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Sample records for oral poliovirus vaccine

  1. Cessation of Trivalent Oral Poliovirus Vaccine and Introduction of Inactivated Poliovirus Vaccine - Worldwide, 2016.

    PubMed

    Hampton, Lee M; Farrell, Margaret; Ramirez-Gonzalez, Alejandro; Menning, Lisa; Shendale, Stephanie; Lewis, Ian; Rubin, Jennifer; Garon, Julie; Harris, Jennifer; Hyde, Terri; Wassilak, Steven; Patel, Manish; Nandy, Robin; Chang-Blanc, Diana

    2016-01-01

    Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, transmission of the three types of wild poliovirus (WPV) has been sharply reduced (1). WPV type 2 (WPV2) has not been detected since 1999 and was declared eradicated in September 2015. Because WPV type 3 has not been detected since November 2012, WPV type 1 (WPV1) is likely the only WPV that remains in circulation (1). This marked progress has been achieved through widespread use of oral poliovirus vaccines (OPVs), most commonly trivalent OPV (tOPV), which contains types 1, 2, and 3 live, attenuated polioviruses and has been a mainstay of efforts to prevent polio since the early 1960s. However, attenuated polioviruses in OPV can undergo genetic changes during replication, and in communities with low vaccination coverage, can result in vaccine-derived polioviruses (VDPVs) that can cause paralytic polio indistinguishable from the disease caused by WPVs (2). Among the 721 polio cases caused by circulating VDPVs (cVDPVs*) detected during January 2006-May 2016, type 2 cVDPVs (cVDPV2s) accounted for >94% (2). Eliminating the risk for polio caused by VDPVs will require stopping all OPV use. The first stage of OPV withdrawal involved a global, synchronized replacement of tOPV with bivalent OPV (bOPV) containing only types 1 and 3 attenuated polioviruses, planned for April 18-May 1, 2016, thereby withdrawing OPV type 2 from all immunization activities (3). Complementing the switch from tOPV to bOPV, introduction of at least 1 dose of injectable, trivalent inactivated poliovirus vaccine (IPV) into childhood immunization schedules reduces risks from and facilitates responses to cVDPV2 outbreaks. All 155 countries and territories that were still using OPV in immunization schedules in 2015 have reported that they had ceased use of tOPV by mid-May 2016.(†) As of August 31, 2016, 173 (89%) of 194 World Health Organization (WHO) countries included IPV in their immunization schedules.(§) The cessation of

  2. Oral and Inactivated Poliovirus Vaccines in the Newborn: A review

    PubMed Central

    Mateen, Farrah J.; Shinohara, Russell T.; Sutter, Roland W.

    2015-01-01

    Background Oral poliovirus vaccine (OPV) remains the vaccine-of-choice for routine immunization and supplemental immunization activities (SIAs) to eradicate poliomyelitis globally. Recent data from India suggested lowerthanexpected immunogenicity of an OPV birth dose, prompting a review of the immunogenicity of OPV or inactivated poliovirus vaccine (IPV) when administered at birth. Methods We evaluated the seroconversion and reported adverse events among infants given a single birth dose (given ≤7 days of life) of OPV or IPV through a systematic review of published articles and conference abstracts from 1959-2011 in any language found on PubMed, Google Scholar, or reference lists of selected articles. Results 25 articles from 13 countries published between1959 and 2011 documented seroconversion rates in newborns following an OPV dose given within the first seven days of life. There were 10 studies that measured seroconversion rates between 4 and 8 weeks of a single birth dose of TOPV, using an umbilical cord blood draw at the time of birth to establish baseline antibody levels. The percentage of newborns who seroconverted at 8 weeks range 6-42% for poliovirus type 1, 2-63% for type 2, and 1-35% for type 3). For mOPV type 1, seroconversion ranged from 10-76%; mOPV type 3, the range was 12-58%; and for the one study reporting bOPV, it was 20% for type 1 and 7% for type 3. There were four studies of IPV in newborns with a seroconversion rate of 8-100% for serotype 1, 15-100% for serotype 2, and 15-94% for serotype 3, measured at 4-6 weeks of life. No serious adverse events related to newborn OPV or IPV dosing were reported, including no cases of acute flaccid paralysis. Conclusions There is great variability of the immunogenicity of a birth dose of OPV for reasons largely unknown. Our review confirms the utility of a birth dose of OPV, particularly in countries where early induction of polio immunity is imperative. IPV has higher seroconversion rates in newborns and

