neutralization test revealed the antigenic differences between C ST and C BT or C RT . 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. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

Antibody induced by immunization with the Jeryl Lynn mumps vaccine strain effectively neutralizes a heterologous wild-type mumps virus associated with a large outbreak.

PubMed

Rubin, Steven A; Qi, Li; Audet, Susette A; Sullivan, Bradley; Carbone, Kathryn M; Bellini, William J; Rota, Paul A; Sirota, Lev; Beeler, Judy

2008-08-15

Recent mumps outbreaks in older vaccinated populations were caused primarily by genotype G viruses, which are phylogenetically distinct from the genotype A vaccine strains used in the countries affected by the outbreaks. This finding suggests that genotype A vaccine strains could have reduced efficacy against heterologous mumps viruses. The remote history of vaccination also suggests that waning immunity could have contributed to susceptibility. To examine these issues, we obtained consecutive serum samples from children at different intervals after vaccination and assayed the ability of these samples to neutralize the genotype A Jeryl Lynn mumps virus vaccine strain and a genotype G wild-type virus obtained during the mumps outbreak that occurred in the United States in 2006. Although the geometric mean neutralizing antibody titers against the genotype G virus were approximately one-half the titers measured against the vaccine strain, and although titers to both viruses decreased with time after vaccination, antibody induced by immunization with the Jeryl Lynn mumps vaccine strain effectively neutralized the outbreak-associated virus at all time points tested.

Evaluation of the use of various rat strains for immunogenic potency tests of Sabin-derived inactivated polio vaccines.

PubMed

Someya, Yuichi; Ami, Yasushi; Takai-Todaka, Reiko; Fujimoto, Akira; Haga, Kei; Murakami, Kosuke; Fujii, Yoshiki; Shirato, Haruko; Oka, Tomoichiro; Shimoike, Takashi; Katayama, Kazuhiko; Wakita, Takaji

2018-03-01

Slc:Wistar rats have been the only strain used in Japan for purpose of evaluating a national reference vaccine for the Sabin-derived inactivated polio vaccine (sIPV) and the immunogenicity of sIPV-containing products. However, following the discovery that the Slc:Wistar strain was genetically related to the Fischer 344 strain, other "real" Wistar strains, such as Crlj:WI, that are available worldwide were tested in terms of their usefulness in evaluating the immunogenicity of the past and current lots of a national reference vaccine. The response of the Crlj:WI rats against the serotype 1 of sIPV was comparable to that of the Slc:Wistar rats, while the Crlj:WI rats exhibited a higher level of response against the serotypes 2 and 3. The immunogenic potency units of a national reference vaccine determined using the Slc:Wistar rats were reproduced on tests using the Crlj:WI rats. These results indicate that a titer of the neutralizing antibody obtained in response to a given dose of sIPV cannot be directly compared between these two rat strains, but that, more importantly, the potency units are almost equivalent for the two rat strains. Copyright © 2018 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

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

Possible Impact of Yearly Childhood Vaccination With Trivalent Inactivated Influenza Vaccine (TIV) on the Immune Response to the Pandemic Strain H1N1.

PubMed

Amer, Ahdi; Fischer, Howard; Li, Xiaoming; Asmar, Basim

2016-03-01

Annual vaccination of children against seasonal influenza with trivalent inactivated influenza vaccine (TIV) has shown to be beneficial. However, this yearly practice may have unintended effect. Studies have shown that infection with wild type influenza A viruses can stimulate protective heterotypic immunity against unrelated or new influenza subtypes. We hypothesized that a consequence of yearly TIV vaccination is lack of induction of heterotypic immunity against the recent H1N1 pandemic. This was a retrospective case-control study. We reviewed the medical records of polymerase chain reaction-confirmed cases of 2009 H1N1 influenza infection in children 6 months to 18 years and a matched control group seen during the pandemic. We identified 353 polymerase chain reaction-confirmed H1N1 cases and 396 matching control subjects. Among the H1N1 group, 202/353 (57%) cases received a total of 477 doses of seasonal TIV compared with 218/396 (55%) in the control group who received a total of 435 doses. Seasonal TIV uptake was significantly higher in the H1N1 group 477/548 (87%) than in the control group, 435/532 (81%) (P = .017). Seasonal TIV uptake was significantly higher in H1N1-infected group. The finding suggests that the practice of yearly vaccination with TIV might have negatively affected the immune response against the novel pandemic H1N1 strain. Given the rarity of pandemic novel influenza viruses, and the high predictability of seasonal influenza occurrence, the practice of yearly influenza vaccination should be continued. However, the use of live attenuated intranasal vaccine, as opposed to TIV, may allow for the desirable development of a vigorous heterotypic immune response against future pandemics. © The Author(s) 2015.

Monitoring of canine parvovirus (CPV) strains detected in vaccinated puppies in Brazil.

PubMed

Castro, T X; Costa, E M; Leite, J P; Labarthe, N V; Cubel Garcia, R C N

2011-04-01

The objective of this study was to investigate, by partial sequencing of VP2 protein, the variability of CPV detected in 37 fecal samples collected from vaccinated puppies with enteritis. Laboratorial diagnosis of CPV was confirmed by HA/HI and PCR and, for sequencing analyses, two different regions of the VP2 gene were amplified by PCR. From 1995 to 2004, all strains were characterized as CPV-2a. After that, both CPV-2a and CPV-2b were detected. All CPV-2a showed a non-synonymous mutation in the residue 297 (Ser→Ala). A synonymous substitution at the AA 574 was also observed in 15/37 samples. Our findings indicate that the cases of vaccine failure are most likely not associated to the mutations detected in the sequenced regions. However, the monitoring of genotyping mutations that led to new CPV strains is essential to determinate if current vaccines will keep providing protection against all new future variants. Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

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

Evaluation of Recombinant Attenuated Salmonella Vaccine Strains for Broad Protection against Extraintestinal Pathogenic Escherichia coli.

PubMed

Maddux, Jacob T; Stromberg, Zachary R; Curtiss Iii, Roy; Mellata, Melha

2017-01-01

Antibiotic-resistant bacterial infections are difficult to treat, producing a burden on healthcare and the economy. Extraintestinal pathogenic Escherichia coli (ExPEC) strains frequently carry antibiotic resistance genes, cause infections outside of the intestine, and are causative agents of hospital-acquired infections. Developing a prevention strategy against this pathogen is challenging due to its antibiotic resistance and antigenic diversity. E. coli common pilus (ECP) is frequently found in ExPEC strains and may serve as a common antigen to induce protection against several ExPEC serotypes. In addition, live recombinant attenuated Salmonella vaccine (RASV) strains have been used to prevent Salmonella infection and can also be modified to deliver foreign antigens. Thus, the objective of this study was to design a RASV to produce ECP on its surface and assess its ability to provide protection against ExPEC infections. To constitutively display ECP in a RASV strain, we genetically engineered a vector (pYA4428) containing aspartate-β-semialdehyde dehydrogenase and E. coli ecp genes and introduced it into RASV χ9558. RASV χ9558 containing an empty vector (pYA3337) was used as a control to assess protection conferred by the RASV strain without ECP. We assessed vaccine efficacy in in vitro bacterial inhibition assays and mouse models of ExPEC-associated human infections. We found that RASV χ9558(pYA4428) synthesized the major pilin (EcpA) and tip pilus adhesin (EcpD) on the bacterial surface. Mice orally vaccinated with RASV χ9558(pYA3337) without ECP or χ9558(pYA4428) with ECP, produced anti- Salmonella LPS and anti- E. coli EcpA and EcpD IgG and IgA antibodies. RASV strains showed protective potential against some E. coli and Salmonella strains as assessed using in vitro assays. In mouse sepsis and urinary tract infection challenge models, both vaccines had significant protection in some internal organs. Overall, this work showed that RASVs can elicit an

Immune protection of chickens conferred by a vaccine consisting of attenuated strains of Salmonella Enteritidis, Typhimurium and Infantis.

PubMed

Varmuzova, Karolina; Faldynova, Marcela; Elsheimer-Matulova, Marta; Sebkova, Alena; Polansky, Ondrej; Havlickova, Hana; Sisak, Frantisek; Rychlik, Ivan

2016-10-15

The colonization of poultry with different Salmonella enterica serovars poses an issue throughout the world. In this study we therefore tested the efficacy of a vaccine consisting of attenuated strains of Salmonella enterica serovars Enteritidis, Typhimurium and Infantis against challenge with the same serovars and with S. Agona, Dublin and Hadar. We tested oral and aerosol administration of the vaccine, with or without co-administration of cecal microbiota from adult hens. The protective effect was determined by bacterial counts of the challenge strains up to week 18 of life and by characterizing the immune response using real-time PCR specific for 16 different genes. We have shown that a vaccine consisting of attenuated S. Enteritidis, S. Typhimurium and S. Infantis protected chickens against challenge with the wild type strains of the same serovars and partially protected chickens also against challenge with isolates belonging to serovars Dublin or Hadar. Aerosol vaccination was more effective at inducing systemic immunity whilst oral vaccination stimulated a local immune response in the gut. Co-administration of cecal microbiota increased the protectiveness in the intestinal tract but slightly decreased the systemic immune response. Adjusting the vaccine composition and changing the administration route therefore affects vaccine efficacy.

New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication

PubMed Central

Knowlson, Sarah; Burlison, John; Giles, Elaine; Fox, Helen; Macadam, Andrew J.; Minor, Philip D.

2015-01-01

Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization’s Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5’ non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so. PMID:26720150

New Strains Intended for the Production of Inactivated Polio Vaccine at Low-Containment After Eradication.

PubMed

Knowlson, Sarah; Burlison, John; Giles, Elaine; Fox, Helen; Macadam, Andrew J; Minor, Philip D

2015-12-01

Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization's Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5' non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.

Secreted Expression of the Cap Gene of Porcine Circovirus Type 2 in Classical Swine Fever Virus C-Strain: Potential of C-Strain Used as a Vaccine Vector.

PubMed

Zhang, Lingkai; Li, Yongfeng; Xie, Libao; Wang, Xiao; Gao, Xulei; Sun, Yuan; Qiu, Hua-Ji

2017-10-16

Bivalent vaccines based on live attenuated viruses expressing a heterologous protein are an attractive strategy to address co-infections with various pathogens in the field. Considering the excellent efficacy and safety of the lapinized live attenuated vaccine C-strain (HCLV strain) of classical swine fever virus (CSFV), we proposed that C-strain has the potential as a viral vector for developing bivalent vaccines. To this end, we generated three recombinant viruses based on C-strain, one expressing the capsid ( Cap ) gene of porcine circovirus type 2 (PCV2) with the nuclear localization signal (NLS) (rHCLV-2ACap), and the other two expressing the PCV2 Cap gene without the NLS yet containing the signal peptide of the prolactin gene (rHCLV-pspCap) or that of the ubiquitin-specific peptidase gene (rHCLV-uspCap). All the recombinant viruses exhibited phenotypes similar to those of the parental virus and produced high-level anti-CSFV neutralizing antibodies (NAbs) in rabbits. Interestingly, rHCLV-uspCap and rHCLV-pspCap, but not rHCLV-2ACap, elicited detectable anti-Cap and -PCV2 NAbs in rabbits. Taken together, our data demonstrate that C-strain can be used as a viral vector to develop bivalent vaccines.

Secreted Expression of the Cap Gene of Porcine Circovirus Type 2 in Classical Swine Fever Virus C-Strain: Potential of C-Strain Used as a Vaccine Vector

PubMed Central

Zhang, Lingkai; Li, Yongfeng; Xie, Libao; Wang, Xiao; Gao, Xulei; Sun, Yuan; Qiu, Hua-Ji

2017-01-01

Bivalent vaccines based on live attenuated viruses expressing a heterologous protein are an attractive strategy to address co-infections with various pathogens in the field. Considering the excellent efficacy and safety of the lapinized live attenuated vaccine C-strain (HCLV strain) of classical swine fever virus (CSFV), we proposed that C-strain has the potential as a viral vector for developing bivalent vaccines. To this end, we generated three recombinant viruses based on C-strain, one expressing the capsid (Cap) gene of porcine circovirus type 2 (PCV2) with the nuclear localization signal (NLS) (rHCLV-2ACap), and the other two expressing the PCV2 Cap gene without the NLS yet containing the signal peptide of the prolactin gene (rHCLV-pspCap) or that of the ubiquitin-specific peptidase gene (rHCLV-uspCap). All the recombinant viruses exhibited phenotypes similar to those of the parental virus and produced high-level anti-CSFV neutralizing antibodies (NAbs) in rabbits. Interestingly, rHCLV-uspCap and rHCLV-pspCap, but not rHCLV-2ACap, elicited detectable anti-Cap and -PCV2 NAbs in rabbits. Taken together, our data demonstrate that C-strain can be used as a viral vector to develop bivalent vaccines. PMID:29035292

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.

[The primary structure of a vaccine strain of tobacco mosaic virus V-69].

PubMed

Shiian, A N; Mil'shina, N V; Snegireva, P B; Pukhal'skiĭ, V A

1994-12-01

A random set of cDNA fragments were synthesized on genomic RNA of TMV vaccine strain V-69, using random primers and reverse transcriptase. Following synthesis of double-stranded cDNA, they were cloned into the pUC-19 plasmid; and 28 clones were sequenced (insert size 100-500 bp). High nucleotide sequence homology of V-69 (more than 95%) was shown only with tomato strain TMV-L [1]. Sequenced clones represent 54% of the genome (50% of the replicase gene, 98% of the transport protein gene, and 60% of the coat protein gene). In this genome region, 24 base substitutions were revealed, as compared to the wild-type TMV-L sequence. Six base substitutions resulted in changes in corresponding amino acid codons. No substitutions coincided with those discovered in the related TMV vaccine strain L11A [2], while two substitutions in the replicase gene were identical to those found in TMV strain Lta1 [3], which is capable of overcoming protection in tomatoes with the resistance gene Tm-1.

Phylogenetic Analysis of Theileria annulata Infected Cell Line S15 Iran Vaccine Strain.

PubMed

Habibi, Gh

2012-01-01

Bovine theileriosis results from infection with obligate intracellular protozoa of the genus Theileria. The phylogenetic relationships between two isolates of Theileria annulata, and 36 Theileria spp., as well as 6 outgroup including Babesia spp. and coccidian protozoa were analyzed using the 18S rRNA gene sequence. The target DNA segment was amplified by PCR. The PCR product was used for direct sequencing. The length of the 18S rRNA gene of all Theileria spp. involved in this study was around 1,400 bp. A phylogenetic tree was inferred based on the 18S rRNA gene sequence of the Iran and Iraq isolates, and other species of Theileria available in GenBank. In the constructed tree, Theileria annulata (Iran vaccine strain) was closely related to other T. annulata from Europe, Asia, as well as T. lestoquardi, T. parva and T. taurotragi all in one clade. Phylogenetic analyses based on small subunit ribosomal RNA gene suggested that the percent identity of the sequence of Iran vaccine strain was completely the same as Iraq sequence (100% identical), but the similarity of Iran vaccine strain with other T. annulata reported from China, Spain and Italy determined the 97.9 to 99.9% identity.

Immunogenicity and safety of a novel MMR vaccine (live, freeze-dried) containing the Edmonston-Zagreb measles strain, the Hoshino mumps strain, and the RA 27/3 rubella strain: Results of a randomized, comparative, active controlled phase III clinical trial.

PubMed

Sood, Ashwani; Mitra, Monjori; Joshi, Himanshu Arvind; Nayak, Uma Siddhartha; Siddaiah, Prashanth; Babu, T Ramesh; Mahapatro, Samarendra; Sanmukhani, Jayesh; Gupta, Gaurav; Mittal, Ravindra; Glueck, Reinhard

2017-07-03

This phase III clinical trial was conducted to evaluate the immunogenicity and safety of the single-dose and multi-dose formulations of a novel MMR vaccine (live, freeze-dried) developed by M/s Cadila Healthcare Limited, India (Cadila MMR vaccine), containing the Hoshino mumps strain, compared to that of an existing MMR vaccine (live, freeze-dried) developed by M/s Serum Institute of India Limited, India (Serum MMR vaccine). These two vaccines have similar measles and rubella strains, but different mumps strains (Hoshino in Cadila MMR vaccine, and L-Zagreb in Serum MMR vaccine). Three hundred and twenty-eight subjects of either sex, aged 15-18 months, were randomized in a 2:1 ratio to receive either the Cadila or Serum MMR vaccine. Immunogenicity assessments (IgG antibodies against measles, mumps, and rubella viruses) were done at baseline and 42 d after vaccination. Solicited (local and systemic) and unsolicited adverse events were recorded for up to 42 d following vaccination. The Cadila MMR vaccine was found to be non-inferior to the Serum MMR vaccine in terms of end-of-study proportion of subjects seropositive for anti-measles antibodies (100.0% in both groups), anti-mumps antibodies (94.5% vs. 94.0%), and anti-rubella antibodies (95.5% vs. 91.0%). Both vaccines were well tolerated by all study participants; the most common adverse event reported in both groups was fever, followed by rash. The results of this phase III clinical trial show that the novel Cadila MMR vaccine is non-inferior to the Serum MMR vaccine.

Marker vaccine strategies and candidate CSFV marker vaccines.

PubMed

Dong, Xiao-Nan; Chen, Ying-Hua

2007-01-04

Classical swine fever (CSF) is an economically important highly contagious disease of swine worldwide. Classical swine fever virus (CSFV) is its etiological agent, and the only natural hosts are domestic pigs and wild boars. Although field CSFV strains vary in the virulence, they all result in serious losses in pig industry. Highly virulent field strains generally cause acute disease and high mortality; moderately virulent field strains raise subacute or chronic infections; postnatal infection by low virulent field strains produces subclinical infection and mortality in the new-born piglets. CSFV can cross the placental barrier, and this transplacental transmission usually results in mortality of fetuses and birth of congenitally infected pigs with a late-onset disease and death. Two main strategies to control CSF epidemic are systematic prophylactic vaccination with live attenuated vaccines (such as C-strain) and non-vaccination stamping-out policy. But neither of them is satisfying enough. Marker vaccine and companion serological diagnostic test is thought to be a promising strategy for future control and eradication of CSF. During the past 15 years, various candidate marker vaccines were constructed and evaluated in the animal experiments, including recombinant chimeric vaccines, recombinant deletion vaccines, DNA vaccines, subunit vaccines and peptide vaccines. Among them, two subunit vaccines entered the large scale marker vaccine trial of EU in 1999. Although they failed to fulfil all the demands of the Scientific Veterinary Committee, they successfully induced solid immunity against CSFV in the vaccinated pigs. It can be expected that new potent marker vaccines might be commercially available and used in systematic prophylactic vaccination campaign or emergency vaccination in the next 15 years. Here, we summarized current strategies and candidate CSFV marker vaccines. These strategies and methods are also helpful for the development of new

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

Late or Lack of Vaccination Linked to Importation of Yellow Fever from Angola to China.

PubMed

Song, Rui; Guan, Shengcan; Lee, Shui Shan; Chen, Zhihai; Chen, Chen; Han, Lifen; Xu, Yanli; Li, Ang; Zeng, Hui; Ye, Hanhui; Zhang, Fujie

2018-07-17

During March and April 2016, 11 yellow fever cases were identified in China. We report epidemic and viral information for 10 of these patients, 6 of whom had been vaccinated before travel. Phylogenetic analyses suggest these viruses nested within the diversity of strains endemic to Angola, where an outbreak began in 2015.

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.

Vaccines: From Empirical Development to Rational Design

PubMed Central

Rueckert, Christine; Guzmán, Carlos A.

2012-01-01

Infectious diseases are responsible for an overwhelming number of deaths worldwide and their clinical management is often hampered by the emergence of multi-drug-resistant strains. Therefore, prevention through vaccination currently represents the best course of action to combat them. However, immune escape and evasion by pathogens often render vaccine development difficult. Furthermore, most currently available vaccines were empirically designed. In this review, we discuss why rational design of vaccines is not only desirable but also necessary. We introduce recent developments towards specifically tailored antigens, adjuvants, and delivery systems, and discuss the methodological gaps and lack of knowledge still hampering true rational vaccine design. Finally, we address the potential and limitations of different strategies and technologies for advancing vaccine development. PMID:23144616

Current challenges in the development of vaccines for pneumonic plague

PubMed Central

Smiley, Stephen T

2008-01-01

Inhalation of Yersinia pestis bacilli causes pneumonic plague, a rapidly progressing and exceptionally virulent disease. Extensively antibiotic-resistant Y. pestis strains exist and we currently lack a safe and effective pneumonic plague vaccine. These facts raise concern that Y. pestis may be exploited as a bioweapon. Here, I review the history and status of plague vaccine research and advocate that pneumonic plague vaccines should strive to prime both humoral and cellular immunity. PMID:18324890

Diagnostic tools based on minor groove binder probe technology for rapid identification of vaccinal and field strains of canine parvovirus type 2b.

PubMed

Decaro, Nicola; Martella, Vito; Elia, Gabriella; Desario, Costantina; Campolo, Marco; Buonavoglia, Domenico; Bellacicco, Anna Lucia; Tempesta, Maria; Buonavoglia, Canio

2006-12-01

TaqMan-based diagnostic tests have been developed for the identification of canine parvovirus type 2 (CPV-2) strains in the faeces of dogs with diarrhoea, including a minor groove binder (MGB) probe assay for identification of type 2-based vaccines and field strains (types 2a, 2b and 2c). Since type 2b vaccines have been licensed recently in Europe, two novel MGB assays were developed for discrimination between type 2b vaccines and field strains of CPV. Such assays have been found to be highly sensitive, specific and reproducible, allowing for simultaneous detection of type 2b vaccinal and field strains present in the same specimens. These new assays will help resolution of the diagnostic problems related to the detection of a type 2b strain in the faeces of dogs shortly after the administration of a type 2b vaccine.

A new RT-PCR assay for the identification of the predominant recombination types in 2C and 3D genomic regions of vaccine-derived poliovirus strains.