  3. Current polio global eradication and control policy options: perspectives from modeling and prerequisites for oral poliovirus vaccine cessation.

    PubMed

    Thompson, Kimberly M; Tebbens, Radboud J Duintjer

    2012-04-01

    As the Global Polio Eradication Initiative progresses toward the eradication of wild polioviruses, national and global health leaders must still actively consider options for managing poliovirus risks, including risks associated with using oral poliovirus vaccine. Oral poliovirus vaccine continues to represent a highly effective tool, but its use causes noticeable, rare cases of vaccine-associated paralytic polio and with low coverage it can evolve to become circulating vaccine-derived polioviruse that causes outbreaks. National leaders face a wide range of options, but their choices depend in part on global policies. This article explores the current set of global options for poliovirus eradication or control, discusses constraints and prerequisites for their implementation and offers some insights based on dynamic modeling to inform discussions and frame future economic analyses. PMID:22551030

  4. Vaccine-derived polioviruses.

    PubMed

    Burns, Cara C; Diop, Ousmane M; Sutter, Roland W; Kew, Olen M

    2014-11-01

    The attenuated oral poliovirus vaccine (OPV) has many properties favoring its use in polio eradication: ease of administration, efficient induction of intestinal immunity, induction of durable humoral immunity, and low cost. Despite these advantages, OPV has the disadvantage of genetic instability, resulting in rare and sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) and the emergence of genetically divergent vaccine-derived polioviruses (VDPVs). Whereas VAPP is an adverse event following exposure to OPV, VDPVs are polioviruses whose genetic properties indicate prolonged replication or transmission. Three categories of VDPVs are recognized: (1) circulating VDPVs (cVDPVs) from outbreaks in settings of low OPV coverage, (2) immunodeficiency-associated VDPVs (iVDPVs) from individuals with primary immunodeficiencies, and (3) ambiguous VDPVs (aVDPVs), which cannot be definitively assigned to either of the first 2 categories. Because most VDPVs are type 2, the World Health Organization's plans call for coordinated worldwide replacement of trivalent OPV with bivalent OPV containing poliovirus types 1 and 3. PMID:25316847

  5. Analysis of mutations in oral poliovirus vaccine by hybridization with generic oligonucleotide microchips.

    SciTech Connect

    Proudnikov, D.; Kirillov, E.; Chumakov, K.; Donion, J.; Rezapkin, G.; Mirzabekov, A.; Biochip Technology Center; Engelhardt Inst. of Molecular Biology; Center for Biologics Evaluation and Research

    2000-01-01

    This paper describes use of a new technology of hybridization with a micro-array of immobilized oligonucleotides for detection and quantification of neurovirulent mutants in Oral Poliovirus Vaccine (OPV). We used a micro-array consisting of three-dimensional gel-elements containing all possible hexamers (total of 4096 probes). Hybridization of fluorescently labelled viral cDNA samples with such microchips resulted in a pattern of spots that was registered and quantified by a computer-linked CCD camera, so that the sequence of the original cDNA could be deduced. The method could reliably identify single point mutations, since each of them affected fluorescence intensity of 12 micro-array elements. Micro-array hybridization of DNA mixtures with varying contents of point mutants demonstrated that the method can detect as little as 10% of revertants in a population of vaccine virus. This new technology should be useful for quality control of live viral vaccines, as well as for other applications requiring identification and quantification of point mutations.