PubMed

Pliaka, V; Dedepsidis, E; Kyriakopoulou, Z; Mpirli, K; Tsakogiannis, D; Pratti, A; Levidiotou-Stefanou, S; Markoulatos, P

2010-06-01

In the post-eradication era of wild polioviruses, the only remaining sources of poliovirus infection worldwide would be the vaccine-derived polioviruses (VDPVs). As the preponderance of countries certified to be polio-free has switched from OPV (oral poliovirus vaccine) to IPV (inactivated poliovirus vaccine), importation of recombinant evolved derivatives of vaccinal strains would have serious implication for public health. To test the robustness of the proposed RT-PCR screening analysis, eleven recombinant vaccine-derived polioviruses that were characterized previously by sequencing by our group, in addition to three recently identified recombinant environmental isolates were assayed. Although the most definitive characterization of VDPVs is by genomic sequencing, in this study we describe a new, inexpensive and broadly applicable RT-PCR assay for the identification of the predominant recombination types S3/Sx in 2C and S2/Sx in 3D genomic regions respectively of VDPVs, that can be readily implemented in laboratories lacking sequencing facilities as a first approach for the early detection of vaccine-derived poliovirus (VDPVs).

Vaccines against malaria.

PubMed

Ouattara, Amed; Laurens, Matthew B

2015-03-15

Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Burden of influenza virus type B and mismatch with the flu vaccine in Spain].

PubMed

Eiros-Bouza, Jose Ma; Pérez-Rubio, Alberto

2015-02-01

Since the 80s two lineages of type B viruses are co - circulating in the world. Antigenic differences between them are important and it leads to lack of cross-reactivity. The impact on the burden of disease due to influenza B virus, poor foresight in estimating which of the two lineages of B viruses circulate in the season, and the consequent lack of immunity in case of including the wrong strain make that the availability of the quadrivalent vaccine is very useful. The aim of this paper is to analyze the past influenza seasons in Spain to assess the burden of disease, divergence between the vaccine strain and the circulating B and viral characteristics associated with type B in each seasonal epidemic. Review of all reports issued by the Influenza Surveillance System in Spain since the 2003-2004 season to 2012-2013. Over the past influenza seasons, although type A was present mostly, circulation of influenza B virus in each season was observed, even being co - dominant in some of them. In a high number of seasons the divergence between the vaccine strain and the circulating strain lineage has been observed The protective effect of influenza vaccine has varied depending on the type / subtype of influenza virus studied. The vaccine effectiveness against influenza infection by influenza B virus has varied greatly depending on the season analyzed.

Bovine herpesvirus-1: Genetic diversity of field strains from cattle with respiratory disease, genital, fetal disease and systemic neonatal disease and their relationship to vaccine strains.

PubMed

Fulton, R W; d'Offay, J M; Dubovi, E J; Eberle, R

2016-09-02

Bovine herpesvirus-1 (BoHV-1) causes disease in cattle with varied clinical forms. In the U.S. there are two BoHV1 subtypes, BoHV-1.1 and BoHV-1.2b. Control programs in North America incorporate modified live (MLV) or killed (KV) viral vaccines. However, BoHV-1 strains continue to be isolated from diseased animals or fetuses after vaccination. It is possible to differentiate BoHV-1 wild-type from MLV vaccine strains by determining their single nucleotide polymorphism (SNP) patterns through either whole-genome sequencing or PCR sequencing of genomic regions containing vaccine-defining SNPs. To determine the BoHV-1 subtype in clinical isolates and their relationship to MLV strains, 8 isolates from varied clinical disease at three different laboratories in the U.S. were sequenced and phylogenetically analyzed. Five samples were isolated within the past 5 years from New York and 3 were archived samples recovered 35 years prior from Oklahoma and Louisiana. Based on phylogenetic analysis, four of the cases appeared to be due to an MLV vaccine: 3 cases of aborted fetuses and one neonate with systemic BoHV-1 disease. One aborted fetus was from a herd with no reported history of MLV vaccination in two years. The remaining four isolates did not group with any MLV vaccines: two were associated with bovine respiratory disease, one with vulvovaginitis, and a fourth was determined to be a BoHV-1.2b respiratory isolate. Recovery of BoHV-1.1 that is very closely related to an MLV vaccine virus from a herd not receiving vaccines in an extended period prior to its isolation suggests that MLV viruses may remain latent or circulate within herds for long periods. Copyright © 2016 Elsevier B.V. All rights reserved.

Phylogenetic relationships of the HA and NA genes between vaccine and seasonal influenza A(H3N2) strains in Korea

PubMed Central

Park, Sehee; Bae, Joon-Yong; Yoo, Kirim; Cheong, Hee Jin; Noh, Ji Yun; Hong, Kyung Wook; Lemey, Philippe; Vrancken, Bram; Kim, Juwon; Nam, Misun; Yun, Soo-Hyeon; Cho, Woo In; Song, Joon Young; Kim, Woo Joo; Park, Mee Sook; Song, Jin-Won; Kee, Sun-Ho; Song, Ki-Joon; Park, Man-Seong

2017-01-01

Seasonal influenza is caused by two influenza A subtype (H1N1 and H3N2) and two influenza B lineage (Victoria and Yamagata) viruses. Of these antigenically distinct viruses, the H3N2 virus was consistently detected in substantial proportions in Korea during the 2010/11-2013/14 seasons when compared to the other viruses and appeared responsible for the influenza-like illness rate peak during the first half of the 2011/12 season. To further scrutinize possible causes for this, we investigated the evolutionary and serological relationships between the vaccine and Korean H3N2 strains during the 2011/12 season for the main antigenic determinants of influenza viruses, the hemagglutinin (HA) and neuraminidase (NA) genes. In the 2011/12 season, when the number of H3N2 cases peaked, the majority of the Korean strains did not belong to the HA clade of A/Perth/16/2009 vaccine, and no Korean strains were of this lineage in the NA segment. In a serological assay, post-vaccinated human sera exhibited much reduced hemagglutination inhibition antibody titers against the non-vaccine clade Korean H3N2 strains. Moreover, Korean strains harbored several amino acid differences in the HA antigenic sites and in the NA with respect to vaccine lineages during this season. Of these, the HA antigenic site C residues 45 and 261 and the NA residue 81 appeared to be the signatures of positive selection. In subsequent seasons, when H3N2 cases were lower, the HA and NA genes of vaccine and Korean strains were more phylogenetically related to each other. Combined, our results provide indirect support for using phylogenetic clustering patterns of the HA and possibly also the NA genes in the selection of vaccine viruses and the assessment of vaccine effectiveness. PMID:28257427

Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model.

PubMed

Cameron, Mark J; Kelvin, Alyson A; Leon, Alberto J; Cameron, Cheryl M; Ran, Longsi; Xu, Luoling; Chu, Yong-Kyu; Danesh, Ali; Fang, Yuan; Li, Qianjun; Anderson, Austin; Couch, Ronald C; Paquette, Stephane G; Fomukong, Ndingsa G; Kistner, Otfried; Lauchart, Manfred; Rowe, Thomas; Harrod, Kevin S; Jonsson, Colleen B; Kelvin, David J

2012-01-01

In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)(3)-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.

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...

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 ...

Efficacy, Safety, and Interactions of a Live Infectious Bursal Disease Virus Vaccine for Chickens Based on Strain IBD V877.

PubMed

Geerligs, Harm J; Ons, Ellen; Boelm, Gert Jan; Vancraeynest, Dieter

2015-03-01

Infectious bursal disease (IBD) is a highly contagious disease in young chickens which can result in high morbidity and mortality and also in great economic losses. The main target for the virus is the lymphoid tissue with a special predilection for the bursa of Fabricius. Several vaccines are available to control the disease. Intermediate plus vaccines are used in chickens with high maternal antibody titers which face high infection pressure. An example of an intermediate plus vaccine is a live vaccine based on IBD strain V877. The results of an efficacy study in commercial broilers with different levels of maternally derived antibodies (MDA) showed that the V877-based IBD vaccine can break through maternal antibody titers of higher than 1100 as determined by an IBD ELISA. The safety of the vaccine was demonstrated in a study in which specific-pathogen-free (SPF) chickens were vaccinated with a tenfold dose of the vaccine strain and a tenfold dose of the vaccine strain after five back passages in SPF chickens. The vaccine virus caused lesions, as could be expected for an intermediate plus vaccine, but the scores were not much higher than the maximal scores allowed for mild IBD vaccines in the European Pharmacopoeia, and reversion to virulence was absent. In studies in SPF chickens, there were no negative impacts by the IBD V877 vaccine on the efficacy of a live QX-like IB vaccine and a live Newcastle disease La Sota vaccine in vaccination challenge studies, although the IBD vaccine had a negative effect on the antibody response generated by the QX-like IB vaccine. It is concluded that the IBD V877 vaccine has the capacity to break through high levels of MDA, has a satisfactory safety profile, and interactions with other live vaccines are limited. In order to limit bursal lesions after vaccination it is recommended to confirm the presence of MDA before vaccinating with the V877 vaccine.

Immunogenicity, reactogenicity, and safety of a P1.7b,4 strain-specific serogroup B meningococcal vaccine given to preteens.

PubMed

Hosking, Jamie; Rasanathan, Kumanan; Mow, Florina Chan; Jackson, Catherine; Martin, Diana; O'Hallahan, Jane; Oster, Philipp; Ypma, Ellen; Reid, Stewart; Aaberge, Ingeborg; Crengle, Sue; Stewart, Joanna; Lennon, Diana

2007-11-01

New Zealand (NZ) has experienced a Neisseria meningitidis serogroup B epidemic since 1991. MeNZB, a strain-specific outer membrane vesicle vaccine made using an NZ epidemic strain isolate, NZ98/254 (B:4:P1.7b,4), from two manufacturing sites, the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (CV; now Novartis), was evaluated for safety, immunogenicity, and reactogenicity in this observer-blind trial with 8- to 12-year-old children. In year 1, cohort A (n = 302) was randomized 4:1 for receipt of NIPH-MeNZB or MenBvac (Norwegian parent vaccine strain 44/76; B:15:P1.7,16). In year 2, cohort B (n = 313) was randomized 4:1 for receipt of CV-MeNZB or NIPH-MeNZB. Participants all received three vaccinations 6 weeks apart. Local and systemic reactions were monitored for 7 days. Seroresponse was defined as a fourfold or greater rise in the serum bactericidal antibody titer from the baseline titer as measured by a serum bactericidal assay. Those with baseline titers of <1:4 required titers of >/=1:8 to serorespond. Intention-to-treat (ITT) and per protocol (PP) analyses are presented. In cohort A, 74% (ITT) and 73% (PP) of NIPH-MeNZB recipients demonstrated seroresponses against NZ98/254 after three doses, versus 32% (ITT and PP) of MenBvac recipients. In cohort B, seroresponses against NZ98/254 after three doses occurred in 79% (ITT and PP) of CV-MeNZB versus 75% (ITT) and 76% (PP) of NIPH-MeNZB recipients. Vaccines were tolerable, with no vaccine-related serious adverse events. In conclusion, the NZ strain meningococcal B vaccine (MeNZB) from either manufacturing site was immunogenic against New Zealand epidemic vaccine strain meningococci with no safety concerns when given in three doses to these 8- to 12-year-old children.

Efficacy of lyophilised C-strain vaccine after oral immunisation of domestic pigs and wild boar against classical swine fever: first results.

PubMed

Faust, A; Lange, E; Kaden, V

2007-11-01

The aim of this study was to evaluate the efficacy of lyophilised C-strain vaccine in domestic pigs and wild boar after oral application. A new spherical bait form (diameter 3 cm) containing lyophilised vaccine virus and the recent vaccine baits were used for animal experiments. Four vaccination groups were established in experiment 1 (group 1: recent liquid bait vaccine; group 2: spherical baits containing one dose of the lyophilised vaccine; groups 3 (domestic pigs) and 4 (wild boar): spherical baits containing two doses of the lyophilised vaccine) and two groups in experiment 2 (group 1: recent liquid bait vaccine; group 2: spherical baits with two doses of the lyophilised vaccine). Challenge was carried out with the highly virulent virus strain "Alfort 187" (using 100 TCID50 in the first and 1.000 TCID50 in the second experiment). Our results showed that the animals vaccinated with lyophilised C-strain vaccine developed high neutralising antibody titres comparable to those obtained after vaccination with the recent bait vaccine. All pigs which picked up the baits remained healthy after challenge. Neither clinical symptoms nor viremia or virus shedding were observed after infection except in one pig (group 2, experiment 2) which had not consumed the vaccine bait. The surviving domestic pigs and wild boar were tested negative for CSFV and viral RNA at the end of the study. This result demonstrates that lyophilised vaccine may become an effective vaccine formulation for oral immunisation of wild boar against CSF in the near future.

A multiplex reverse transcription-nested polymerase chain reaction for detection and differentiation of wild-type and vaccine strains of canine distemper virus

PubMed Central

2010-01-01

A multiplex reverse transcription-nested polymerase chain reaction (RT-nPCR) method was developed for the detection and differentiation of wild-type and vaccine strains of canine distemper virus (CDV). A pair of primers (P1 and P4) specific for CDV corresponding to the highly conserved region of the CDV genome were used as a common primer pair in the first-round PCR of the nested PCR. Primers P2 specific for CDV wild-type strains, were used as the forward primer together with the common reverse primer P4 in the second round of nested PCR. Primers P3, P5 specific for CDV wild-type strain or vaccine strain, were used as the forward primer together with the common reverse primer P4+P6 in the second round of nested PCR. A fragment of 177 bp was amplified from vaccine strain genomic RNA, and a fragment of 247 bp from wild-type strain genomic RNA in the RT-nPCR, and two fragments of 247 bp and 177 bp were amplified from the mixed samples of vaccine and wild-type strains. No amplification was achieved for uninfected cells, or cells infected with Newcastle disease virus (NDV), canine parvovirus (CPV), canine coronavirus (CCV), rabies virus (RV), or canine adenovirus (CAV). The RT-nPCR method was used to detect 30 field samples suspected of canine distemper from Heilongjiang and Jilin Provinces, and 51 samples in Shandong province. As a result of 30 samples, were found to be wild-type-like, and 5 to be vaccine-strain-like. The RT-nPCR method can be used to effectively detect and differentiate wild-type CDV-infected dogs from dogs vaccinated with CDV vaccine, and thus can be used in clinical detection and epidemiological surveillance. PMID:20433759

Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain

PubMed Central

Steel, John; Lowen, Anice C.; Wang, Taia T.; Yondola, Mark; Gao, Qinshan; Haye, Kester; García-Sastre, Adolfo; Palese, Peter

2010-01-01

ABSTRACT Although highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine. PMID:20689752

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.

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.

Efficacy of an inactivated bivalent vaccine against the prevalent strains of Newcastle disease and H9N2 avian influenza.

PubMed

Zhao, Jing; Yang, Huiming; Xu, Hongjun; Ma, Zengbin; Zhang, Guozhong

2017-03-16

Newcastle disease (ND) and avian influenza subtype H9N2 (H9N2 AI) are two of the most important diseases of poultry, causing severe economic losses in the global poultry industry. Vaccination is an effective way to prevent and control the spread of ND virus (NDV) and H9N2 AI virus (AIV), but the antigenic differences between the current circulating strains and the vaccine strains might account for recent ND and H9N2 AI outbreaks in vaccinated poultry flocks. We developed an inactivated bivalent H9N2 and NDV vaccine based on the current prevalent strains of H9N2 AIV and NDV in China and evaluated its efficacy in chickens in this study. The results indicated that the inactivated bivalent vaccine could induce a fast antibody response in vaccinated chickens. The hemagglutination inhibition (HI) titer in the sera increased rapidly, and the highest HI titer was observed at 4 weeks post-vaccination (wpv) with a mean titre of 8.6 log 2 for NDV and 9.5 log 2 for H9N2. Up until 15 wpv, HI titers were still detectable at a high level of over 6 log 2 . The immunized chickens showed no signs of disease after challenge at 3 wpv with the prevalent strains of NDV and H9N2 AIV isolated in 2012-2014. Moreover, viral shedding was completely inhibited in vaccinated chickens after challenge with H9N2 AIV and inhibited by at least 90% with NDV compared to the controls at 5dpc. Our findings suggest that the inactivated NDV and H9N2 vaccine induces a fast and strong antibody response in vaccinated chickens and is efficacious in poultry against NDVs and H9N2 AIVs.

Genetic and antigenic relationship of foot-and-mouth disease virus serotype O isolates with the vaccine strain O1/BFS.

PubMed

Xu, Wanhong; Zhang, Zhidong; Nfon, Charles; Yang, Ming

2018-05-15

Foot-and-mouth disease serotype O viruses (FMDV/O) are responsible for the most outbreaks in FMD endemic countries. O1/BFS is one of the recommended FMD/O vaccine strains by World Reference Laboratory for FMD. In the current study, FMDV/O1 BFS vaccine strain and serotype O field isolates (45) were analyzed phylogenetically and antigenically to gain more insight into the genetic and antigenic characteristics of the vaccine strain and field isolates. O1/BFS showed similarity with 89% of the field isolates using a virus neutralization test (VNT). The P1 region encoding the FMDV capsid was sequenced and analysed for 46 strains of FMDV/O. Phylogenetic analysis showed these viruses originated from five continents and covered eight of 11 reported topotypes. Five isolates that demonstrated low antigenic similarities with O1/BFS were analyzed for their antigenic variation at the known neutralizing antigenic sites. Three of the five isolates demonstrated unique amino acid substitutions at various antigenic sites. No unique amino acid substitutions were observed for the other two unmatched isolates. Positively selected residues were identified on the surface of the FMD virus capsid supporting that it is important to continuously monitor field isolates for their antigenic and phenotypic changes. In conclusion, the vaccine strain O1/BFS is likely to confer protection against 89% of the 45 FMDV/O isolates based on VNT. Thus O1/BFS vaccine strain is still suitable for use in global FMD serotype O outbreak control. Combining data from phylogenetic, molecular and antigenic analysis can provide improvements in the process of vaccine selection. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Vaccination against Salmonella Infection: the Mucosal Way.

PubMed

Gayet, Rémi; Bioley, Gilles; Rochereau, Nicolas; Paul, Stéphane; Corthésy, Blaise

2017-09-01

Salmonella enterica subspecies enterica includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated morbidity and mortality, together with an increased emergence of multidrug-resistant strains, is a current global health issue that has prompted the development of vaccination strategies that confer protection against most serovars. Currently available systemic vaccine approaches have major limitations, including a reduced effectiveness in young children and a lack of cross-protection among different strains. Having studied host-pathogen interactions, microbiologists and immunologists argue in favor of topical gastrointestinal administration for improvement in vaccine efficacy. Here, recent advances in this field are summarized, including mechanisms of bacterial uptake at the intestinal epithelium, the assessment of protective host immunity, and improved animal models that closely mimic infection in humans. The pros and cons of existing vaccines are presented, along with recent progress made with novel formulations. Finally, new candidate antigens and their relevance in the refined design of anti- Salmonella vaccines are discussed, along with antigen vectorization strategies such as nanoparticles or secretory immunoglobulins, with a focus on potentiating mucosal vaccine efficacy. Copyright © 2017 American Society for Microbiology.

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

Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in adults.

PubMed

Gorse, Geoffrey J; Falsey, Ann R; Ozol-Godfrey, Ayca; Landolfi, Victoria; Tsang, Peter H

2015-02-25

An intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone(®) Intradermal, Sanofi Pasteur, Swiftwater, PA) has been available in the US since the 2011/2012 influenza season for adults aged 18-64 years. This study examined whether adding a second B-lineage strain affects immunogenicity and safety. This randomized, double-blind, multicentre trial evaluated the immunogenicity and safety of an intradermal quadrivalent split-virion influenza vaccine (IIV4-ID) in adults 18-64 years of age in the US during the 2012-2013 influenza season. Participants were randomized 2:1:1 to receive a single injection of IIV4-ID, licensed IIV3-ID, or an investigational IIV3-ID containing the alternate B-lineage strain. Haemagglutination inhibition antibody titres were assessed in two-thirds of participants before vaccination and 28 days after vaccination. 1672 participants were vaccinated with IIV4-ID, 837 with licensed IIV3-ID, and 846 with an investigational IIV3-ID. For all four vaccine strains, antibody responses to IIV4-ID were statistically non-inferior to the response to the IIV3-ID vaccines containing the matched strains. For both B strains, post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to IIV3-ID lacking the corresponding B strain. Adverse events were similar for IIV4-ID and IIV3-ID. The most commonly reported solicited reactions were pain, pruritus, myalgia, headache, and malaise; and most were grade 1 or 2 and appeared and resolved within 3 days of vaccination. IIV4-ID was statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction. Antibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and matched B strains and superior for the unmatched B strains. IIV4-ID was well tolerated without any safety concerns. IIV4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines

Generation by Reverse Genetics of an Effective, Stable, Live-Attenuated Newcastle Disease Virus Vaccine Based on a Currently Circulating, Highly Virulent Indonesian Strain

PubMed Central

Xiao, Sa; Nayak, Baibaswata; Samuel, Arthur; Paldurai, Anandan; Kanabagattebasavarajappa, Mallikarjuna; Prajitno, Teguh Y.; Bharoto, Eny E.; Collins, Peter L.; Samal, Siba K.

2012-01-01

Newcastle disease virus (NDV) can cause severe disease in chickens. Although NDV vaccines exist, there are frequent reports of outbreaks in vaccinated chickens. During 2009–2010, despite intense vaccination, NDV caused major outbreaks among commercial poultry farms in Indonesia. These outbreaks raised concern regarding the protective immunity of current vaccines against circulating virulent strains in Indonesia. In this study, we investigated whether a recombinant attenuated Indonesian NDV strain could provide better protection against prevalent Indonesian viruses. A reverse genetics system for the highly virulent NDV strain Banjarmasin/010/10 (Ban/010) isolated in Indonesia in 2010 was constructed. The Ban/010 virus is classified in genotype VII of class II NDV, which is genetically distinct from the commercial vaccine strains B1 and LaSota, which belong to genotype II, and shares only 89 and 87% amino acid identity for the protective antigens F and HN, respectively. A mutant virus, named Ban/AF, was developed in which the virulent F protein cleavage site motif “RRQKR↓F” was modified to an avirulent motif “GRQGR↓L” by three amino acid substitutions (underlined). The Ban/AF vaccine virus did not produce syncytia or plaques in cell culture, even in the presence of added protease. Pathogenicity tests showed that Ban/AF was completely avirulent. Ban/AF replicated efficiently during 10 consecutive passages in chickens and remained genetically stable. Serological analysis showed that Ban/AF induced higher neutralization and hemagglutination inhibition antibody titers against the prevalent viruses than the commercial vaccines B1 or LaSota. Both Ban/AF and commercial vaccines provided protection against clinical disease and mortality after challenge with virulent NDV strain Ban/010 (genotype VII) or GB Texas (genotype II). However, Ban/AF significantly reduced challenge virus shedding from the vaccinated birds compared to B1 vaccine. These results suggest

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

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

PubMed

Hatcher, Christopher L; Mott, Tiffany M; Muruato, Laura A; Sbrana, Elena; Torres, Alfredo G

2016-08-01

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. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

[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

Utility of a stressed-SNP real-time PCR assay for the rapid identification of measles vaccine strain in patient samples.

PubMed

Tran, Thomas; Kostecki, Renata; Catton, Michael; Druce, Julian

2018-05-09

Rapid differentiation of wild-type measles virus from measles vaccine strains is crucial during a measles outbreak and in a measles elimination setting. A real-time RT-PCR for the rapid detection of measles vaccine strains was developed with high specificity and greater sensitivity than when compared to traditional measles genotyping methods. The "stressed" minor grove binder TaqMan probe design approach achieves specificity to vaccine strains only, without compromising sensitivity. This assay has proven to be extremely useful in outbreak settings, without requiring sequence genotyping, for over 4 years at the Regional Measles Reference Laboratory for the Western Pacific Region. Copyright © 2018 Tran et al.

Vaccines against biologic agents: uses and developments.

PubMed

Ales, Noel C; Katial, Rohit K

2004-03-01

Although the Geneva protocol that prohibits the use of chemical and biologic weapons was ratified in 1925, many countries failed to accept this protocol: others stipulated retaliation, and some, like the United States, did not ratify the protocol for decades. This delay allowed the continued development of chemical and biologic agents. Members of the health care community are responsible for determining the best way to protect society from the potentially devastating effects of these biologic agents. Ideally,these diseases would be prevented from ever developing into systemic illnesses. In the past, vaccination has been a successful means of eradicating disease. Vaccines remain a hopeful therapy for the future, but time is short,and there are many obstacles.Information regarding bioterrorism agents and their treatments comes mainly from dated data or from in vitro or animal studies that may not apply to human treatment and disease. Additionally, the current threat of bioterrorism does not allow enough time for accurate, well-designed,controlled studies in humans before the release of investigational vaccines. Furthermore, some human studies would not be safe or ethical. Finally,many members of society suffer from illnesses that would put them at high risk to receive prophylactic vaccination. It is therefore naive to believe that vaccines would be the ultimate protection from these agents. In addition to vaccine development, there must be concurrent investigations into disease management and treatment. Even in instances in which vaccination is known to be an effective means of disease protection. biologic agents may be presented in a manner that renders vaccines ineffective. Virulent strains of organisms may be used, more than one organism may be used in tandem to increase virulence, and strains may be selected for antibiotic and vaccine resistance. Genetically engineered strains may use virulence factors other than those targeted in vaccines, and high

Oral Modeling of an Adenovirus-Based Quadrivalent Influenza Vaccine in Ferrets and Mice.

PubMed

Scallan, Ciaran D; Lindbloom, Jonathan D; Tucker, Sean N

2016-06-01

Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required. In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets. We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine. The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines. Vaxart, Inc.

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

Vaccination with killed whole-cells of Escherichia coli O157:H7 hha mutant emulsified with an adjuvant induced vaccine strain-specific serum antibodies and reduced E. coli O157:H7 fecal shedding in cattle.

PubMed

Sharma, Vijay K; Schaut, Robert G; Loving, Crystal L

2018-06-01

Escherichia coli O157:H7 (O157) can cause from a mild diarrheal illness to hemorrhagic colitis and hemolytic uremic syndrome in humans. Cattle are the primary reservoir for O157 and fecal shedding of O157 by these animals is a major risk factor in contamination of cattle hides and carcasses at slaughter. Vaccination is an important strategy to reduce fecal shedding of O157 in cattle. In this study, we evaluated the immunogenicity and efficacy of an inactivated vaccine strain of O157 formulated with an adjuvant. This vaccine strain was deleted of the hha gene enabling high level expression of the locus of enterocyte effacement (LEE) encoded proteins required for O157 colonization in cattle. The inactivated vaccine strain emulsified with the adjuvant or suspended in the phosphate-buffered saline (PBS) was injected in the neck muscles of two groups of weaned calves followed by a booster three weeks later with the corresponding formulation. Animals in groups 3 and 4 were injected similarly with the adjuvant and PBS, respectively. All animals were orally inoculated three weeks post-booster vaccination with a live culture of O157. The animals vaccinated with the adjuvanted vaccine showed higher serum antibody titers to the vaccine strain and shed O157 for a shorter duration and at lower numbers compared to the animals vaccinated with the non-adjuvanted vaccine, adjuvant-only, or PBS. Western blotting of the vaccine strain lysates showed higher immunoreactivity of serum IgG in vaccinated animals to several O157-specific proteins and lipopolysaccharides (LPS). The vaccination induced IgG showed specificity to LEE-encoded proteins and outer membrane LPS as LEE and waaL deletion mutants, unable to produce LEE proteins and synthesize high molecular weight LPS, respectively, yielded significantly lower antibody titers compared to the parent vaccine strain. The positive reactivity of the immune serum was also observed for purified LEE-encoded proteins EspA and EspB. In

Attenuation of the goose parvovirus strain B. Laboratory and field trials of the attenuated mutant for vaccination against Derzsy's disease.

PubMed

Kisary, J; Derzsy, D; Meszaros, J

1978-07-01

Serial transfer of the goose parvovirus strain B, causal agent of Derzsy's gosling disease, in cultured goose-embryo fibroblast (GEF) resulted in a mutant (designated as Bav) apathogenic for both goose embryos and susceptible goslings. Goose embryos inoculated with the 38th or higher passages of strain B survived the infection, although the virus replicated in their organs. Susceptible goslings survived challenge with the Bav strain without showing symptoms, and developed normally. Only 4.2% of gosling progeny of parents vaccinated twice with strain Bav died after challenge with the virulent strain B goose parvovirus compared with 95% of gosling progeny of unvaccinated parents. Progeny of vaccinated and unvaccinated geese were placed on a farm on which Derzsy's disease was present. During the first month of life mortality was 7.7% in the progeny of vaccinated geese compared with 59.8% in the progeny of the unvaccinated geese. At 8 weeks of age the mean weight of the vaccinated goslings was 20% greater than for the unvaccinated goslings. These results indicate that the attenuated apathogenic Bav mutant is suitable for the immunisation of layers to protect their progeny by passive immunisation against Derzsy's disease.

Yersinia pestis caf1 variants and the limits of plague vaccine protection.

PubMed

Quenee, Lauriane E; Cornelius, Claire A; Ciletti, Nancy A; Elli, Derek; Schneewind, Olaf

2008-05-01

Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.

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

Different levels of immunogenicity of two strains of Fowlpox virus as recombinant vaccine vectors eliciting T-cell responses in heterologous prime-boost vaccination strategies.

PubMed

Cottingham, Matthew G; van Maurik, Andre; Zago, Manola; Newton, Angela T; Anderson, Richard J; Howard, M Keith; Schneider, Jörg; Skinner, Michael A

2006-07-01

The FP9 strain of F has been described as a more immunogenic recombinant vaccine vector than the Webster FPV-M (FPW) strain (R. J. Anderson et al., J. Immunol. 172:3094-3100, 2004). This study expands the comparison to include two separate recombinant antigens and multiple, rather than single, independent viral clones derived from the two strains. Dual-poxvirus heterologous prime-boost vaccination regimens using individual clones of recombinant FP9 or FPW in combination with recombinant modified V Ankara expressing the same antigen were evaluated for their ability to elicit T-cell responses against recombinant antigens from Plasmodium berghei (circumsporozoite protein) or human immunodeficiency virus type 1 (a Gag-Pol-Nef fusion protein). Gamma interferon enzyme-linked immunospot assay and fluorescence-activated cell sorting assays of the responses to specific epitopes confirmed the approximately twofold-greater cellular immunogenicity of FP9 compared to FPW, when given as the priming or boosting immunization. Equality of transgene expression in mouse cells infected with the two strains in vitro was verified by Western blotting. Directed partial sequence analysis and PCR analysis of FPW and comparison to available whole-genome sequences revealed that many loci that are mutated in the highly attenuated and culture-adapted FP9 strain are wild type in FPW, including the seven multikilobase deletions. These "passage-specific" alterations are hypothesized to be involved in determining the immunogenicity of fowlpox virus as a recombinant vaccine vector.

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

A novel rapid direct haemagglutination-inhibition assay for measurements of humoral immune response against non-haemagglutinating Fowlpox virus strains in vaccinated chickens.

PubMed

Wambura, Philemon N; Mzula, Alexanda

2017-10-01

Fowlpox (FP) is a serious disease in chickens caused by Fowlpox virus (FPV). One method currently used to control FPV is vaccination followed by confirmation that antibody titres are protective using the indirect haemagglutination assay (IHA). The direct haemagglutination inhibition (HI) assay is not done because most FPV strains do not agglutinate chicken red blood cells (RBCs). A novel FPV strain TPV-1 which agglutinates chicken RBCs was discovered recently and enabled a direct HI assay to be conducted using homologous sera. This study is therefore aimed at assessing the direct HI assay using a recently discovered novel haemagglutinating FPV strain TPV-1 in chickens vaccinated with a commercial vaccine containing a non-haemagglutinating FPV.Chicks vaccinated with FPV at 1 day-old had antibody geometric mean titres (GMT) of log 2 3.7 at 7 days after vaccination and log 2 8.0 at 28 days after vaccination when tested in the direct HI. Chickens vaccinated at 6 weeks-old had antibody geometric mean titres (GMT) of log 2 5.0 at 7 days after vaccination and log 2 8.4 at 28 days after vaccination when tested in the direct HI. The GMT recorded 28 days after vaccination was slightly higher in chickens vaccinated at 6-week-old than in chicks vaccinated at one-day-old. However, this difference was not significant (P > 0.05). All vaccinated chickens showed "takes". No antibody response to FPV and "takes" were detected in unvaccinated chickens (GMT < 1). There was a slightly higher GMT in chickens of all ages throughout the observation period when the standard assay, the passive (indirect) haemagglutination was used (Overall GMT reached log 2 9.3 ±.0.3 on day 28). However, the difference between the two assays was not significant (P > 0.05). These findings indicate that a simple and rapid direct HI assay using the FPV TPV-1 strain as antigen may be used to measure antibody levels in chickens vaccinated with non-haemagglutinating strains of FPV, and that the titres are

Clinical development of a novel inactivated poliomyelitis vaccine based on attenuated Sabin poliovirus strains.

PubMed

Verdijk, Pauline; Rots, Nynke Y; Bakker, Wilfried A M

2011-05-01

Following achievement of polio eradication, the routine use of all live-attenuated oral poliovirus vaccines should be discontinued. However, the costs per vaccine dose for the alternative inactivated poliovirus vaccine (IPV) are significantly higher and the current production capacity is not sufficient for worldwide distribution of the vaccine. In order to achieve cost-prize reduction and improve affordability, IPV production processes and dose-sparing strategies should be developed to facilitate local manufacture at a relatively lower cost. The use of attenuated Sabin instead of wild-type polio strains will provide additional safety during vaccine production and permits production in low-cost settings. Sabin-IPV is under development by several manufacturers. This article gives an overview of results from clinical trials with Sabin-IPV and discusses the requirements and challenges in the clinical development of this novel IPV.

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. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immunogenicity, Reactogenicity, and Safety of a P1.7b,4 Strain-Specific Serogroup B Meningococcal Vaccine Given to Preteens▿

PubMed Central

Hosking, Jamie; Rasanathan, Kumanan; Mow, Florina Chan; Jackson, Catherine; Martin, Diana; O'Hallahan, Jane; Oster, Philipp; Ypma, Ellen; Reid, Stewart; Aaberge, Ingeborg; Crengle, Sue; Stewart, Joanna; Lennon, Diana

2007-01-01

New Zealand (NZ) has experienced a Neisseria meningitidis serogroup B epidemic since 1991. MeNZB, a strain-specific outer membrane vesicle vaccine made using an NZ epidemic strain isolate, NZ98/254 (B:4:P1.7b,4), from two manufacturing sites, the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (CV; now Novartis), was evaluated for safety, immunogenicity, and reactogenicity in this observer-blind trial with 8- to 12-year-old children. In year 1, cohort A (n = 302) was randomized 4:1 for receipt of NIPH-MeNZB or MenBvac (Norwegian parent vaccine strain 44/76; B:15:P1.7,16). In year 2, cohort B (n = 313) was randomized 4:1 for receipt of CV-MeNZB or NIPH-MeNZB. Participants all received three vaccinations 6 weeks apart. Local and systemic reactions were monitored for 7 days. Seroresponse was defined as a fourfold or greater rise in the serum bactericidal antibody titer from the baseline titer as measured by a serum bactericidal assay. Those with baseline titers of <1:4 required titers of ≥1:8 to serorespond. Intention-to-treat (ITT) and per protocol (PP) analyses are presented. In cohort A, 74% (ITT) and 73% (PP) of NIPH-MeNZB recipients demonstrated seroresponses against NZ98/254 after three doses, versus 32% (ITT and PP) of MenBvac recipients. In cohort B, seroresponses against NZ98/254 after three doses occurred in 79% (ITT and PP) of CV-MeNZB versus 75% (ITT) and 76% (PP) of NIPH-MeNZB recipients. Vaccines were tolerable, with no vaccine-related serious adverse events. In conclusion, the NZ strain meningococcal B vaccine (MeNZB) from either manufacturing site was immunogenic against New Zealand epidemic vaccine strain meningococci with no safety concerns when given in three doses to these 8- to 12-year-old children. PMID:17898183

Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: A randomized, placebo-controlled trial.

PubMed

Mcbride, William J H; Abhayaratna, Walter P; Barr, Ian; Booy, Robert; Carapetis, Jonathan; Carson, Simon; De Looze, Ferdinandus; Ellis-Pegler, Rod; Heron, Leon; Karrasch, Jeff; Marshall, Helen; Mcvernon, Jodie; Nolan, Terry; Rawlinson, William; Reid, Jim; Richmond, Peter; Shakib, Sepehr; Basser, Russell L; Hartel, Gunter F; Lai, Michael H; Rockman, Steven; Greenberg, Michael E

2016-09-22

Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. This observer-blind, randomized, placebo-controlled study enrolled adults aged 18-64years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. Over a study period of 2years, 15,044 participants were enrolled (mean age±standard deviation: 35.5±14.7years; 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p<0.001; systemic: IIV3 46.6% vs placebo 39.1%, p<0.001). The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain. Funded by CSL Limited, ClinicalTrials.gov identifier NCT00562484. Copyright © 2016 The Authors. Published by Elsevier

Egg-Independent Influenza Vaccines and Vaccine Candidates

PubMed Central

Manini, Ilaria; Pozzi, Teresa; Rossi, Stefania; Montomoli, Emanuele

2017-01-01

Vaccination remains the principal way to control seasonal infections and is the most effective method of reducing influenza-associated morbidity and mortality. Since the 1940s, the main method of producing influenza vaccines has been an egg-based production process. However, in the event of a pandemic, this method has a significant limitation, as the time lag from strain isolation to final dose formulation and validation is six months. Indeed, production in eggs is a relatively slow process and production yields are both unpredictable and highly variable from strain to strain. In particular, if the next influenza pandemic were to arise from an avian influenza virus, and thus reduce the egg-laying hen population, there would be a shortage of embryonated eggs available for vaccine manufacturing. Although the production of egg-derived vaccines will continue, new technological developments have generated a cell-culture-based influenza vaccine and other more recent platforms, such as synthetic influenza vaccines. PMID:28718786

Protection against Experimental Cryptococcosis following Vaccination with Glucan Particles Containing Cryptococcus Alkaline Extracts.

PubMed

Specht, Charles A; Lee, Chrono K; Huang, Haibin; Tipper, Donald J; Shen, Zu T; Lodge, Jennifer K; Leszyk, John; Ostroff, Gary R; Levitz, Stuart M

2015-12-22

A vaccine capable of protecting at-risk persons against infections due to Cryptococcus neoformans and Cryptococcus gattii could reduce the substantial global burden of human cryptococcosis. Vaccine development has been hampered though, by lack of knowledge as to which antigens are immunoprotective and the need for an effective vaccine delivery system. We made alkaline extracts from mutant cryptococcal strains that lacked capsule or chitosan. The extracts were then packaged into glucan particles (GPs), which are purified Saccharomyces cerevisiae cell walls composed primarily of β-1,3-glucans. Subcutaneous vaccination with the GP-based vaccines provided significant protection against subsequent pulmonary infection with highly virulent strains of C. neoformans and C. gattii. The alkaline extract derived from the acapsular strain was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS), and the most abundant proteins were identified. Separation of the alkaline extract by size exclusion chromatography revealed fractions that conferred protection when loaded in GP-based vaccines. Robust Th1- and Th17-biased CD4(+) T cell recall responses were observed in the lungs of vaccinated and infected mice. Thus, our preclinical studies have indicated promising cryptococcal vaccine candidates in alkaline extracts delivered in GPs. Ongoing studies are directed at identifying the individual components of the extracts that confer protection and thus would be promising candidates for a human vaccine. The encapsulated yeast Cryptococcus neoformans and its closely related sister species, Cryptococcus gattii, are major causes of morbidity and mortality, particularly in immunocompromised persons. This study reports on the preclinical development of vaccines to protect at-risk populations from cryptococcosis. Antigens were extracted from Cryptococcus by treatment with an alkaline solution. The extracted antigens were then packaged into glucan particles, which are hollow

Vaccination with Recombinant Cryptococcus Proteins in Glucan Particles Protects Mice against Cryptococcosis in a Manner Dependent upon Mouse Strain and Cryptococcal Species.

PubMed

Specht, Charles A; Lee, Chrono K; Huang, Haibin; Hester, Maureen M; Liu, Jianhua; Luckie, Bridget A; Torres Santana, Melanie A; Mirza, Zeynep; Khoshkenar, Payam; Abraham, Ambily; Shen, Zu T; Lodge, Jennifer K; Akalin, Ali; Homan, Jane; Ostroff, Gary R; Levitz, Stuart M

2017-11-28

Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs) as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus -derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1) were selected, recombinantly expressed in Escherichia coli , purified, and loaded into GPs. Three mouse strains (C57BL/6, BALB/c, and DR4) were then vaccinated with the antigen-laden GPs, following which they received a pulmonary challenge with virulent C. neoformans and C. gattii strains. Four candidate vaccines (GP-Cda1, GP-Cda2, GP-Cda3, and GP-Sod1) afforded a significant survival advantage in at least one mouse model; some vaccine combinations provided added protection over that seen with either antigen alone. Vaccine-mediated protection against C. neoformans did not necessarily predict protection against C. gattii Vaccinated mice developed pulmonary inflammatory responses that effectively contained the infection; many surviving mice developed sterilizing immunity. Predicted T helper cell epitopes differed between mouse strains and in the degree to which they matched epitopes predicted in humans. Thus, we have discovered cryptococcal proteins that make promising candidate vaccine antigens. Protection varied depending on the mouse strain and cryptococcal species, suggesting that a successful human subunit vaccine will need to contain multiple antigens, including ones that are species specific. IMPORTANCE The encapsulated fungi Cryptococcus neoformans and Cryptococcus gattii are responsible for nearly 200,000 deaths annually, mostly in immunocompromised individuals. An

A small animal peripheral challenge model of yellow fever using interferon-receptor deficient mice and the 17D-204 vaccine strain.

PubMed

Thibodeaux, Brett A; Garbino, Nina C; Liss, Nathan M; Piper, Joseph; Blair, Carol D; Roehrig, John T

2012-05-02

Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne pathogen that requires wild-type (wt), virulent strains to be handled at biosafety level (BSL) 3, with HEPA-filtration of room air exhaust (BSL3+). YFV is found in tropical regions of Africa and South America and causes severe hepatic disease and death in humans. Despite the availability of effective vaccines (17D-204 or 17DD), YFV is still responsible for an estimated 200,000 cases of illness and 30,000 deaths annually. Besides vaccination, there are no other prophylactic or therapeutic strategies approved for use in human YF. Current small animal models of YF require either intra-cranial inoculation of YF vaccine to establish infection, or use of wt strains (e.g., Asibi) in order to achieve pathology. We have developed and characterized a BSL2, adult mouse peripheral challenge model for YFV infection in mice lacking receptors for interferons α, β, and γ (strain AG129). Intraperitoneal challenge of AG129 mice with 17D-204 is a uniformly lethal in a dose-dependent manner, and 17D-204-infected AG129 mice exhibit high viral titers in both brain and liver suggesting this infection is both neurotropic and viscerotropic. Furthermore the use of a mouse model permitted the construction of a 59-biomarker multi-analyte profile (MAP) using samples of brain, liver, and serum taken at multiple time points over the course of infection. This MAP serves as a baseline for evaluating novel therapeutics and their effect on disease progression. Changes (4-fold or greater) in serum and tissue levels of pro- and anti-inflammatory mediators as well as other factors associated with tissue damage were noted in AG129 mice infected with 17D-204 as compared to mock-infected control animals. Published by Elsevier Ltd.

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

PubMed

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

2013-02-18

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 titres (VNTs) in the rat potency model. The increase of VNTs was on average 3-, 15-, 24-fold with adjuvants after one immunization (serotypes 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine compared with two trivalent inactivated influenza vaccines containing alternate B strains in adults: A phase 3, randomized noninferiority study.

PubMed

Treanor, John T; Albano, Frank R; Sawlwin, Daphne C; Graves Jones, Alison; Airey, Jolanta; Formica, Neil; Matassa, Vince; Leong, Jane

2017-04-04

Vaccination is the most effective means of influenza prevention. Efficacy of trivalent vaccines may be enhanced by including both B strain lineages. This phase 3, double-blind study assessed the immunogenicity and safety/tolerability of a quadrivalent inactivated influenza vaccine (IIV4) versus the United States (US)-licensed 2014-2015 trivalent inactivated influenza vaccine (IIV3-Yamagata [IIV3-YAM]; Afluria) and IIV3 containing the alternate Victoria B strain (IIV3-VIC) in adults ≥18years. Participants (n=3484) were randomized 2:1:1 and stratified by age to receive IIV4 (n=1741), IIV3-YAM (n=871), or IIV3-VIC (n=872). The primary objective was to demonstrate noninferiority of the immunological response to IIV4 versus IIV3-YAM and IIV3-VIC. Noninferiority was assessed by hemagglutination inhibition geometric mean titer (GMT) ratio (IIV3/IIV4; upper bound of two-sided 95% confidence interval [CI]≤1.5) and seroconversion rate (SCR) difference (IIV3 - IIV4; upper bound of two-sided 95% CI≤10%) for vaccine strains. Solicited local and systemic adverse events (AEs) were assessed for 7days postvaccination, AEs recorded for 28days postvaccination, and serious AEs for 6months postvaccination. IIV4 elicited a noninferior immune response for matched strains, and superior response for unmatched B strains not contained in IIV3 comparators. Adjusted GMT ratios (95% CI) for A/H1N1, A/H3N2, B/YAM, and B/VIC strains were 0.93 (0.88, 0.99), 0.93 (0.88, 0.98), 0.87 (IIV3-YAM; 0.82, 0.93), and 0.95 (IIV3-VIC; 0.88, 1.03), respectively. Corresponding values for SCR differences (95% CI) were -1.1 (-4.5, 2.3), -1.7 (-5.0, 1.7), -3.2 (IIV3-YAM; -7.4, 0.9), and -1.6 (IIV3-VIC; -5.8, 2.5). AEs were generally mild and experienced by 52.9% of participants. Serious AEs were reported with a slightly higher frequency with IIV4 (2.3%) versus IIV3-YAM (1.6%) and IIV3-VIC (1.5%). IIV4 demonstrated immunological noninferiority to the US-licensed IIV3, and superiority for unmatched B strains

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. Copyright © 2011 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

PubMed Central

Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

2016-01-01

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples.

PubMed

Gautam, Rashi; Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D

2016-01-01

Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8-100% sensitivity, 99.7-100% specificity, 85-95% efficiency and a limit of detection of 4-60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81-92% efficiency and limit of detection of 150-600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98

One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples

PubMed Central

Mijatovic-Rustempasic, Slavica; Esona, Mathew D.; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D.

2016-01-01

Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8–100% sensitivity, 99.7–100% specificity, 85–95% efficiency and a limit of detection of 4–60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81–92% efficiency and limit of detection of 150–600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8�

No demonstrable association between the Leningrad-Zagreb mumps vaccine strain and aseptic meningitis in a large clinical trial in Egypt.

PubMed

Sharma, H J; Oun, S Aly; Bakr, S S Abou; Kapre, S V; Jadhav, S S; Dhere, R M; Bhardwaj, S

2010-04-01

To address the claim that the Leningrad-Zagreb (L-Z) mumps vaccine strain is causally associated with aseptic meningitis, a prospective, post-marketing safety study was conducted with a measles-mumps-rubella vaccine (MMR) (TRESIVAC(R); Serum Institute of India Ltd., Pune, India), which uses the L-Z strain as its mumps component in Egypt. In all, 453 119 children (65 423 children aged 16-24 months and 329 211 children aged 5-7 years) received MMR. The control groups which, as a result of local health regulations, were slightly younger than vaccinees, comprised 12 253 and 46 232 children, respectively. Using questionnaires, the parents recorded solicited local, systemic and neurological adverse events for up to 42 days post-vaccination. All data were analysed externally on an intention-to-treat basis by individuals not participating in the study. Local and/or systemic reactions were reported in a small percentage of participants, with pain, fever and parotitis being the most common signs among vaccinees in both age groups. No case of aseptic meningitis, encephalitis, anaphylaxis or convulsions was observed in any participant. Thus, in this series of more than 450 000 Egyptian children, the L-Z mumps vaccine strain in this vaccine did not cause aseptic meningitis. The vaccine is considerably cheaper than Western competitors and a valid alternative to other MMR vaccines.

Vaccines against meningococcal serogroup B disease containing outer membrane vesicles (OMV)

PubMed Central

Holst, Johan; Oster, Philipp; Arnold, Richard; Tatley, Michael V.; Næss, Lisbeth M.; Aaberge, Ingeborg S.; Galloway, Yvonne; McNicholas, Anne; O’Hallahan, Jane; Rosenqvist, Einar; Black, Steven

2013-01-01

The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004–2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness estimates and communication to the public. The experience with wtOMV vaccines also provide important information for the next generation of MenB vaccines designed to give more comprehensive protection against multiple strains. PMID:23857274

Immunization studies with attenuated strains of Bacillus anthracis.

PubMed Central

Ivins, B E; Ezzell, J W; Jemski, J; Hedlund, K W; Ristroph, J D; Leppla, S H

1986-01-01

Live, attenuated strains of Bacillus anthracis lacking either the capsule plasmid pXO2, the toxin plasmid pXO1, or both were tested for their efficacy as vaccines against intravenous challenge with anthrax toxin in Fischer 344 rats and against aerosol or intramuscular challenge with virulent anthrax spores in Hartley guinea pigs. Animals immunized with toxigenic, nonencapsulated (pXO1+, pXO2-) strains survived toxin and spore challenge and demonstrated postimmunization antibody titers to the three components of anthrax toxin (protective antigen, lethal factor, and edema factor). Immunization with two nontoxigenic, encapsulated (pXO1-, pXO2+), Pasteur vaccine strains neither provided protection nor elicited titers to any of the toxin components. Therefore, to immunize successfully against anthrax toxin or spore challenge, attenuated, live strains of B. anthracis must produce the toxin components specified by the pXO1 plasmid. PMID:3084383

Immunogenicity and efficacy of Hoshino strain of mumps vaccine in Iran; two years study.

PubMed

Avijgan, M; Hafizi, M; Moghni, M; Kheiri, S; Esteghamati, A; Sarikhani, S

2011-06-01

This report describes the immunogenicity and efficacy and long term immunity of Hoshino strain of Mumps (included in MMR Vaccine) in shahr-e-kord, Islamic Republic of Iran (I.R.Iran). A total of 338 Children aged 3-18 years were tested for Mumps IgG using enzyme-linked immunosorbent assay (ELISA). The proportion of susceptible, mumps IgG negative, children was 19.8% (67 subjects). Of the 67 susceptible children, 36 received the MMR vaccination and successfully completed the study. Blood was collected by venipuncture 3, 12, and 24 months after vaccination and serum samples were tested by ELISA for detection of Mumps IgM and IgG. The overall seroconversion rate was 86.1%, 77.7% and 75% at 3, 12, and 24 months after vaccination respectively.

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

2017-03-07

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.

Vaccination against porcine parvovirus protects against disease, but does not prevent infection and virus shedding after challenge infection with a heterologous virus strain.

PubMed

Jóźwik, A; Manteufel, J; Selbitz, H-J; Truyen, U

2009-10-01

The demonstration of field isolates of porcine parvovirus (PPV) that differ genetically and antigenically from vaccine strains of PPV raises the question of whether the broadly used inactivated vaccines can still protect sows against the novel viruses. Ten specific-pathogen-free primiparous sows were assigned to three groups and were vaccinated with one of two vaccines based on the old vaccine strains, or served as non-vaccinated controls. After insemination, all sows were challenged with the prototype genotype 2 virus, PPV-27a, on gestation day 41; fetuses were delivered on gestation day 90 and examined for virus infection. The fetuses of the vaccinated sows were protected against disease, but both the vaccinated and the non-vaccinated sows showed a marked increase in antibody titres after challenge infection, indicating replication of the challenge virus. All sows (vaccinated and non-vaccinated) shed the challenge virus for at least 10 days after infection, with no difference in the pattern or duration of virus shedding.

Proteomic profile of culture filtrate from the Brazilian vaccine strain Mycobacterium bovis BCG Moreau compared to M. bovis BCG Pasteur.

PubMed

Berrêdo-Pinho, Marcia; Kalume, Dario E; Correa, Paloma R; Gomes, Leonardo H F; Pereira, Melissa P; da Silva, Renata F; Castello-Branco, Luiz R R; Degrave, Wim M; Mendonça-Lima, Leila

2011-04-20

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. 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. 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.

Identification of the 1B vaccine strain of Chlamydia abortus in aborted placentas during the investigation of toxaemic and systemic disease in sheep.

PubMed

Sargison, N D; Truyers, I G R; Howie, F E; Thomson, J R; Cox, A L; Livingstone, M; Longbottom, D

2015-09-01

One hundred and forty Cheviot and 100 Suffolk cross Mule primiparous 1-2-year-old ewes, from a flock of about 700 ewes, were vaccinated with an attenuated live 1B strain Chlamydia abortus vaccine about 4 weeks before ram introduction (September 2011). Between 08 March and 01 April 2012, 50 2-year-old ewes aborted and 29 of these died, despite antimicrobial and anti-inflammatory treatment and supportive care. Seven fetuses and three placentae from five 2-year-old ewes were submitted for pathological investigation. The aborted fetuses showed stages of autolysis ranging from being moderately fresh to putrefaction. Unusual, large multifocal regions of thickened membranes, with a dull red granular surface and moderate amounts of grey-white surface exudate were seen on each of the placentae. Intracellular, magenta-staining, acid fast inclusions were identified in Ziehl Neelsen-stained placental smears. Immunohistochemistry for Chlamydia-specific lipopolysaccharide showed extensive positive labelling of the placental epithelia. Molecular analyses of the aborted placentae demonstrated the presence of the 1B vaccine-type strain of C. abortus and absence of any wild-type field strain. The vaccine strain bacterial load of the placental tissue samples was consistent with there being an association between vaccination and abortion. Initial laboratory investigations resulted in a diagnosis of chlamydial abortion. Further investigations led to the identification of the 1B vaccine strain of C. abortus in material from all three of the submitted aborted placentae. Timely knowledge and understanding of any potential problems caused by vaccination against C. abortus are prerequisites for sustainable control of chlamydial abortion. This report describes the investigation of an atypical abortion storm in sheep, and describes the identification of the 1B vaccine strain of C. abortus in products of abortion. The significance of this novel putative association between the vaccine strain

Vaccination with Recombinant Cryptococcus Proteins in Glucan Particles Protects Mice against Cryptococcosis in a Manner Dependent upon Mouse Strain and Cryptococcal Species

PubMed Central

Lee, Chrono K.; Huang, Haibin; Hester, Maureen M.; Liu, Jianhua; Luckie, Bridget A.; Torres Santana, Melanie A.; Mirza, Zeynep; Khoshkenar, Payam; Abraham, Ambily; Shen, Zu T.; Lodge, Jennifer K.; Akalin, Ali; Homan, Jane; Ostroff, Gary R.

2017-01-01

ABSTRACT Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs) as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus-derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii. The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1) were selected, recombinantly expressed in Escherichia coli, purified, and loaded into GPs. Three mouse strains (C57BL/6, BALB/c, and DR4) were then vaccinated with the antigen-laden GPs, following which they received a pulmonary challenge with virulent C. neoformans and C. gattii strains. Four candidate vaccines (GP-Cda1, GP-Cda2, GP-Cda3, and GP-Sod1) afforded a significant survival advantage in at least one mouse model; some vaccine combinations provided added protection over that seen with either antigen alone. Vaccine-mediated protection against C. neoformans did not necessarily predict protection against C. gattii. Vaccinated mice developed pulmonary inflammatory responses that effectively contained the infection; many surviving mice developed sterilizing immunity. Predicted T helper cell epitopes differed between mouse strains and in the degree to which they matched epitopes predicted in humans. Thus, we have discovered cryptococcal proteins that make promising candidate vaccine antigens. Protection varied depending on the mouse strain and cryptococcal species, suggesting that a successful human subunit vaccine will need to contain multiple antigens, including ones that are species specific. PMID:29184017

Impact of age and pre-existing influenza immune responses in humans receiving split inactivated influenza vaccine on the induction of the breadth of antibodies to influenza A strains

PubMed Central

Nuñez, Ivette A.; Carlock, Michael A.; Allen, James D.; Owino, Simon O.; Moehling, Krissy K.; Nowalk, Patricia; Susick, Michael; Diagle, Kensington; Sweeney, Kristen; Mundle, Sophia; Vogel, Thorsten U.; Delagrave, Simon; Ramgopal, Moti; Zimmerman, Richard K.; Kleanthous, Harry

2017-01-01

Most humans have pre-existing immunity to influenza viruses. In this study, volunteers (ages of 18–85 years) were vaccinated with split, inactivated Fluzone™ influenza vaccine in four consecutive influenza seasons from 2013 to 2016 seasons. The impact of repeated vaccination on breadth and durability of antibodies was assessed as a result of vaccine strain changes. Total IgG anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity increased in all age groups against both influenza A HA components in the vaccine post-vaccination (day 21). However, younger subjects maintained seroprotective titers to the vaccine strains, which resulted in higher seroconversion rates in the elderly, since the HAI titers in elderly subjects were more likely to decline prior to the next season. Young subjects had significant HAI activity against historical, as well as contemporary H1 and H3 vaccine strains from the mid-1980s to present. In contrast, elderly subjects had HAI activity to H1 strains from all years, but were more likely to have HAI activity to older strains from 1918-1950s. They also had a more restricted HAI profile against H3 viruses compared to young subjects recognizing H3N2 influenza viruses from the mid-2000s to present. Vaccine recipients were then categorized by whether subjects seroconverted from a seronegative or seropositive pre-vaccination state. Regardless of age, immunological recall or ‘back-boosting’ to antigenically related strains were associated with seroconversion to the vaccine strain. Overall, both younger and older people have the ability to mount a breadth of immune responses following influenza vaccination. This report describes how imprinting exposure differs across age groups, influences antibody cross-reactivity to past hemagglutinin antigenic variants, and shapes immune responses elicited by current split inactivated influenza vaccines. Understanding how current influenza vaccines are influenced by pre

Development of a Novel Vaccine Containing Binary Toxin for the Prevention of Clostridium difficile Disease with Enhanced Efficacy against NAP1 Strains.

PubMed

Secore, Susan; Wang, Su; Doughtry, Julie; Xie, Jinfu; Miezeiewski, Matt; Rustandi, Richard R; Horton, Melanie; Xoconostle, Rachel; Wang, Bei; Lancaster, Catherine; Kristopeit, Adam; Wang, Sheng-Ching; Christanti, Sianny; Vitelli, Salvatore; Gentile, Marie-Pierre; Goerke, Aaron; Skinner, Julie; Strable, Erica; Thiriot, David S; Bodmer, Jean-Luc; Heinrichs, Jon H

2017-01-01

Clostridium difficile infections (CDI) are a leading cause of nosocomial diarrhea in the developed world. The main virulence factors of the bacterium are the large clostridial toxins (LCTs), TcdA and TcdB, which are largely responsible for the symptoms of the disease. Recent outbreaks of CDI have been associated with the emergence of hypervirulent strains, such as NAP1/BI/027, many strains of which also produce a third toxin, binary toxin (CDTa and CDTb). These hypervirulent strains have been associated with increased morbidity and higher mortality. Here we present pre-clinical data describing a novel tetravalent vaccine composed of attenuated forms of TcdA, TcdB and binary toxin components CDTa and CDTb. We demonstrate, using the Syrian golden hamster model of CDI, that the inclusion of binary toxin components CDTa and CDTb significantly improves the efficacy of the vaccine against challenge with NAP1 strains in comparison to vaccines containing only TcdA and TcdB antigens, while providing comparable efficacy against challenge with the prototypic, non-epidemic strain VPI10463. This combination vaccine elicits high neutralizing antibody titers against TcdA, TcdB and binary toxin in both hamsters and rhesus macaques. Finally we present data that binary toxin alone can act as a virulence factor in animal models. Taken together, these data strongly support the inclusion of binary toxin in a vaccine against CDI to provide enhanced protection from epidemic strains of C. difficile.

Development of a Novel Vaccine Containing Binary Toxin for the Prevention of Clostridium difficile Disease with Enhanced Efficacy against NAP1 Strains

PubMed Central

Wang, Su; Doughtry, Julie; Xie, Jinfu; Miezeiewski, Matt; Rustandi, Richard R.; Horton, Melanie; Xoconostle, Rachel; Wang, Bei; Lancaster, Catherine; Kristopeit, Adam; Wang, Sheng-Ching; Christanti, Sianny; Vitelli, Salvatore; Gentile, Marie-Pierre; Goerke, Aaron; Skinner, Julie; Strable, Erica; Thiriot, David S.; Bodmer, Jean-Luc; Heinrichs, Jon H.

2017-01-01

Clostridium difficile infections (CDI) are a leading cause of nosocomial diarrhea in the developed world. The main virulence factors of the bacterium are the large clostridial toxins (LCTs), TcdA and TcdB, which are largely responsible for the symptoms of the disease. Recent outbreaks of CDI have been associated with the emergence of hypervirulent strains, such as NAP1/BI/027, many strains of which also produce a third toxin, binary toxin (CDTa and CDTb). These hypervirulent strains have been associated with increased morbidity and higher mortality. Here we present pre-clinical data describing a novel tetravalent vaccine composed of attenuated forms of TcdA, TcdB and binary toxin components CDTa and CDTb. We demonstrate, using the Syrian golden hamster model of CDI, that the inclusion of binary toxin components CDTa and CDTb significantly improves the efficacy of the vaccine against challenge with NAP1 strains in comparison to vaccines containing only TcdA and TcdB antigens, while providing comparable efficacy against challenge with the prototypic, non-epidemic strain VPI10463. This combination vaccine elicits high neutralizing antibody titers against TcdA, TcdB and binary toxin in both hamsters and rhesus macaques. Finally we present data that binary toxin alone can act as a virulence factor in animal models. Taken together, these data strongly support the inclusion of binary toxin in a vaccine against CDI to provide enhanced protection from epidemic strains of C. difficile. PMID:28125650

In-depth genome analyses of viruses from vaccine-derived rabies cases and corresponding live-attenuated oral rabies vaccines.

PubMed

Pfaff, Florian; Müller, Thomas; Freuling, Conrad M; Fehlner-Gardiner, Christine; Nadin-Davis, Susan; Robardet, Emmanuelle; Cliquet, Florence; Vuta, Vlad; Hostnik, Peter; Mettenleiter, Thomas C; Beer, Martin; Höper, Dirk

2018-02-10

Live-attenuated rabies virus strains such as those derived from the field isolate Street Alabama Dufferin (SAD) have been used extensively and very effectively as oral rabies vaccines for the control of fox rabies in both Europe and Canada. Although these vaccines are safe, some cases of vaccine-derived rabies have been detected during rabies surveillance accompanying these campaigns. In recent analysis it was shown that some commercial SAD vaccines consist of diverse viral populations, rather than clonal genotypes. For cases of vaccine-derived rabies, only consensus sequence data have been available to date and information concerning their population diversity was thus lacking. In our study, we used high-throughput sequencing to analyze 11 cases of vaccine-derived rabies, and compared their viral population diversity to the related oral rabies vaccines using pairwise Manhattan distances. This extensive deep sequencing analysis of vaccine-derived rabies cases observed during oral vaccination programs provided deeper insights into the effect of accidental in vivo replication of genetically diverse vaccine strains in the central nervous system of target and non-target species under field conditions. The viral population in vaccine-derived cases appeared to be clonal in contrast to their parental vaccines. The change from a state of high population diversity present in the vaccine batches to a clonal genotype in the affected animal may indicate the presence of a strong bottleneck during infection. In conclusion, it is very likely that these few cases are the consequence of host factors and not the result of the selection of a more virulent genotype. Furthermore, this type of vaccine-derived rabies leads to the selection of clonal genotypes and the selected variants were genetically very similar to potent SAD vaccines that have undergone a history of in vitro selection. Copyright © 2018. Published by Elsevier Ltd.

Antigenic characterization of a formalin-inactivated poliovirus vaccine derived from live-attenuated Sabin strains.

PubMed

Tano, Yoshio; Shimizu, Hiroyuki; Martin, Javier; Nishimura, Yorihiro; Simizu, Bunsiti; Miyamura, Tatsuo

2007-10-10

A candidate inactivated poliovirus vaccine derived from live-attenuated Sabin strains (sIPV), which are used in the oral poliovirus vaccine (OPV), was prepared in a large-production scale. The modification of viral antigenic epitopes during the formalin inactivation process was investigated by capture ELISA assays using type-specific and antigenic site-specific monoclonal antibodies (MoAbs). The major antigenic site 1 was modified during the formalin inactivation of Sabin 1. Antigenic sites 1-3 were slightly modified during the formalin inactivation of Sabin 2 strain. Sites 1 and 3 were altered on inactivated Sabin 3 virus. These alterations were different to those shown by wild-type Saukett strain, used in conventional IPV (cIPV). It has been previously reported that type 1 sIPV showed higher immunogenicity to type 1 cIPV whereas types 2 and 3 sIPV induced lower level of immunogenicity than their cIPV counterparts. Our results suggest that the differences in epitope structure after formalin inactivation may account, at least in part, for the observed differences in immunogenicity between Sabin and wild-type inactivated poliovaccines.

Is there a lack of information on HPV vaccination given by health professionals to young women?

PubMed

La Torre, G; De Vito, E; Ficarra, M G; Firenze, A; Gregorio, P; Boccia, A

2013-10-01

The aim of this survey is to compare the main sources of information about vaccination against Human papillomavirus (HPV) of young women aged over-18 and under-18 years. A multicenter study was carried out in Italy through the administration of a questionnaire. Univariate analyses were conducted to evaluate possible differences between age groups and different locations (chi-square test and Fisher test where possible). The sample consisted of 987 young women. The main sources of information about HPV vaccination are represented by magazines/books (23.1%) and TV (20.5%) for the over-18s, while for the under-18s the sources are general practitioners (22.6%) and pediatricians (15.4%). The over-18s with health professionals as parents consult mostly gynecologists (27.7%) and general practitioners (20.5%). This study highlights lack of information on HPV vaccination given by health professionals to young women and underlines the need to improve education about cervical cancer, prevention and HPV vaccination. Copyright © 2013 Elsevier Ltd. All rights reserved.

Real-time reverse transcription polymerase chain reaction method for detection of Canine distemper virus modified live vaccine shedding for differentiation from infection with wild-type strains.

PubMed

Wilkes, Rebecca P; Sanchez, Elena; Riley, Matthew C; Kennedy, Melissa A

2014-01-01

Canine distemper virus (CDV) remains a common cause of infectious disease in dogs, particularly in high-density housing situations such as shelters. Vaccination of all dogs against CDV is recommended at the time of admission to animal shelters and many use a modified live virus (MLV) vaccine. From a diagnostic standpoint for dogs with suspected CDV infection, this is problematic because highly sensitive diagnostic real-time reverse transcription polymerase chain reaction (RT-PCR) tests are able to detect MLV virus in clinical samples. Real-time PCR can be used to quantitate amount of virus shedding and can differentiate vaccine strains from wild-type strains when shedding is high. However, differentiation by quantitation is not possible in vaccinated animals during acute infection, when shedding is low and could be mistaken for low level vaccine virus shedding. While there are gel-based RT-PCR assays for differentiation of vaccine strains from field strains based on sequence differences, the sensitivity of these assays is unable to match that of the real-time RT-PCR assay currently used in the authors' laboratory. Therefore, a real-time RT-PCR assay was developed that detects CDV MLV vaccine strains and distinguishes them from wild-type strains based on nucleotide sequence differences, rather than the amount of viral RNA in the sample. The test is highly sensitive, with detection of as few as 5 virus genomic copies (corresponding to 10(-1) TCID(50)). Sequencing of the DNA real-time products also allows phylogenetic differentiation of the wild-type strains. This test will aid diagnosis during outbreaks of CDV in recently vaccinated animals.

Cloning and expression of Clostridium perfringens type D vaccine strain epsilon toxin gene in E. coli as a recombinant vaccine candidate.

PubMed

Aziminia, Parastoo; Pilehchian-Langroudi, Reza; Esmaeilnia, Kasra

2016-08-01

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. 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. 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. 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.

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

Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies.

PubMed

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; Montefiori, David C

2014-03-01

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. 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. Efforts to elicit

Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi

PubMed Central

Nakagomi, Toyoko; Nakagomi, Osamu; Dove, Winifred; Doan, Yen Hai; Witte, Desiree; Ngwira, Bagrey; Todd, Stacy; Steele, A Duncan; Neuzil, Kathleen M; Cunliffe, Nigel A

2014-01-01

The human, G1P[8] rotavirus vaccine (Rotarix) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P[8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains. PMID:22520123

Impact of antigens, adjuvants and strains on sexually dimorphic antibody response to vaccines in mice.

PubMed

Li, Xin; Guo, Sheng; Yang, Lei; Hua, Li; Li, Zhiqin; Hao, Xu; Yu, Yongli; Sun, Wei; Wang, Liying

2017-07-01

Sexually dimorphic antibody response to vaccines has long been noticed. In addition to sex hormones, other factors such as antigens, adjuvants and strains of mice, as shown by indirect evidence, could also impact the sexual dimorphism. To clarify this, we immunized both gender mice of distinct strains with inactivated FMDV or HBsAg with or without adjuvants, and detected the specific antibody response of the mice. We found that in absence of adjuvants, the recombinant HBsAg but not the inactivated FMDV induced enhanced IgG antibody response in the female BALB/c mice. The o/w emulsion could facilitate the HBsAg to induce the comparable level of IgG antibodies in the male BALB/c mice as that in the females. The o/w emulsion rather than ISA206, a w/o/w emulsion, could assist the inactivated FMDV to induce higher levels of IgM antibodies in the female BALB/c mice. Moreover, the sexually dimorphic antibody response varied among the ICR, BALB/c and the F1 (BALB/c × C57BL/6) mice. Thus the data suggest that antigens, adjuvants and strains all impact the sexually dimorphic antibody response to vaccines and may provide insights for developing gender-based vaccines. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Evaluation of two strains of Marek's disease virus serotype 1 for the development of recombinant vaccines against very virulent infectious bursal disease virus.

PubMed

Li, Kai; Liu, Yongzhen; Liu, Changjun; Gao, Li; Gao, Yulong; Zhang, Yanping; Cui, Hongyu; Qi, Xiaole; Zhong, Li; Wang, Xiaomei

2017-03-01

Attenuated strains of Marek's disease virus serotype 1 (MDV1), and the closely related herpesvirus of turkeys, are among the most potent vectors for development of recombinant vaccines for poultry. To investigate the effects of MDV1 strain characteristics on the protective efficacy of the recombinant vaccines, we developed two recombinant MDV1 vaccines for expressing the VP2 gene of infectious bursal disease virus (IBDV) based on two different MDV1 strains, the attenuated strain 814 and the Meq gene-deleted recombinant MDV1 strain rLMS△Meq, as the viral vectors. The r814-VP2 virus based on the 814 strain exhibited higher replication efficiency in cell culture while lower viral titers in chickens, compared to rLMS△Meq-VP2 derived from the rLMS△Meq strain. Further studies indicated that r814-VP2 produced higher levels of VP2 protein in cells and elicited stronger immune responses against IBDV in chickens than rLMS△Meq-VP2. After IBDV challenge, rLMS△Meq-VP2 provided 50% protection against mortality, and the birds that survived developed bursal atrophy and gross lesions. In contrast, r814-VP2 conferred complete protection not only against development of clinical signs and mortality, but also against the formation of bursal lesions. The results indicate that different MDV1 vector influences the protective efficacy of recombinant MDV1 vaccines. The r814-VP2 has the potential to serve as a bivalent vaccine against two important lethal pathogens of chickens. Copyright © 2016 Elsevier B.V. All rights reserved.

Simultaneous co-detection of wild-type and vaccine strain measles virus using the BD MAX system.

PubMed

Thapa, Kiran; Ellem, Justin A; Basile, Kerri; Carter, Ian; Olma, Tom; Chen, Sharon C-A; Dwyer, Dominic E; Kok, Jen

2018-06-01

Despite the reported elimination of measles virus in Australia, importation of cases from endemic countries continues to lead to secondary local transmission and outbreaks. Rapid laboratory confirmation of measles is paramount for individual patient management and outbreak responses. Further, it is important to rapidly distinguish infection from wild-type virus or vaccine strains to guide public health responses. We developed a high throughput, TaqMan-based multiplex reverse-transcription-polymerase chain reaction (PCR) assay using the BD MAX platform (Becton Dickinson) that simultaneously detects measles virus and differentiates between wild-type and vaccine strains without the need for sequencing. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR

PubMed Central

Nishiyama, Shoko; Slack, Olga A. L.; Lokugamage, Nandadeva; Hill, Terence E.; Juelich, Terry L.; Zhang, Lihong; Smith, Jennifer K.; Perez, David; Gong, Bin; Freiberg, Alexander N.; Ikegami, Tetsuro

2016-01-01

ABSTRACT Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRΔE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRΔE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRΔE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker. PMID:27248570

Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR.

PubMed

Nishiyama, Shoko; Slack, Olga A L; Lokugamage, Nandadeva; Hill, Terence E; Juelich, Terry L; Zhang, Lihong; Smith, Jennifer K; Perez, David; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

2016-11-16

Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRΔE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRΔE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRΔE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker.

Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA- (High Temperature Requirement A) Sterne Strain

PubMed Central

Chitlaru, Theodor; Israeli, Ma’ayan; Bar-Haim, Erez; Elia, Uri; Rotem, Shahar; Ehrlich, Sharon; Cohen, Ofer; Shafferman, Avigdor

2016-01-01

Anthrax is a lethal disease caused by the gram-positive spore-producing bacterium Bacillus anthracis. Live attenuated vaccines, such as the nonencapsulated Sterne strain, do not meet the safety standards mandated for human use in the Western world and are approved for veterinary purposes only. Here we demonstrate that disrupting the htrA gene, encoding the chaperone/protease HtrA (High Temperature Requirement A), in the virulent Bacillus anthracis Vollum strain results in significant virulence attenuation in guinea pigs, rabbits and mice, underlying the universality of the attenuated phenotype associated with htrA knockout. Accordingly, htrA disruption was implemented for the development of a Sterne-derived safe live vaccine compatible with human use. The novel B. anthracis SterneΔhtrA strain secretes functional anthrax toxins but is 10–104-fold less virulent than the Sterne vaccine strain depending on animal model (mice, guinea pigs, or rabbits). In spite of this attenuation, double or even single immunization with SterneΔhtrA spores elicits immune responses which target toxaemia and bacteremia resulting in protection from subcutaneous or respiratory lethal challenge with a virulent strain in guinea pigs and rabbits. The efficacy of the immune-protective response in guinea pigs was maintained for at least 50 weeks after a single immunization. PMID:26732659

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of a chimeric Plasmodium berghei strain expressing the repeat region of the P. vivax circumsporozoite protein for in vivo evaluation of vaccine efficacy.

PubMed

Espinosa, Diego A; Yadava, Anjali; Angov, Evelina; Maurizio, Paul L; Ockenhouse, Christian F; Zavala, Fidel

2013-08-01

The development of vaccine candidates against Plasmodium vivax-the most geographically widespread human malaria species-is challenged by technical difficulties, such as the lack of in vitro culture systems and availability of animal models. Chimeric rodent Plasmodium parasites are safe and useful tools for the preclinical evaluation of new vaccine formulations. We report the successful development and characterization of chimeric Plasmodium berghei parasites bearing the type I repeat region of P. vivax circumsporozoite protein (CSP). The P. berghei-P. vivax chimeric strain develops normally in mosquitoes and produces highly infectious sporozoites that produce patent infection in mice that are exposed to the bites of as few as 3 P. berghei-P. vivax-infected mosquitoes. Using this transgenic parasite, we demonstrate that monoclonal and polyclonal antibodies against P. vivax CSP strongly inhibit parasite infection and thus support the notion that these antibodies play an important role in protective immunity. The chimeric parasites we developed represent a robust model for evaluating protective immune responses against P. vivax vaccines based on CSP.

Genomic Sequence and Virulence of Clonal Isolates of Vaccinia Virus Tiantan, the Chinese Smallpox Vaccine Strain

PubMed Central

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. PMID:23593246

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.

Sequence analysis of VP7 and VP4 genes of G1P[8] rotaviruses circulating among diarrhoeic children in Pune, India: a comparison with Rotarix and RotaTeq vaccine strains.

PubMed

Kulkarni, Ruta; Arora, Ritu; Arora, Rashmi; Chitambar, Shobha D

2014-08-11

The G1P[8] rotaviruses are a common cause of rotavirus diarrhoea among children in India. Two rotavirus vaccines licensed in India, Rotarix and RotaTeq, contain strains with G1 and P[8] genotypes. A comparative analysis of these genotypes in the live rotavirus vaccines with circulating rotavirus strains is essential for assessment of rotavirus diversity. G1P[8] strains detected during rotavirus surveillance among diarrhoeic children hospitalized in Pune in 1992-1993 and 2006-2008, were included in the study. Amplification, sequencing and phylogenetic analysis of the VP7 and VP4 genes were carried out for identification of the G1 and P[8] lineages, respectively. Antigenic epitopes of VP7 and VP4 encoded proteins were compared to determine the differences between the G1P[8] strains from Pune and the vaccine strains. G1-Lineage 1, P[8]-Lineage 3 strains were predominant in Pune during 1992-1993 and 2006-2008. Strains of G1-Lineage 2, P[8]-Lineage 3 and G1-Lineage 1, P[8]-Lineage 4 were detected at low levels during 2006-2008. The G1-Lineage 1, P[8]-Lineage 3 strains showed up to eight amino acid changes, each in the VP7 and VP4 epitopes, with respect to the Rotarix vaccine strain (G1-Lineage 2, P[8]-Lineage 1) and the G1 (Lineage-3) and P[8] (Lineage 2) components of the RotaTeq vaccine. The G1-Lineage 2 strains were closer to both vaccine strains with no or only two amino acid substitutions in the VP7 epitopes. The divergent P[8]-Lineage 4 (OP354-like) strains showed fourteen and fifteen amino acid differences, with Rotarix and RotaTeq vaccine strains, respectively, in the VP4 epitopes. The differences between the G1P[8] strains in Pune and the G1 and P[8] components of the vaccine strains need to be described for appropriate evaluation of vaccine shedding. Continuous monitoring of the G1P[8] subgenotypic lineages would be necessary to study any long term impact of vaccine use on G1P[8] strain evolution. Copyright © 2014. Published by Elsevier Ltd.

Measles Vaccine Strain Genotype A from the Skin Rash of a DiGeorge Patient on a TNF Inhibitor

PubMed Central

Tam, Pui-Ying Iroh; Hanisch, Benjamin R.; Klammer, Kate; DeVries, Aaron S.

2015-01-01

Isolation of measles virus is typically from respiratory, blood or urine specimens. We describe the first known case of measles vaccine-associated disease in a patient on TNF inhibitor therapy in which genotype A Edmonston vaccine strain virus was identified from skin scrapings of the patient’s rash. PMID:24346604

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

Identification of a new genetic marker in Mycoplasma synoviae vaccine strain MS-H and development of a strategy using polymerase chain reaction and high-resolution melting curve analysis for differentiating MS-H from field strains.

PubMed

Zhu, Ling; Konsak, Barbara M; Olaogun, Olusola M; Agnew-Crumptona, Rebecca; Kanci, Anna; Marenda, Marc S; Browning, Glenn F; Noormohammadi, Amir H

2017-10-01

Mycoplasma synoviae (MS) is an economically important avian pathogen worldwide, causing subclinical respiratory tract infection and infectious synovitis in chickens and turkeys. A temperature-sensitive (ts + ) live attenuated vaccine MS-H, derived from the Australian field strain 86079/7NS, is now widely used in many countries to control the disease induced by MS. Differentiation of MS-H vaccine from field strains is crucial for monitoring vaccination programs in commercial poultry. Comparison of genomic sequences of MS-H and its parent strain revealed an adenine deletion at nucleotide position 468 of the MS-H oppF-1 gene. This mutation was shown to be unique to MS-H in further comparative analyses of oppF-1 genes of MS-H re-isolates and field strains from Australia and other countries. Based on this single nucleotide, a combination of nested PCR and high-resolution melting (HRM) curve analysis was used to evaluate its potential for use in differentiation of MS-H from field strains. The mean genotype confidence percentages of 99.27 and 48.20 for MS-H and field strains, respectively, demonstrated the high discriminative power of the newly developed assay (oppF PCR-HRM). A set of 13 tracheal swab samples collected from MS-H vaccinated specific pathogen free birds and commercial chicken flocks infected with MS were tested using the oppF PCR-HRM test and results were totally consistent with those obtained using vlhA genotyping. The nested-PCR HRM method established in this study proved to be a rapid, simple and cost effective tool for discriminating the MS-H vaccine strain from Australian and international strains in pure cultures and on tracheal swabs. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi.

PubMed

Nakagomi, Toyoko; Nakagomi, Osamu; Dove, Winifred; Doan, Yen Hai; Witte, Desiree; Ngwira, Bagrey; Todd, Stacy; Duncan Steele, A; Neuzil, Kathleen M; Cunliffe, Nigel A

2012-04-27

The human, G1P[8] rotavirus vaccine (Rotarix™) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix™) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P[8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or the DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains. Copyright © 2011 Elsevier Ltd. All rights reserved.

A novel live attenuated anthrax spore vaccine based on an acapsular Bacillus anthracis Sterne strain with mutations in the htrA, lef and cya genes.

PubMed

Chitlaru, Theodor; Israeli, Ma'ayan; Rotem, Shahar; Elia, Uri; Bar-Haim, Erez; Ehrlich, Sharon; Cohen, Ofer; Shafferman, Avigdor

2017-10-20

We recently reported the development of a novel, next-generation, live attenuated anthrax spore vaccine based on disruption of the htrA (High Temperature Requirement A) gene in the Bacillus anthracis Sterne veterinary vaccine strain. This vaccine exhibited a highly significant decrease in virulence in murine, guinea pig and rabbit animal models yet preserved the protective value of the parental Sterne strain. Here, we report the evaluation of additional mutations in the lef and cya genes, encoding for the toxin components lethal factor (LF) and edema factor (EF), to further attenuate the SterneΔhtrA strain and improve its compatibility for human use. Accordingly, we constructed seven B. anthracis Sterne-derived strains exhibiting different combinations of mutations in the htrA, cya and lef genes. The various strains were indistinguishable in growth in vitro and in their ability to synthesise the protective antigen (PA, necessary for the elicitation of protection). In the sensitive murine model, we observed a gradual increase (ΔhtrA<ΔhtrAΔcya<ΔhtrAΔlef<ΔhtrAΔlefΔcya) in attenuation - up to 10 8 -fold relative to the parental Sterne vaccine strain. Most importantly, all various SterneΔhtrA derivative strains did not differ in their ability to elicit protective immunity in guinea pigs. Immunisation of guinea pigs with a single dose (10 9 spores) or double doses (>10 7 spores) of the most attenuated triple mutant strain SterneΔhtrAlef MUT Δcya induced a robust immune response, providing complete protection against a subsequent respiratory lethal challenge. Partial protection was observed in animals vaccinated with a double dose of as few as 10 5 spores. Furthermore, protective immune status was maintained in all vaccinated guinea pigs and rabbits for at least 40 and 30weeks, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development

PubMed Central

Rella, Antonella; Mor, Visesato; Farnoud, Amir M.; Singh, Ashutosh; Shamseddine, Achraf A.; Ivanova, Elitza; Carpino, Nicholas; Montagna, Maria T.; Luberto, Chiara; Del Poeta, Maurizio

2015-01-01

Cryptococcosis caused by Cryptococcus neoformans and Cryptococcus gattii affects a large population and is a cause of significant morbidity and mortality. Despite its public health burden, there are currently no vaccines against cryptococcosis and new strategies against such infections are needed. In this study, we demonstrate that C. neoformans has the biochemical ability to metabolize sterylglucosides (SGs), a class of immunomodulatory glycolipids. Genetic manipulations that eliminate cryptococccal sterylglucosidase lead to the accumulation of SGs and generate a mutant strain (Δsgl1) that is non-pathogenic in the mouse models of cryptococcosis. Interestingly, this mutant strain acts as a vaccine strain and protects mice against cryptococcosis following infection with C. neoformans or C. gattii. The immunity induced by the Δsgl1 strain is not CD4+ T-cells dependent. Immunocompromised mice, which lack CD4+ T-cells, are able to control the infection by Δsgl1 and acquire immunity against the challenge by wild-type C. neoformans following vaccination with the Δsgl1 strain. These findings are particularly important in the context of HIV/AIDS immune deficiency and suggest that the Δsgl1 strain might provide a potential vaccination strategy against cryptococcosis. PMID:26322039

Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development.

PubMed

Rella, Antonella; Mor, Visesato; Farnoud, Amir M; Singh, Ashutosh; Shamseddine, Achraf A; Ivanova, Elitza; Carpino, Nicholas; Montagna, Maria T; Luberto, Chiara; Del Poeta, Maurizio

2015-01-01

Cryptococcosis caused by Cryptococcus neoformans and Cryptococcus gattii affects a large population and is a cause of significant morbidity and mortality. Despite its public health burden, there are currently no vaccines against cryptococcosis and new strategies against such infections are needed. In this study, we demonstrate that C. neoformans has the biochemical ability to metabolize sterylglucosides (SGs), a class of immunomodulatory glycolipids. Genetic manipulations that eliminate cryptococccal sterylglucosidase lead to the accumulation of SGs and generate a mutant strain (Δsgl1) that is non-pathogenic in the mouse models of cryptococcosis. Interestingly, this mutant strain acts as a vaccine strain and protects mice against cryptococcosis following infection with C. neoformans or C. gattii. The immunity induced by the Δsgl1 strain is not CD4(+) T-cells dependent. Immunocompromised mice, which lack CD4(+) T-cells, are able to control the infection by Δsgl1 and acquire immunity against the challenge by wild-type C. neoformans following vaccination with the Δsgl1 strain. These findings are particularly important in the context of HIV/AIDS immune deficiency and suggest that the Δsgl1 strain might provide a potential vaccination strategy against cryptococcosis.

Rational development of an attenuated recombinant cyprinid herpesvirus 3 vaccine using prokaryotic mutagenesis and in vivo bioluminescent imaging.

PubMed

Boutier, Maxime; Ronsmans, Maygane; Ouyang, Ping; Fournier, Guillaume; Reschner, Anca; Rakus, Krzysztof; Wilkie, Gavin S; Farnir, Frédéric; Bayrou, Calixte; Lieffrig, François; Li, Hong; Desmecht, Daniel; Davison, Andrew J; Vanderplasschen, Alain

2015-02-01

Cyprinid herpesvirus 3 (CyHV 3) is causing severe economic losses worldwide in common and koi carp industries, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We produced single deleted recombinants using prokaryotic mutagenesis. When producing a recombinant lacking open reading frame 134 (ORF134), we unexpectedly obtained a clone with additional deletion of ORF56 and ORF57. This triple deleted recombinant replicated efficiently in vitro and expressed an in vivo safety/efficacy profile compatible with use as an attenuated vaccine. To determine the role of the double ORF56-57 deletion in the phenotype and to improve further the quality of the vaccine candidate, a series of deleted recombinants was produced and tested in vivo. These experiments led to the selection of a double deleted recombinant lacking ORF56 and ORF57 as a vaccine candidate. The safety and efficacy of this strain were studied using an in vivo bioluminescent imaging system (IVIS), qPCR, and histopathological examination, which demonstrated that it enters fish via skin infection similar to the wild type strain. However, compared to the parental wild type strain, the vaccine candidate replicated at lower levels and spread less efficiently to secondary sites of infection. Transmission experiments allowing water contamination with or without additional physical contact between fish demonstrated that the vaccine candidate has a reduced ability to spread from vaccinated fish to naïve sentinel cohabitants. Finally, IVIS analyses demonstrated that the vaccine candidate induces a protective mucosal immune response at the portal of entry. Thus, the present study is the first to report the rational development of a recombinant attenuated vaccine against CyHV 3 for mass vaccination of carp. We also demonstrated the relevance of the CyHV 3 carp model for studying alloherpesvirus transmission and mucosal immunity in teleost skin.

Vaccination with Brucella abortus rough mutant RB51 protects BALB/c mice against virulent strains of Brucella abortus, Brucella melitensis, and Brucella ovis.

PubMed Central

Jiménez de Bagüés, M P; Elzer, P H; Jones, S M; Blasco, J M; Enright, F M; Schurig, G G; Winter, A J

1994-01-01

Vaccination of BALB/c mice with live Brucella abortus RB51, a stable rough mutant, produced protection against challenge with virulent strains of Brucella abortus, Brucella melitensis, and Brucella ovis. Passive-transfer experiments indicated that vaccinated mice were protected against B. abortus 2308 through cell-mediated immunity, against B. ovis PA through humoral immunity, and against B. melitensis 16M through both forms of immunity. Live bacteria were required for the induction of protective cell-mediated immunity; vaccination with whole killed cells of strain RB51 failed to protect mice against B. abortus 2308 despite development of good delayed-type hypersensitivity reactions. Protective antibodies against the heterologous species were generated in vaccinated mice primarily through anamnestic responses following challenge infections. Growth of the antigenically unrelated bacterium Listeria monocytogenes in the spleens of vaccinated mice indicated that nonspecific killing by residual activated macrophages contributed minimally to protection. These results encourage the continued investigation of strain RB51 as an alternative vaccine against heterologous Brucella species. However, its usefulness against B. ovis would be limited if, as suggested here, epitopes critical for protective cell-mediated immunity are not shared between B. abortus and B. ovis. Images PMID:7927779

The effect of vaccination with the PAV-250 strain classical swine fever (CSF) virus on the airborne transmission of CSF virus.

PubMed

Gonzalez, C; Pijoan, C; Ciprian, A; Correa, P; Mendoza, S

2001-09-01

The airborne transmission of Classical Swine Fever (CSF) virus to susceptible pigs, as well as the effect of vaccination with the CSF virus PAV-250 strain was investigated on this mode of transmission. Experiment I: four pigs were inoculated with the ALD CSFV strain (10(4.3) 50% TCID) by the intramuscular route, and at the onset of fever, they were introduced into an enclosed chamber. At the end of the experiment surviving pigs were sedated, anesthetized and euthanatized. Experiment II: four pigs were previously vaccinated with the CSF virus PAV-250 strain, and at 14 days post-vaccination they were challenged with the CSF virus ALD strain. In both experiments, four susceptible pigs were exposed to infectious aerosols by placing them in a chamber connected by a duct to the adjacent pen containing the infected animals and were kept there for 86 hs. In Experiment I, pigs exposed to contaminated air died as a result of infection with CSF virus on days 14, 21 and 28 post-inhalation. These four pigs seroconverted from day 12 post-inhalation. CSF virus was isolated from these animals, and the fluorescent antibody test on tonsils was positive. In Experiment II, a vaccinated pig exposed to contaminated air did not seroconvert, nor was CSF virus isolated from lymphoid tissues. However, mild fluorescence in tonsil sections from these pigs was observed. In conclusion, CSF virus was shown to be transmitted by air at a distance of 1 m to susceptible pigs. Vaccination with the PAV-250 CSF virus strain protected the pigs from clinical disease under the same conditions.

A comparative study of multiple clinical enterovirus 71 isolates and evaluation of cross protection of inactivated vaccine strain FY-23 K-B in vitro.

PubMed

Yang, Ting; Li, Hua; Yue, Lei; Song, Xia; Xie, Tianhong; Ma, Shaohui; Meng, Huaqing; Zhang, Ye; He, Xin; Long, Runxiang; Yang, Rong; Luo, Fangyu; Xie, Zhongping; Li, Qihan

2017-10-26

Enterovirus 71 (EV71) is one of the causative agents of hand, foot and mouth disease, which mostly affects infants and children and leads to severe neurological diseases. Vaccination offers the best option for disease control. We have screened the virus strain FY-23 K-B, which is used as an inactivated vaccine strain. An important issue in the development of vaccines is whether they provide cross protection against all other strains. We collected and identified 19 clinical EV71 isolates from mainland China, which all belong to the C4 genotype. We established growth curves of the strains in Vero cells, performed genetic analysis, and evaluated the cross protection efficacy through neutralizing assays using antisera from a rabbit, monkey and adult human immunized with the FY-23 K-B vaccine strain. The antisera showed broad cross protection among the C4 subgroup strains and homotype strain. Neutralizing indexes (NIs) among the isolates and homotype strain of antisera varied between 56.2-1995.3 for rabbit, 17.8-42,169.7 for monkey and 31.6-17,782.8 for human, whereas NIs against Coxsackievirus A16 or other enteroviruses were below 10. These results suggested that FY-23 K-B used as an antigen could elicit broad spectrum neutralizing antibodies with cross protective efficacy among C4 genotype strains.

Preparation for emergence of an Eastern European porcine reproductive and respiratory syndrome virus (PRRSV) strain in Western Europe: Immunization with modified live virus vaccines or a field strain confers partial protection.

PubMed

Renson, P; Fablet, C; Le Dimna, M; Mahé, S; Touzain, F; Blanchard, Y; Paboeuf, F; Rose, N; Bourry, O

2017-05-01

The porcine reproductive and respiratory syndrome virus (PRRSV) causes huge economic losses for the swine industry worldwide. In the past several years, highly pathogenic strains that lead to even greater losses have emerged. For the Western European swine industry, one threat is the possible introduction of Eastern European PRRSV strains (example Lena genotype 1.3) which were shown to be more virulent than common Western resident strains under experimental conditions. To prepare for the possible emergence of this strain in Western Europe, we immunized piglets with a Western European PRRSV field strain (Finistere: Fini, genotype 1.1), a new genotype 1 commercial modified live virus (MLV) vaccine (MLV1) or a genotype 2 commercial MLV vaccine (MLV2) to evaluate and compare the level of protection that these strains conferred upon challenge with the Lena strain 4 weeks later. Results show that immunization with Fini, MLV1 or MLV2 strains shortened the Lena-induced hyperthermia. In the Fini group, a positive effect was also demonstrated in growth performance. The level of Lena viremia was reduced for all immunized groups (significantly so for Fini and MLV2). This reduction in Lena viremia was correlated with the level of Lena-specific IFNγ-secreting cells. In conclusion, we showed that a commercial MLV vaccine of genotype 1 or 2, as well as a field strain of genotype 1.1 may provide partial clinical and virological protection upon challenge with the Lena strain. The cross-protection induced by these immunizing strains was not related with the level of genetic similarity to the Lena strain. The slightly higher level of protection established with the field strain is attributed to a better cell-mediated immune response. Copyright © 2017 Elsevier B.V. All rights reserved.

Avirulent Marek’s Disease Virus Type 1 Strain 814 Vectored Vaccine Expressing Avian Influenza (AI) Virus H5 Haemagglutinin Induced Better Protection Than Turkey Herpesvirus Vectored AI Vaccine

PubMed Central

Cui, Xianlan; Zhao, Yan; Shi, Xingming; Li, Qiaoling; Yan, Shuai; Gao, Ming; Wang, Mei; Liu, Changjun; Wang, Yunfeng

2013-01-01

Background Herpesvirus of turkey (HVT) as a vector to express the haemagglutinin (HA) of avian influenza virus (AIV) H5 was developed and its protection against lethal Marek’s disease virus (MDV) and highly pathogenic AIV (HPAIV) challenges was evaluated previously. It is well-known that avirulemt MDV type 1 vaccines are more effective than HVT in prevention of lethal MDV infection. To further increase protective efficacy against HPAIV and lethal MDV, a recombinant MDV type 1 strain 814 was developed to express HA gene of HPAIV H5N1. Methodology/Principal Findings A recombinant MDV-1 strain 814 expressing HA gene of HPAIV H5N1 virus A/goose/Guangdong/3/96 at the US2 site (rMDV-HA) was developed under the control of a human CMV immediate-early promoter. The HA expression in the rMDV-HA was tested by immunofluorescence and Western blot analyses, and in vitro and in vivo growth properties of rMDV-HA were also analyzed. Furthermore, we evaluated and compared the protective immunity of rMDV-HA and previously constructed rHVT-HA against HPAIV and lethal MDV. Vaccination of chickens with rMDV-HA induced 80% protection against HPAIV, which was better than the protection rate by rHVT-HA (66.7%). In the animal study with MDV challenge, chickens immunized with rMDV-HA were completely protected against virulent MDV strain J-1 whereas rHVT-HA only induced 80% protection with the same challenge dose. Conclusions/Significance The rMDV-HA vaccine was more effective than rHVT-HA vaccine for protection against lethal MDV and HPAIV challenges. Therefore, avirulent MDV type 1 vaccine is a better vector than HVT for development of a recombinant live virus vaccine against virulent MDV and HPAIV in poultry. PMID:23301062

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

PubMed

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

2016-09-01

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. 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. 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. Continued active surveillance is needed to monitor RVA genotypes in the United States and to detect potential changes since vaccine licensure. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Differences in multiplication of virulent and vaccine strains of poliovirus type I, II, and III in laboratory animals.

PubMed

Koroleva, G A; Lashkevich, V A; Voroshilova, M K

1977-01-01

Multiplication of virulent and vaccine strains of poliovirus type I, II and III in laboratory animals of different species was studied comparatively. The main criterion of virus reproduction was the production of the photoresistant virus progeny after inoculation of the animals with proflavin-photosensitized virus strains. On the whole, virulent poliovirus strains were characterized by replication in a wide range of hosts (monkeys, cotton rats, white mice, guinea pigs, rabbits, chickens, chick embryos), a low infective dose, production of the photoresistant progeny to a high titre, clinically overt disease in some animal species. The vaccine strains multiplied in a norrower range of hosts, had a high infective dose, a low titre of virus progeny, and caused no clinical symptoms of infection. These differences may serve as a marker for differentiation between virulent and attenuated strains in vivo. Administration of guanidine before inoculation of newborn cotton rats completely prevented or delayed by several days the production of photoresistant virus progeny. This fact confirms the stability of the proflavin-poliovirus complex under conditions ruling out virus replication.

Anthrax vaccine antigen-adjuvant formulations completely protect New Zealand white rabbits against challenge with Bacillus anthracis Ames strain spores.

PubMed

Peachman, Kristina K; Li, Qin; Matyas, Gary R; Shivachandra, Sathish B; Lovchik, Julie; Lyons, Rick C; Alving, Carl R; Rao, Venigalla B; Rao, Mangala

2012-01-01

In an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (PA)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using Bacillus anthracis Ames strain spores. The vaccine formulations include PA adsorbed to Alhydrogel, PA encapsulated in liposomes containing monophosphoryl lipid A, stable liposomal PA oil-in-water emulsion, PA displayed on bacteriophage T4 by the intramuscular route, and PA mixed with Escherichia coli heat-labile enterotoxin administered by the needle-free transcutaneous route. Three of the vaccine formulations administered by the intramuscular or the transcutaneous route as a three-dose regimen induced 100% protection in the rabbit model. One of the formulations, liposomal PA, also induced significantly higher lethal toxin neutralizing antibodies than PA-Alhydrogel. Even 5 months after the second immunization of a two-dose regimen, rabbits vaccinated with liposomal PA were 100% protected from lethal challenge with Ames strain spores. In summary, the needle-free skin delivery and liposomal formulation that were found to be effective in two different animal model systems appear to be promising candidates for next-generation anthrax vaccine development.

Immunoproteomic analysis of the human antibody response to natural tularemia infection with Type A or Type B strains or LVS vaccination

PubMed Central

Fulton, Kelly M.; Zhao, Xigeng; Petit, Mireille D.; Kilmury, Sara L.N; Wolfraim, Lawrence A.; House, Robert V.; Sjostedt, Anders; Twine, Susan M.

2011-01-01

Francisella tularensis is pathogenic for many mammalian species including humans, causing a spectrum of diseases called tularemia. The highly virulent Type A strains have associated mortality rates of up to 60% if inhaled. An attenuated live vaccine strain (LVS) is the only vaccine to show efficacy in humans, but suffers several barriers to licensure, including the absence of a correlate of protection. An immunoproteomics approach was used to survey the repertoire of antibodies in sera from individuals who had contracted tularemia during two outbreaks and individuals from two geographical areas who had been vaccinated with NDBR Lot 11 or Lot 17 LVS. These data showed a large overlap in the antibodies generated in response to tularemia infection or LVS vaccination. A total of seven proteins were observed to be reactive with 60 % or more sera from vaccinees and convalescents. A further four proteins were recognised by 30–60 % of the sera screened. These proteins have the potential to serve as markers of vaccination or candidates for subunit vaccines. PMID:21873113

Identification of gyrB and rpoB gene mutations and differentially expressed proteins between a novobiocin-resistant Aeromonas hydrophila catfish vaccine strain and its virulent parent strain

USDA-ARS?s Scientific Manuscript database

Sequence comparison between the full-length 2412 bp DNA gyrase subunit B (gyrB) gene of a novobiocin resistant Aeromonas hydrophila AH11NOVO vaccine strain and that of its virulent parent strain AH11P revealed 10 missense mutations. Similarly, sequence comparison between the full-length 4092 bp RNA ...

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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rapid real-time PCR methods to distinguish Salmonella Enteritidis wildtype field isolates from vaccine strains Salmovac SE/Gallivac SE and AviPro SALMONELLA VAC E.

PubMed

Maurischat, Sven; Szabo, Istvan; Baumann, Beatrice; Malorny, Burkhard

2015-05-01

Salmonella enterica serovar Enteritidis is a major non-typhoid Salmonella serovar causing human salmonellosis mainly associated with the consumption of poultry and products thereof. To reduce infections in poultry, S. Enteritidis live vaccine strains AviPro SALMONELLA VAC E and Salmovac SE/Gallivac SE have been licensed and used in several countries worldwide. To definitively diagnose a S. Enteritidis contamination in vaccinated herds a reliable and fast method for the differentiation between vaccine and wildtype field isolates is required. In this study, we developed and validated real-time PCR (qPCR) assays to distinguish those variants genetically. Suitable target sequences were identified by whole genome sequencing (WGS) using the Illumina MiSeq system. SNP regions in kdpA and nhaA proved to be most useful for differentiation of AviPro SALMONELLA VAC E and Salmovac SE/Gallivac SE, respectively, from wildtype strains. For each vaccine strain one TaqMan-qPCR assay and one alternative approach using High Resolution Melting (HRM) analysis was designed. All 30 Salmovac SE and 7 AviPro SALMONELLA VAC E vaccine strain reisolates tested were correctly identified by both approaches (100% inclusivity). Furthermore, all 137 (TaqMan) and 97 (HRM) Salmonella non-vaccine and related Enterobacteriaceae strains tested were excluded (100% exclusivity). The analytical detection limits were determined to be approx. 10(2) genome copies/reaction for the TaqMan and 10(4) genome copies/reaction for the HRM approach. The real-time PCR assays proved to be a reliable and fast alternative to the cultural vaccine strain identification tests helping decision makers in control measurements to take action within a shorter period of time. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of the thermal stability of a novel strain of live-attenuated mumps vaccine (RS-12 strain) lyophilized in different stabilizers.

PubMed

Jamil, Razieh Kamali; Taqavian, Mohammad; Sadigh, Zohreh-Azita; Shahkarami, Mohammad-Kazem; Esna-Ashari, Fatemeh; Hamkar, Rasool; Hosseini, Seyedeh-Marzieh; Hatami, Alireza

2014-04-01

The stability of live-attenuated viral vaccines is important for immunization efficacy. Here, the thermostabilities of lyophilized live-attenuated mumps vaccine formulations in two different stabilizers, a trehalose dihydrate-based stabilizer and a stabilizer containing sucrose, human serum albumin and sorbitol were investigated using accelerated stability tests at 4°C, 25°C and 37°C at time points between 4h (every 4h for the first 24h) and 1 week. Even under the harshest storage conditions of 37°C for 1 week, the 50% cell culture infective dose (CCID50) determined from titrations in Vero cells dropped by less than 10-fold using each stabilizer formulation and thus complied with the World Health Organization's requirements for the potency of live-attenuated mumps vaccines. However, as the half-life of the RS-12 strain mumps virus infectivity was lengthened substantially at elevated temperatures using the trehalose dihydrate (TD)-based stabilizer, this stabilizer is recommended for vaccine use. Copyright © 2013 Elsevier B.V. All rights reserved.

[Lack of association between thimerosal-containing vaccines and autism].

PubMed

Mrozek-Budzyn, Dorota; Majewska, Renata; Kiełtyka, Agnieszka; Augustyniak, Małgorzata

2011-01-01

In Poland, administered childhood vaccines still contain thimerosal as a preservative. Despite the access to mercury free formulas, the most of children are still vaccinated by thimerosal-containing vaccines (TCV) owing to economical reasons. That circumstances caused the rising discussion on potential harmful influence of TCVs on children health. The objective of this analysis was to determine an association of TCVs exposure with the risk of autism. Study population included 96 cases diagnosed with childhood or atypical autism and 192 controls matched individually by year of birth, gender, and physician's practice. Data on autism diagnose and vaccination history were from GPs. Data on the other possible autism risk factors were collected from mothers. Conditional logistic regression was used to assess the risk of autism due to TCVs exposure. No significant association was found between TCVs exposure and autism. After adjusting to potential confounders, odds ratios of the risk of autism developing for infants vaccinated with TCVs were 1.52 (95% CI: 0.29-11.11) for doses 12.5-87.5 microg, 2.78 (95% CI: 0.29-11.11) for 100-137.5 microg and 1.97 (95% CI: 0.37-18.95) for these exposed > or = 150 microg. Our study revealed no evidence of an association between TCVs and autism.

IL-10 restrains IL-17 to limit lung pathology characteristics following pulmonary infection with Francisella tularensis live vaccine strain.

PubMed

Slight, Samantha R; Monin, Leticia; Gopal, Radha; Avery, Lyndsay; Davis, Marci; Cleveland, Hillary; Oury, Tim D; Rangel-Moreno, Javier; Khader, Shabaana A

2013-11-01

IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10-deficient mice (Il10(-/-)), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10(-/-)-infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Perceived concern about the new strain of the influenza and obtaining the vaccine in China, Japan and South Korea.

PubMed

Kamimura, Akiko; Armenta, Bianca A; Nourian, Maziar M; Wright, Lindsey; Rathi, Naveen; Chernenko, Alla

This study compares the factors, which influence individuals from the countries of China, Japan and South Korea to obtain any type of influenza vaccines and their perceived concerns about the new strain of the influenza - pandemic (H1N1) 2009. The data analyzed was from the East Asian Social Survey (EASS), Cross-National Survey Data Sets: Health and Society in East Asia, 2010 (ICPSR 34608) (N=7938). The results of this study suggest that individuals who are concerned about the new strain of influenza are more likely to have obtained influenza vaccine. In these countries, perceived concerns may be directly related to vaccine-related behaviors. The results of this study also indicate that there are variations within each country regarding as to why individuals do or do not obtain the influenza vaccine. Over all, this project provides new insights about the acquisition of the influenza vaccine within China, Japan and South Korea, which will be useful for medical practice within these countries and future research. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

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.

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

Use of a current varicella vaccine as a live polyvalent vaccine vector.

PubMed

Murakami, Kouki; Mori, Yasuko

2016-01-04

Varicella-zoster virus (VZV) is the causative agent of varicella and zoster. The varicella vaccine was developed to control VZV infection in children. The currently available Oka vaccine strain is the only live varicella vaccine approved by the World Health Organization. We previously cloned the complete genome of the Oka vaccine strain into a bacterial artificial chromosome vector and then successfully reconstituted the virus. We then used this system to generate a recombinant Oka vaccine virus expressing mumps virus gene(s). The new recombinant vaccine may be an effective polyvalent live vaccine that provides protection against both varicella and mumps viruses. In this review, we discussed about possibility of polyvalent live vaccine(s) using varicella vaccine based on our recent studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

2017-05-01

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 LD 50 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 LD 50 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. Copyright © 2017 Elsevier Ltd. All rights reserved.

[The use of anthropologic methods for studying the causes of lack of vaccination. The case of Nativitas, Xochimilco].

PubMed

Nigenda-López, G; Orozco-Núñez, E

1990-01-01

The relationship between the socio-cultural characteristics of a population and their participation in immunization programs is described in this paper. An anthropological approach was utilized to study the reasons why certain population groups do not participate in the immunization programs or do so inadequately. The study was undertaken in a community south of Mexico City. The paper contains the description of the community's contextual elements, the organization of the medical care services and the participation of the population in the immunization programs. It was found that a wide millieu of socio-cultural factors are related with people's behavior toward vaccination, such as: lack of information about diseases and vaccines, lack of trust on modern health services, and the strong influence of traditional medicine. Clear implications can be derived from the analysis with regards to the need for revision and modification of strategies of the health education programs, in order to promote a wider participation in immunization programs.

Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine.

PubMed

Rossi, Raffaella; Beernink, Peter T; Giuntini, Serena; Granoff, Dan M

2015-12-01

In 2013 and 2014, two U.S. universities had meningococcal serogroup B outbreaks (a total of 14 cases) caused by strains from two different clonal complexes. To control the outbreaks, students were immunized with a serogroup B meningococcal vaccine (Novartis) that was not yet licensed in the United States. The vaccine (referred to as MenB-4C) contains four components capable of eliciting bactericidal activity. Both outbreak strains had high expression levels of two of the vaccine antigens (subfamily B factor H binding protein [FHbp] and neisserial heparin binding antigen [NHba]); the university B outbreak strain also had moderate expression of a third antigen, NadA. We investigated the bactericidal activity of sera from mice immunized with FHbp, NHba, or NadA and sera from MenB-4C-immunized infant macaques and an adult human. The postimmunization bactericidal activity of the macaque or human serum against isolates from university B with FHbp identification (ID) 1 that exactly matched the vaccine FHbp sequence variant was 8- to 21-fold higher than that against isolates from university A with FHbp ID 276 (96% identity to the vaccine antigen). Based on the bactericidal activity of mouse antisera to FHbp, NadA, or NHba and macaque or human postimmunization serum that had been depleted of anti-FHbp antibody, the bactericidal activity against both outbreak strains largely or entirely resulted from antibodies to FHbp. Thus, despite the high level of strain expression of FHbp from a subfamily that matched the vaccine antigen, there can be large differences in anti-FHbp bactericidal activity induced by MenB-4C vaccination. Further, strains with moderate to high NadA and/or NHba expression can be resistant to anti-NadA or anti-NHba bactericidal activity elicited by MenB-4C vaccination. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Universal varicella vaccine immunization in Japan.

PubMed

Yoshikawa, Tetsushi; Kawamura, Yoshiki; Ohashi, Masahiro

2016-04-07

In 1974, Japanese scientists developed a live attenuated varicella vaccine based on the Oka strain. The efficacy of the vaccine for the prevention of varicella has been primarily demonstrated in studies conducted in the United States following the adoption of universal immunization using the Oka strain varicella vaccine in 1996. Although the vaccine was developed by Japanese scientists, until recently, the vaccine has been administered on a voluntary basis in Japan resulting in a vaccine coverage rate of approximately 40%. Therefore, Japan initiated universal immunization using the Oka strain varicella vaccine in November 2014. Given the transition from voluntary to universal immunization in Japan, it will also be important to monitor the epidemiology of varicella and herpes zoster. The efficacy and safety of co-administration of the varicella vaccine and measles, mumps, and rubella vaccine have been demonstrated in many countries; however, there was no data from Japan. In order to adopt the practice of universal immunization using the Oka strain varicella vaccine in Japan, data demonstrating the efficacy and safety of co-administration of varicella vaccine and measles and rubella (MR) vaccine were required. Additionally, we needed to elucidate the appropriate time interval between the first and second administrations of the vaccine. It is also important to differentiate between wild type and Oka vaccine type strains in herpes zoster patient with past history of varicella vaccine. Thus, there are many factors to consider regarding the adoption of universal immunization in Japan to control varicella zoster virus (VZV) infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunity status of adults and children against poliomyelitis virus type 1 strains CHAT and Sabin (LSc-2ab) in Germany.

PubMed

Eggers, Maren; Terletskaia-Ladwig, Elena; Rabenau, Holger F; Doerr, Hans W; Diedrich, Sabine; Enders, Gisela; Enders, Martin

2010-12-09

In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster. Neutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines. The neutralisation activity against CHAT in adults with OPV vaccination history was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P < 0.025). In eight sera, the antibody titres measured against CHAT were less than 8, although the titre against Sabin 1 varied between 8 and 64. Following IPV booster, anti-CHAT antibodies increased rapidly in sera of CHAT-negative adults with OPV history. Sera from children with IPV history neutralised CHAT and Sabin 1 strains equally. The lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We strongly suggest that laboratory

Vaccine Candidates against Nontypeable Haemophilus influenzae: a Review

PubMed Central

Behrouzi, Ava; Vaziri, Farzam; Rahimi-Jamnani, Fatemeh; Afrough, Parviz; Rahbar, Mohammad; Satarian, Fereshteh; Siadat, Seyed Davar

2017-01-01

Nonencapsulated, nontypeable Hemophilus influenzae (NTHi) remains an important cause of acute otitis and respiratory diseases in children and adults. NTHi bacteria are one of the major causes of respiratory tract infections, including acute otitis media, cystic fibrosis, and community-acquired pneumonia among children, especially in developing countries. The bacteria can also cause chronic diseases such as chronic bronchitis and chronic obstructive pulmonary disease in the lower respiratory tract of adults. Such bacteria express several outer membrane proteins, some of which have been studied as candidates for vaccine development. Due to the lack of effective vaccines as well as the spread and prevalence of NTHi worldwide, there is an urgent need to design and develop effective vaccine candidates against these strains. PMID:28088130

Uptake and impact of vaccinating school age children against influenza during a season with circulation of drifted influenza A and B strains, England, 2014/15.

PubMed

Pebody, Richard G; Green, Helen K; Andrews, Nick; Boddington, Nicola L; Zhao, Hongxin; Yonova, Ivelina; Ellis, Joanna; Steinberger, Sophia; Donati, Matthew; Elliot, Alex J; Hughes, Helen E; Pathirannehelage, Sameera; Mullett, David; Smith, Gillian E; de Lusignan, Simon; Zambon, Maria

2015-01-01

The 2014/15 influenza season was the second season of roll-out of a live attenuated influenza vaccine (LAIV) programme for healthy children in England. During this season, besides offering LAIV to all two to four year olds, several areas piloted vaccination of primary (4-11 years) and secondary (11-13 years) age children. Influenza A(H3N2) circulated, with strains genetically and antigenically distinct from the 2014/15 A(H3N2) vaccine strain, followed by a drifted B strain. We assessed the overall and indirect impact of vaccinating school age children, comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot to non-pilot areas. Uptake levels were 56.8% and 49.8% in primary and secondary school pilot areas respectively. In primary school age pilot areas, cumulative primary care influenza-like consultation, emergency department respiratory attendance, respiratory swab positivity, hospitalisation and excess respiratory mortality were consistently lower in targeted and non-targeted age groups, though less for adults and more severe end-points, compared with non-pilot areas. There was no significant reduction for excess all-cause mortality. Little impact was seen in secondary school age pilot only areas compared with non-pilot areas. Vaccination of healthy primary school age children resulted in population-level impact despite circulation of drifted A and B influenza strains.

Lack of nonspecific protection against all-cause nonrotavirus gastroenteritis by vaccination with orally administered rotavirus vaccine.

PubMed

Grant, Lindsay; Watt, James; Moulton, Lawrence; Weatherholtz, Robert; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine

2013-06-01

Acute gastroenteritis (AGE) is recognized as a global, common threat to child survival, especially in developing countries. Rotavirus, in particular, has been implicated as a leading cause of severe AGE; however, there are numerous other pathogens that also cause AGE. Several studies have demonstrated that oral vaccination against rotavirus has generated the unanticipated benefit of protecting against AGE caused by nonrotavirus pathogens. Safety and efficacy of the pentavalent bovine-human reassortant rotavirus vaccine were studied in multiple populations, including children of the Navajo and White Mountain Apache tribes in the southwestern United States. Stool specimens were collected from children with AGE and tested for rotavirus using an enzyme immunoassay. Analyses were conducted to detect the presence or absence of a vaccine effect on incidence, severity, and duration of AGE in which rotavirus was not detected. The majority of AGE (N = 558: 472 nonrotavirus vs 86 rotavirus) occurred between August 2002 and March 2004 among children ranging from ages 4 to 23 months. The incidence of nonrotavirus AGE was similar by vaccine groups with an incidence rate ratio of 1.07 (incidence rate ratio = vaccinated/unvaccinated, 95% confidence interval 0.89-1.29). The hazards of first, second, third, or any AGE in which rotavirus was not detected differed little by vaccination status (P > 0.05). Duration of symptoms and severity of nonrotavirus AGE were similar by vaccine group. There was no vaccine effect on frequency or severity of nonrotavirus AGE.

Human rotavirus strains circulating in Venezuela after vaccine introduction: predominance of G2P[4] and reemergence of G1P[8].

PubMed

Vizzi, Esmeralda; Piñeros, Oscar A; Oropeza, M Daniela; Naranjo, Laura; Suárez, José A; Fernández, Rixio; Zambrano, José L; Celis, Argelia; Liprandi, Ferdinando

2017-03-21

Rotavirus (RV) is the most common cause of severe childhood diarrhea worldwide. Despite Venezuela was among the first developing countries to introduce RV vaccines into their national immunization schedules, RV is still contributing to the burden of diarrhea. Concerns exist about the selective pressure that RV vaccines could exert on the predominant types and/or emergence of new strains. To assess the impact of RV vaccines on the genotype distribution 1 year after the vaccination was implemented, a total of 912 fecal specimens, collected from children with acute gastroenteritis in Caracas from February 2007 to April 2008, were screened, of which 169 (18.5%) were confirmed to be RV positive by PAGE. Rotavirus-associated diarrhea occurred all year-round, although prevailed during the coolest and driest months among unvaccinated children under 24 months old. Of 165 RV strains genotyped for G (VP7) and P (VP4) by seminested multiplex RT-PCR, 77 (46.7%) were G2P[4] and 63 (38.2%) G1P[8]. G9P[8], G3P[8] and G2P[6] were found in a lower proportion (7.3%). Remarkable was also the detection of <5% of uncommon combinations (G8P[14], G8P[4], G1P[4] and G4P[4]) and 3.6% of mixed infections. A changing pattern of G/P-type distribution was observed during the season studied, with complete predominance of G2P[4] from February to June 2007 followed by its gradual decline and the reemergence of G1P[8], predominant since January 2008. Phylogenetic analysis of VP7 and VP4 genes revealed a high similarity among G2P[4] and global strains belonging to G2-II and P[4]-V lineages. The amino acid substitution 96D → N, related with reemergence of the G2 genotype elsewhere, was observed. The G1P[8] strains from Caracas were grouped into the lineages G1-I and P[8]-III, along with geographically remote G1P[8] rotaviruses, but they were rather distant from Rotarix ® vaccine and pre-vaccine strains. Unique amino acid substitutions observed on neutralization domains of the VP7 sequence from

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preliminary assessment of the safety and immunogenicity of live oral cholera vaccine strain CVD 103-HgR in healthy Thai adults.

PubMed Central

Migasena, S; Pitisuttitham, P; Prayurahong, B; Suntharasamai, P; Supanaranond, W; Desakorn, V; Vongsthongsri, U; Tall, B; Ketley, J; Losonsky, G

1989-01-01

A single dose (5 x 10(8) organisms) of attenuated A- B+ Vibrio cholerae classical Inaba recombinant vaccine strain CVD 103-HgR or placebo was administered to 24 healthy young Thai adults in a randomized, placebo-controlled, double-blind trial of safety and immunogenicity. None of the volunteers experienced untoward reactions. The vaccine strain was recovered from 2 of 12 vaccines. The vibriocidal antibody response (the best immunological correlate of protection) was good: 11 of 12 vaccinees (92%) manifested significant serotype-homologous Inaba antibody rises with a peak reciprocal geometric mean titer (RGMT) postvaccination of 3,417; 9 of 12 exhibited significant serotype-heterologous Ogawa antibody rises (prevaccination RGMT, 180; peak RGMT, 2,874). Nine of 12 vaccinees had significant rises in serum antitoxin. None of the controls exhibited rises in vibriocidal or antitoxic antibody. This preliminary study further confirms the safety and immunogenicity of CVD 103-HgR live oral cholera vaccine and paves the way for larger community studies of this candidate cholera vaccine. PMID:2807523

[Dynamics of cytokine production in adults after administration of influenza vaccine from A/California/7/2009 (H1N1) strain].

PubMed

Terkacheva, O A; Kostinov, M P; Zhirova, S N; Cherdantsev, A P

2012-01-01

Study dynamics of IFNalpha, IFNgamma, TNFalpha cytokines in healthy adults after administration of inactivated subunit monovalent influenza vaccine, A/California/7/2009 (H1N1) strain. Levels of IFNalpha, IFNgamma, TNFalpha cytokines were studied in blood sera of 58 mostly healthy adults aged 18 - 60 years. Kits for enzyme immunoassay determination of cytokine levels (Vector-Best, Novosibirsk) were used in the study. Antibody titers to A/California/7/2009 (H1N1) strain were determined at analogous time by using microneutralization reaction (MNR). Changes in the level of IFNalpha, IFNgamma, TNFalpha in healthy volunteers immunized by pandemic influenza vaccine were evaluated. Vaccine was safe. Two immunizations did not result in an increase of TNFalpha level that is an additional evidence of vaccine safety. IFNalpha level had a tendency to increase in vaccinated volunteers. IFNgamma levels in volunteers with normal level of this cytokine (below 10 pg/ml) were increased significantly after the second immunization (from 2.66 +/- 2.48 to 5.21 +/- 2.56). Correlation analysis showed that there is a strong negative association between IFNalpha, IFNgamma and seroconversion.

Antigenic and genetic comparison of foot-and-mouth disease virus serotype O Indian vaccine strain, O/IND/R2/75 against currently circulating viruses.

PubMed

Mahapatra, Mana; Yuvaraj, S; Madhanmohan, M; Subramaniam, S; Pattnaik, B; Paton, D J; Srinivasan, V A; Parida, Satya

2015-01-29

Foot-and-mouth disease (FMD) virus serotype O is the most common cause of FMD outbreaks in India and three of the six lineages that have been described are most frequently detected, namely Ind2001, PanAsia and PanAsia 2. We report the full capsid sequence of 21 serotype O viruses isolated from India between 2002 and 2012. All these viruses belong to the Middle East-South Asia (ME-SA) topotype. The serological cross-reactivity of a bovine post-vaccination serum pool raised against the current Indian vaccine strain, O/IND/R2/75,was tested by virus neutralisation test with the 23 Indian field isolates, revealing a good match between the vaccine and the field isolates. The cross reactivity of the O/IND/R2/75 vaccine with 19 field isolates from other countries (mainly from Asia and Africa) revealed a good match to 79% of the viruses indicating that the vaccine strain is broadly cross-reactive and could be used to control FMD in other countries. Comparison of the capsid sequences of the serologically non-matching isolates with the vaccine strain sequence identified substitutions in neutralising antigenic sites 1 and 2, which could explain the observed serological differences. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Antigenic and genetic comparison of foot-and-mouth disease virus serotype O Indian vaccine strain, O/IND/R2/75 against currently circulating viruses

PubMed Central

Mahapatra, Mana; Yuvaraj, S.; Madhanmohan, M.; Subramaniam, S.; Pattnaik, B.; Paton, D.J.; Srinivasan, V.A.; Parida, Satya

2015-01-01

Foot-and-mouth disease (FMD) virus serotype O is the most common cause of FMD outbreaks in India and three of the six lineages that have been described are most frequently detected, namely Ind2001, PanAsia and PanAsia 2. We report the full capsid sequence of 21 serotype O viruses isolated from India between 2002 and 2012. All these viruses belong to the Middle East–South Asia (ME–SA) topotype. The serological cross-reactivity of a bovine post-vaccination serum pool raised against the current Indian vaccine strain, O/IND/R2/75,was tested by virus neutralisation test with the 23 Indian field isolates, revealing a good match between the vaccine and the field isolates. The cross reactivity of the O/IND/R2/75 vaccine with 19 field isolates from other countries (mainly from Asia and Africa) revealed a good match to 79% of the viruses indicating that the vaccine strain is broadly cross-reactive and could be used to control FMD in other countries. Comparison of the capsid sequences of the serologically non-matching isolates with the vaccine strain sequence identified substitutions in neutralising antigenic sites 1 and 2, which could explain the observed serological differences. PMID:25500306

Characterization and vaccine potential of outer membrane vesicles produced by Haemophilus parasuis

DOE PAGES

McCaig, William D.; Loving, Crystal L.; Hughes, Holly R.; ...

2016-03-01

Haemophilus parasuis is a Gram-negative bacterium that colonizes the upper respiratory tract of swine and is capable of causing a systemic infection, resulting in high morbidity and mortality. H. parasuis isolates display a wide range of virulence and virulence factors are largely unknown. Commercial bacterins are often used to vaccinate swine against H. parasuis, though strain variability and lack of cross-reactivity can make this an ineffective means of protection. Outer membrane vesicles (OMV) are spherical structures naturally released from the membrane of bacteria and OMV are often enriched in toxins, signaling molecules and other bacterial components. Examination of OMV structuresmore » has led to identification of virulence factors in a number of bacteria and they have been successfully used as subunit vaccines. We have isolated OMV from both virulent and avirulent strains of H. parasuis, have examined their protein content and assessed their ability to induce an immune response in the host. Lastly, vaccination with purified OMV derived from the virulent H. parasuis Nagasaki strain provided protection against challenge with a lethal dose of the bacteria.« less

Characterization and vaccine potential of outer membrane vesicles produced by Haemophilus parasuis

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCaig, William D.; Loving, Crystal L.; Hughes, Holly R.

Haemophilus parasuis is a Gram-negative bacterium that colonizes the upper respiratory tract of swine and is capable of causing a systemic infection, resulting in high morbidity and mortality. H. parasuis isolates display a wide range of virulence and virulence factors are largely unknown. Commercial bacterins are often used to vaccinate swine against H. parasuis, though strain variability and lack of cross-reactivity can make this an ineffective means of protection. Outer membrane vesicles (OMV) are spherical structures naturally released from the membrane of bacteria and OMV are often enriched in toxins, signaling molecules and other bacterial components. Examination of OMV structuresmore » has led to identification of virulence factors in a number of bacteria and they have been successfully used as subunit vaccines. We have isolated OMV from both virulent and avirulent strains of H. parasuis, have examined their protein content and assessed their ability to induce an immune response in the host. Lastly, vaccination with purified OMV derived from the virulent H. parasuis Nagasaki strain provided protection against challenge with a lethal dose of the bacteria.« less

Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes Multiple Individual Wild and Vaccine-Derived Polioviruses.

PubMed

Sun, Mingbo; Li, Changgui; Xu, Wenbo; Liao, Guoyang; Li, Rongcheng; Zhou, Jian; Li, Yanping; Cai, Wei; Yan, Dongmei; Che, Yanchun; Ying, Zhifang; Wang, Jianfeng; Yang, Huijuan; Ma, Yan; Ma, Lei; Ji, Guang; Shi, Li; Jiang, Shude; Li, Qihan

2017-05-15

A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is the rational option for completely eradicating poliovirus transmission. The neutralizing capacity of Sabin-IPV immune serum to different strains of poliovirus is a key indicator of the clinical protective efficacy of this vaccine. Sera collected from 500 infants enrolled in a randomized, blinded, positive control, phase 2 clinical trial were randomly divided into 5 groups: Groups A, B, and C received high, medium, and low doses, respectively, of Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk strain-based IPV, respectively, all on the same schedule. Immune sera were collected after the third dose of primary immunization, and tested in cross-neutralization assays against 19 poliovirus strains of all 3 types. All immune sera from all 5 groups interacted with the 19 poliovirus strains with various titers and in a dose-dependent manner. One type 2 immunodeficiency-associated vaccine-derived poliovirus strain was not recognized by these immune sera. Sabin-IPV vaccine can induce protective antibodies against currently circulating and reference wild poliovirus strains and most vaccine-derived poliovirus strains, with rare exceptions. NCT01056705. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Measles inclusion-body encephalitis caused by the vaccine strain of measles virus.

PubMed

Bitnun, A; Shannon, P; Durward, A; Rota, P A; Bellini, W J; Graham, C; Wang, E; Ford-Jones, E L; Cox, P; Becker, L; Fearon, M; Petric, M; Tellier, R

1999-10-01

We report a case of measles inclusion-body encephalitis (MIBE) occurring in an apparently healthy 21-month-old boy 8.5 months after measles-mumps-rubella vaccination. He had no prior evidence of immune deficiency and no history of measles exposure or clinical disease. During hospitalization, a primary immunodeficiency characterized by a profoundly depressed CD8 cell count and dysgammaglobulinemia was demonstrated. A brain biopsy revealed histopathologic features consistent with MIBE, and measles antigens were detected by immunohistochemical staining. Electron microscopy revealed inclusions characteristic of paramyxovirus nucleocapsids within neurons, oligodendroglia, and astrocytes. The presence of measles virus in the brain tissue was confirmed by reverse transcription polymerase chain reaction. The nucleotide sequence in the nucleoprotein and fusion gene regions was identical to that of the Moraten and Schwarz vaccine strains; the fusion gene differed from known genotype A wild-type viruses.

Influence of vaccine strains on the evolution of canine distemper virus.

PubMed

da Fontoura Budaszewski, Renata; Streck, André Felipe; Nunes Weber, Matheus; Maboni Siqueira, Franciele; Muniz Guedes, Rafael Lucas; Wageck Canal, Cláudio

2016-07-01

Canine distemper virus (CDV) is a major dog pathogen belonging to the genus Morbillivirus of the family Paramyxoviridae. CDV causes disease and high mortality in dogs and wild carnivores. Although homologous recombination has been demonstrated in many members of Paramyxoviridae, these events have rarely been reported for CDV. To detect potential recombination events, the complete CDV genomes available in GenBank up to June 2015 were screened using distinct algorithms to detect genetic conversions and incongruent phylogenies. Eight putative recombinant viruses derived from different CDV genotypes and different hosts were detected. The breakpoints of the recombinant strains were primarily located on fusion and hemagglutinin glycoproteins. These results suggest that homologous recombination is a frequent phenomenon in morbillivirus populations under natural replication, and CDV vaccine strains might play an important role in shaping the evolution of this virus.

Safety and immunogenicity of inactivated poliovirus vaccine based on Sabin strains with and without aluminum hydroxide: a phase I trial in healthy adults.

PubMed

Verdijk, Pauline; Rots, Nynke Y; van Oijen, Monique G C T; Oberste, M Steven; Boog, Claire J; Okayasu, Hiromasa; Sutter, Roland W; Bakker, Wilfried A M

2013-11-12

An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle income countries in the context of the Global Polio Eradication Initiative. Safety and immunogenicity of the Sabin-IPV was evaluated in a double-blind, randomized, controlled, phase I 'proof-of-concept' trial. Healthy male adults received a single intramuscular injection with Sabin-IPV, Sabin-IPV adjuvanted with aluminum hydroxide or conventional IPV. Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after vaccination. No vaccine-related serious adverse events were observed, and all local and systemic reactions were mild or moderate and transient. In all subjects, an increase in antibody titer for all types of poliovirus (both Sabin and wild strains) was observed 28 days after vaccination. Sabin-IPV and Sabin-IPV adjuvanted with aluminum hydroxide administered as a booster dose were equally immunogenic and safe as conventional IPV. EudraCTnr: 2010-024581-22, NCT01708720. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influenza A virus vaccines for swine.

PubMed

Vincent, Amy L; Perez, Daniel R; Rajao, Daniela; Anderson, Tavis K; Abente, Eugenio J; Walia, Rasna R; Lewis, Nicola S

2017-07-01

Economic losses due to influenza A virus (IAV) infections are substantial and a global problem, ranking among the top three major health challenges in the swine industry. Currently, H1 and H3 subtypes circulate in pigs globally associated with different combinations of N1 and N2 subtypes; however, the origin, gene constellation, and antigenic makeup of IAV vary greatly on different continents. Vaccination is one means of mitigating the effects of IAV disease, and vaccines are most effective if the strains included closely match the currently circulating strains in pigs. Genetic analyses provide panoramic views of the virus landscape at the sequence level and, thus, can aid in the selection of well-matched swine IAV vaccine strains, but is not sufficient alone. Additionally, a major challenge in selecting appropriate swine IAV vaccine strains is the co-circulation of multiple lineages of viruses in the same region, requiring multivalent or broadly cross-reacting antigens. Due to this complex IAV ecology in swine, new vaccination strategies and vaccine platforms are needed. The hemagglutinin (HA) viral protein is the major target of neutralizing antibodies, which are widely considered to be correlated with protection. Virus variants that are not recognized by previously elicited antibodies can render traditional vaccines that primarily elicit humoral responses ineffective, and therefore result in the need for vaccine strain reformulation and re-vaccination. In the future, new vaccine platforms may be on the market that will provide alternative options to those currently available. Nonetheless, a collaborative approach is needed to improve IAV vaccine strain selection for use in swine. Published by Elsevier B.V.

Oral vaccination with a live Salmonella Enteritidis/Typhimurium bivalent vaccine in layers induces cross-protection against caecal and internal organ colonization by a Salmonella Infantis strain.

PubMed

Eeckhaut, Venessa; Haesebrouck, Freddy; Ducatelle, Richard; Van Immerseel, Filip

2018-05-01

Salmonella is an important zoonotic agent, and poultry products remain one of the main sources of infection for humans. Salmonella Infantis is an emerging serotype in poultry worldwide, reflected by an increased prevalence in poultry flocks, on broiler meat and in human foodborne illness cases. In the current study, the efficacy of oral administration of a live monovalent Salmonella Enteritidis and a live bivalent Salmonella Enteritidis/Typhimurium vaccine, against a Salmonella Enteritidis and Infantis infection, was determined. Oral administration of the live vaccines to day-old chickens caused a decrease in caecal colonization by Salmonella Enteritidis, but not Infantis, at day 7, when challenged at day 2. Vaccination with the bivalent vaccine at day 1 resulted in a decreased spleen colonization by both Salmonella Infantis and Enteritidis. Twice (at day 1 and week 6) and thrice vaccination (at day 1, week 6 and 16) of laying hens with the bivalent vaccine resulted in a decreased caecal colonization by Salmonella Enteritidis and Infantis, and significantly lower oviduct colonization levels by Salmonella Enteritidis. These data show cross-protection against Salmonella Infantis by oral administration of live vaccine strains belonging to other serogroups. Copyright © 2018 Elsevier B.V. All rights reserved.

Interleukin-17 protects against the Francisella tularensis live vaccine strain but not against a virulent F. tularensis type A strain.

PubMed

Skyberg, Jerod A; Rollins, Maryclare F; Samuel, Joshua W; Sutherland, Marjorie D; Belisle, John T; Pascual, David W

2013-09-01

Francisella tularensis is a highly infectious intracellular bacterium that causes the zoonotic infection tularemia. While much literature exists on the host response to F. tularensis infection, the vast majority of work has been conducted using attenuated strains of Francisella that do not cause disease in humans. However, emerging data indicate that the protective immune response against attenuated F. tularensis versus F. tularensis type A differs. Several groups have recently reported that interleukin-17 (IL-17) confers protection against the live vaccine strain (LVS) of Francisella. While we too have found that IL-17Rα(-/-) mice are more susceptible to F. tularensis LVS infection, our studies, using a virulent type A strain of F. tularensis (SchuS4), indicate that IL-17Rα(-/-) mice display organ burdens and pulmonary gamma interferon (IFN-γ) responses similar to those of wild-type mice following infection. In addition, oral LVS vaccination conferred equivalent protection against pulmonary challenge with SchuS4 in both IL-17Rα(-/-) and wild-type mice. While IFN-γ was found to be critically important for survival in a convalescent model of SchuS4 infection, IL-17 neutralization from either wild-type or IFN-γ(-/-) mice had no effect on morbidity or mortality in this model. IL-17 protein levels were also higher in the lungs of mice infected with the LVS rather than F. tularensis type A, while IL-23p19 mRNA expression was found to be caspase-1 dependent in macrophages infected with LVS but not SchuS4. Collectively, these results demonstrate that IL-17 is dispensable for host immunity to type A F. tularensis infection, and that induced and protective immunity differs between attenuated and virulent strains of F. tularensis.

Development, validation and field evaluation of a quantitative real-time PCR able to differentiate between field Mycoplasma synoviae and the MS-H-live vaccine strain.

PubMed

Dijkman, R; Feberwee, A; Landman, W J M

2017-08-01

A quantitative PCR (qPCR) able to differentiate between field Mycoplasma synoviae and MS-H vaccine strain was developed, validated and evaluated. It was developed using nucleotide differences in the obg gene. Analytical specificity and sensitivity assessed using DNA from 194 M. synoviae field samples, three different batches of MS-H vaccine and from 43 samples representing four other avian Mycoplasma species proved to be 100%. The detection limit for field M. synoviae and MS-H vaccine strain was 10 2-3 and 10 2 colony-forming units PCR equivalents/g trachea mucus, respectively. The qPCR was able to detect both, field M. synoviae and MS-H vaccine strain in ratios of 1:100 determined both using spiked and field samples. One hundred and twenty samples from M. synoviae-infected non-vaccinated birds, 110 samples from M. synoviae-vaccinated birds from a bird experiment and 224 samples from M. synoviae negative (serology and PCR) birds were used to determine the relative sensitivity and specificity using a previously described M. synoviae PCR as reference. The relative sensitivity and specificity for field M. synoviae were 95.0% and 99.6%, respectively, and 94.6% and 100% for the MS-H-live vaccine, respectively. Field validation and confirmation by multi locus sequence typing revealed that the qPCR correctly distinguished between MS-H and field M. synoviae. Evaluation of the differentiating M. synoviae qPCR in three commercial flocks suggested transmission of MS-H-live vaccine from vaccinated to non-vaccinated flocks at the same farm. Furthermore, it showed evidence for the colonization with field M. synoviae in MS-H-vaccinated flocks.

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.

Genetically Engineered, Live Attenuated Vaccines Protect Nonhuman Primates Against Aerosol Challenge with a Virulent IE Strain of Venezuelan Equine Encephalitis Virus

DTIC Science & Technology

2005-01-21

integrated moving average ( ARIMA ) model [15,19]. Fore- casted values for the postexposure time periods were based on the training model extrapolated...Smith JF. Genetically engineered, live attenuated vaccines or Venezuelan equine encephalitis: testing in animal models . Vaccine 2003;21(25–26):3854–62...encephalitis: testing in animal models . Vaccine 2003;21(25-26):3854-62] and IE strains of VEE viruses. 15. SUBJECT TERMS Venezuelan equine

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...

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence.

PubMed

Belongia, Edward A; Skowronski, Danuta M; McLean, Huong Q; Chambers, Catharine; Sundaram, Maria E; De Serres, Gaston

2017-07-01

Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010-11 through 2014-15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014-15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations.

Evaluation of 793/B-like and Mass-like vaccine strain kinetics in experimental and field conditions by real-time RT-PCR quantification.

PubMed

Tucciarone, C M; Franzo, G; Berto, G; Drigo, M; Ramon, G; Koutoulis, K C; Catelli, E; Cecchinato, M

2018-01-01

Infectious bronchitis virus (IBV) is a great economic burden both for productive losses and costs of the control strategies. Many different vaccination protocols are applied in the same region and even in consecutive cycles on the same farm in order to find the perfect balance between costs and benefits. In Northern Italy, the usual second vaccination is more and more often moved up to the chick's first d of life. The second strain administration together with the common Mass priming by spray at the hatchery allows saving money and time and reducing animal stress. The present work compared the different vaccine strains (Mass-like or B48, and 1/96) kinetics both in field conditions and in a 21-day-long experimental trial in broilers, monitoring the viral replication by upper respiratory tract swabbing and vaccine specific real time reverse transcription PCR (RT-PCR) quantification. In both field and experimental conditions, titers for all the vaccines showed an increasing trend in the first 2 wk and then a decrease, though still remaining detectable during the whole monitored period. IBV field strain and avian Metapneumovirus (aMPV) presence also was also investigated by RT-PCR and sequencing, and by multiplex real-time RT-PCR, respectively, revealing a consistency in the pathogen introduction timing at around 30 d, in correspondence with the vaccine titer's main decrease. These findings suggest the need for an accurate knowledge of live vaccine kinetics, whose replication can compete with the other pathogen one, providing additional protection to be added to what is conferred by the adaptive immune response. © 2017 Poultry Science Association Inc.

Virus-Vectored Influenza Virus Vaccines

PubMed Central

Tripp, Ralph A.; Tompkins, S. Mark

2014-01-01

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus).

PubMed

Munang'andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

2016-12-13

Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia ( Niloticus oreochromis ) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy.

An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus)

PubMed Central

Munang’andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

2016-01-01

Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia (Niloticus oreochromis) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy. PMID:27983591

Comparative safety, immunogenicity, and efficacy of several anti-H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine).

PubMed

Gambaryan, Alexandra S; Lomakina, Natalia F; Boravleva, Elizaveta Y; Kropotkina, Ekaterina A; Mashin, Vadim V; Krasilnikov, Igor V; Klimov, Alexander I; Rudenko, Larisa G

2012-05-01

Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non-glycoprotein genes of the experimental live vaccines were from H2N2 cold-adapted master strain A/Leningrad/134/17/57 (VN-Len and Ku-Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN-Gull and Ku-Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold-adapted H1N1 vaccine reduced the mortality near to zero level. The high yield, safety, and protectivity of VN-Len and Ku-Len made them promising strains for the production of inactivated and live vaccines against H5N1 viruses. © 2011 Blackwell Publishing Ltd.

Fluzone® Intradermal Quadrivalent Influenza Vaccine.

PubMed

Robertson, Corwin A; Tsang, Peter; Landolfi, Victoria A; Greenberg, David P

2016-10-01

An intradermal version of Fluzone® split-virion inactivated trivalent influenza vaccine, containing 9 µg hemagglutinin per strain of A/H1N1, A/H3N2, and one B lineage virus (Fluzone Intradermal, Sanofi Pasteur), became available in the US during the 2011-2012 influenza season for adults 18-64 years of age. In advance of the 2015-2016 season, Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine, which contains 9 µg hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata). This literature review summarizes the history and mechanism of intradermal vaccination, discusses the clinical trial results supporting the immunogenicity and safety of Fluzone Intradermal Quadrivalent vaccine, and describes the unique microinjection system used to deliver Fluzone Intradermal Quadrivalent. Expert commentary: Fluzone Intradermal Quadrivalent may boost confidence in influenza vaccination with the addition of a second B-lineage strain. By using an innovative microinjection system, the vaccine is also designed to address some of the logistic challenges faced by healthcare providers administering immunizations.

New vaccines against influenza virus

PubMed Central

Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Yu-Na; Kim, Min-Chul; Kwon, Young-Man; Tang, Yinghua; Cho, Min-Kyoung; Lee, Youn-Jeong

2014-01-01

Vaccination is one of the most effective and cost-benefit interventions that prevent the mortality and reduce morbidity from infectious pathogens. However, the licensed influenza vaccine induces strain-specific immunity and must be updated annually based on predicted strains that will circulate in the upcoming season. Influenza virus still causes significant health problems worldwide due to the low vaccine efficacy from unexpected outbreaks of next epidemic strains or the emergence of pandemic viruses. Current influenza vaccines are based on immunity to the hemagglutinin antigen that is highly variable among different influenza viruses circulating in humans and animals. Several scientific advances have been endeavored to develop universal vaccines that will induce broad protection. Universal vaccines have been focused on regions of viral proteins that are highly conserved across different virus subtypes. The strategies of universal vaccines include the matrix 2 protein, the hemagglutinin HA2 stalk domain, and T cell-based multivalent antigens. Supplemented and/or adjuvanted vaccination in combination with universal target antigenic vaccines would have much promise. This review summarizes encouraging scientific advances in the field with a focus on novel vaccine designs. PMID:24427759

Development of a multiplex amplification refractory mutation system reverse transcription polymerase chain reaction assay for the differential diagnosis of Feline leukemia virus vaccine and wild strains.

PubMed

Ho, Chia-Fang; Chan, Kun-Wei; Yang, Wei-Cheng; Chiang, Yu-Chung; Chung, Yang-Tsung; Kuo, James; Wang, Chi-Young

2014-07-01

A multiplex amplification refractory mutation system reverse transcription polymerase chain reaction (ARMS RT-PCR) was developed for the differential diagnosis of Feline leukemia virus (FeLV) vaccine and wild-type strains based on a point mutation between the vaccine strain (S) and the wild-type strain (T) located in the p27 gene. This system was further upgraded to obtain a real-time ARMS RT-PCR (ARMS qRT-PCR) with a high-resolution melt analysis (HRMA) platform. The genotyping of various strains of FeLV was determined by comparing the HRMA curves with the defined wild-type FeLV (strain TW1), and the results were expressed as a percentage confidence. The detection limits of ARMS RT-PCR and ARMS qRT-PCR combined with HRMA were 100 and 1 copies of transcribed FeLV RNA per 0.5 ml of sample, respectively. No false-positive results were obtained with 6 unrelated pathogens and 1 feline cell line. Twelve FeLV Taiwan strains were correctly identified using ARMS qRT-PCR combined with HRMA. The genotypes of the strains matched the defined FeLV wild-type strain genotype with at least 91.17% confidence. A higher degree of sequence polymorphism was found throughout the p27 gene compared with the long terminal repeat region. In conclusion, the current study describes the phylogenetic relationship of the FeLV Taiwan strains and demonstrates that the developed ARMS RT-PCR assay is able to be used to detect the replication of a vaccine strain that has not been properly inactivated, thus acting as a safety check for the quality of FeLV vaccines.

Autism and thimerosal-containing vaccines: lack of consistent evidence for an association.

PubMed

Stehr-Green, Paul; Tull, Peet; Stellfeld, Michael; Mortenson, Preben-Bo; Simpson, Diane

2003-08-01

In 1999, concerns were raised that vaccines containing the preservative Thimerosal might increase the risk of autism and/or other neurodevelopmental disorders. Between the mid-1980s through the late-1990s, we compared the prevalence/incidence of autism in California, Sweden, and Denmark with average exposures to Thimerosal-containing vaccines. Graphic ecologic analyses were used to examine population-based data from the United States (national immunization coverage surveys and counts of children diagnosed with autism-like disorders seeking special education services in California); Sweden (national inpatient data on autism cases, national vaccination coverage levels, and information on use of all vaccines and vaccine-specific amounts of Thimerosal); and Denmark (national registry of inpatient/outpatient-diagnosed autism cases, national vaccination coverage levels, and information on use of all vaccines and vaccine-specific amounts of Thimerosal). In all three countries, the incidence and prevalence of autism-like disorders began to rise in the 1985-1989 period, and the rate of increase accelerated in the early 1990s. However, in contrast to the situation in the United States, where the average Thimerosal dose from vaccines increased throughout the 1990s, Thimerosal exposures from vaccines in both Sweden and Denmark-already low throughout the 1970s and 1980s-began to decrease in the late 1980s and were eliminated in the early 1990s. The body of existing data, including the ecologic data presented herein, is not consistent with the hypothesis that increased exposure to Thimerosal-containing vaccines is responsible for the apparent increase in the rates of autism in young children being observed worldwide.

Universal influenza vaccines: Shifting to better vaccines.

PubMed

Berlanda Scorza, Francesco; Tsvetnitsky, Vadim; Donnelly, John J

2016-06-03

Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Real-time PCR for differential quantification of CVI988 vaccine virus and virulent strains of Marek’s disease virus

PubMed Central

Baigent, Susan J.; Nair, Venugopal K.; Le Galludec, Hervé

2016-01-01

CVI988/Rispens vaccine, the ‘gold standard’ vaccine against Marek’s disease in poultry, is not easily distinguishable from virulent strains of Marek’s disease herpesvirus (MDV). Accurate differential measurement of CVI988 and virulent MDV is commercially important to confirm successful vaccination, to diagnose Marek’s disease, and to investigate causes of vaccine failure. A real-time quantitative PCR assay to distinguish CVI988 and virulent MDV based on a consistent single nucleotide polymorphism in the pp38 gene, was developed, optimised and validated using common primers to amplify both viruses, but differential detection of PCR products using two short probes specific for either CVI988 or virulent MDV. Both probes showed perfect specificity for three commercial preparations of CVI988 and 12 virulent MDV strains. Validation against BAC-sequence-specific and US2-sequence-specific q-PCR, on spleen samples from experimental chickens co-infected with BAC-cloned pCVI988 and wild-type virulent MDV, demonstrated that CVI988 and virulent MDV could be quantified very accurately. The assay was then used to follow kinetics of replication of commercial CVI988 and virulent MDV in feather tips and blood of vaccinated and challenged experimental chickens. The assay is a great improvement in enabling accurate differential quantification of CVI988 and virulent MDV over a biologically relevant range of virus levels. PMID:26973285

Lack of Cross-protection against Bordetella holmesii after Pertussis Vaccination

PubMed Central

Zhang, Xuqing; Weyrich, Laura S.; Lavine, Jennie S.; Karanikas, Alexia T.

2012-01-01

Bordetella holmesii, a species closely related to B. pertussis, has been reported sporadically as a cause of whooping cough–like symptoms. To investigate whether B. pertussis–induced immunity is protective against infection with B. holmesii, we conducted an analysis using 11 human respiratory B. holmesii isolates collected during 2005–2009 from a highly B. pertussis–vaccinated population in Massachusetts. Neither whole-cell (wP) nor acellular (aP) B. pertussis vaccination conferred protection against these B. holmesii isolates in mice. Although T-cell responses induced by wP or aP cross-reacted with B. holmesii, vaccine-induced antibodies failed to efficiently bind B. holmesii. B. holmesii–specific antibodies provided in addition to wP were sufficient to rapidly reduce B. holmesii numbers in mouse lungs. Our findings suggest the established presence of B. holmesii in Massachusetts and that failure to induce cross-reactive antibodies may explain poor vaccine-induced cross-protection. PMID:23092514

Seasonal influenza vaccines.

PubMed

Fiore, Anthony E; Bridges, Carolyn B; Cox, Nancy J

2009-01-01

safety of LAIV among young children suggest an increased risk of wheezing in some young children, and the vaccine is not recommended for children younger than 2 years old, ages 2-4 old with a history of recurrent wheezing or reactive airways disease, or older persons who have any medical condition that confers an increased risk of influenza-related complications.The effectiveness of influenza vaccines is related predominantly to the age and immune competence of the vaccinee and the antigenic relatedness of vaccine strains to circulating strains. Vaccine effectiveness in preventing laboratory-confirmed influenza illness when the vaccine strains are well matched to circulating strains is 70-90% in randomized, placebo-controlled trials conducted among children and young healthy adults, but is lower among elderly or immunocompromised persons. In years with a suboptimal match, vaccine benefit is likely to be lower, although the vaccine can still provide substantial benefit, especially against more severe outcomes. Live, attenuated influenza vaccines have been most extensively studied among children, and have been shown to be more effective than inactivated vaccines in several randomized controlled trials among young children.Influenza vaccination is recommended in the United States for all children six months or older, all adults 50 years or older, all persons with chronic medical conditions, and pregnant women, and contacts of these persons, including healthcare workers. The global disease burden of influenza is substantial, and the World Health Organization has indicated that member states should evaluate the cost-effectiveness of introducing influenza vaccination into national immunization programs. More research is needed to develop more effective seasonal influenza vaccines that provide long-lasting immunity and broad protection against strains that differ antigenically from vaccine viruses.

Antigenic Distance Measurements for Seasonal Influenza Vaccine Selection

PubMed Central

Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

2011-01-01

Influenza vaccination is one of the major options to counteract the effects of influenza diseases. Selection of an effective vaccine strain is the key to the success of an effective vaccination program since vaccine protection can only be achieved when the selected influenza vaccine strain matches the antigenic variants causing future outbreaks. Identification of an antigenic variant is the first step to determine whether vaccine strain needs to be updated. Antigenic distance derived from immunological assays, such as hemagglutination inhibition, is commonly used to measure the antigenic closeness between circulating strains and the current influenza vaccine strain. Thus, consensus on an explicit and robust antigenic distance measurement is critical in influenza surveillance. Based on the current seasonal influenza surveillance procedure, we propose and compare three antigenic distance measurements, including Average antigenic distance (A-distance), Mutual antigenic distance (M-distance), and Largest antigenic distance (L-distance). With the assistance of influenza antigenic cartography, our simulation results demonstrated that M-distance is a robust influenza antigenic distance measurement. Experimental results on both simulation and seasonal influenza surveillance data demonstrate that M-distance can be effectively utilized in influenza vaccine strain selection. PMID:22063385