  6. Combined use of inactivated and oral poliovirus vaccines in refugee camps and surrounding communities - Kenya, December 2013.

    PubMed

    Sheikh, Mohamed A; Makokha, Frederick; Hussein, Abdullahi M; Mohamed, Gedi; Mach, Ondrej; Humayun, Kabir; Okiror, Samuel; Abrar, Leila; Nasibov, Orkhan; Burton, John; Unshur, Ahmed; Wannemuehler, Kathleen; Estivariz, Concepcion F

    2014-03-21

    Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, circulation of indigenous wild poliovirus (WPV) has continued without interruption in only three countries: Afghanistan, Nigeria, and Pakistan. During April-December 2013, a polio outbreak caused by WPV type 1 (WPV1) of Nigerian origin resulted in 217 cases in or near the Horn of Africa, including 194 cases in Somalia, 14 cases in Kenya, and nine cases in Ethiopia (all cases were reported as of March 10, 2014). During December 14-18, 2013, Kenya conducted the first-ever campaign providing inactivated poliovirus vaccine (IPV) together with oral poliovirus vaccine (OPV) as part of its outbreak response. The campaign targeted 126,000 children aged ≤59 months who resided in Somali refugee camps and surrounding communities near the Kenya-Somalia border, where most WPV1 cases had been reported, with the aim of increasing population immunity levels to ensure interruption of any residual WPV transmission and prevent spread from potential new importations. A campaign evaluation and vaccination coverage survey demonstrated that combined administration of IPV and OPV in a mass campaign is feasible and can achieve coverage >90%, although combined IPV and OPV campaigns come at a higher cost than OPV-only campaigns and require particular attention to vaccinator training and supervision. Future operational studies could assess the impact on population immunity and the cost-effectiveness of combined IPV and OPV campaigns to accelerate interruption of poliovirus transmission during polio outbreaks and in certain areas in which WPV circulation is endemic. PMID:24647400

  7. Influence of Enteric Infections on Response to Oral Poliovirus Vaccine: A Systematic Review and Meta-analysis

    PubMed Central

    Parker, Edward P. K.; Kampmann, Beate; Kang, Gagandeep; Grassly, Nicholas C.

    2014-01-01

    Background. The impaired immunogenicity of oral poliovirus vaccine (OPV) in low-income countries has been apparent since the early field trials of this vaccine. Infection with enteropathogens at the time of vaccination may contribute to this phenomenon. However, the relative influence of these infections on OPV performance remains uncertain. Methods. We conducted a systematic review to examine the impact of concurrent enteric infections on OPV response. Using random-effects models, we assessed the effects of nonpolio enteroviruses (NPEVs) and diarrhea on the odds of seroconversion and/or vaccine virus shedding. Results. We identified 25 trials in which OPV outcomes were compared according to the presence or absence of enteric infections, the majority of which (n = 17) reported only on NPEVs. Concurrent NPEVs significantly reduced the odds of per-dose seroconversion for type 1 poliovirus (odds ratio [OR] 0.44, 95% confidence interval 0.23−0.84), but not type 2 (OR 0.53 [0.19−1.46]) or type 3 (OR 0.56 [0.27−1.12]). A similar reduction, significant for type 1 poliovirus (OR 0.50 [0.28−0.89]), was observed in the odds of vaccine virus shedding among NPEV-infected individuals. Concurrent diarrhea significantly inhibited per-dose seroconversion overall (OR 0.61 [0.38−0.87]). Conclusions. Our findings are consistent with an inhibitory effect of concurrent enteric infections on OPV response. PMID:24688069

  8. Seroprevalence of poliovirus antibodies among 7-month-old infants after 4 doses of oral polio vaccine in Sistan-va-Baluchestan, Islamic Republic of Iran.

    PubMed

    Izadi, S; Shahmahmoodi, S; Zahraei, S M; Dorostkar, F; Majdzadeh, S-R

    2015-02-01

    Despite high coverage rates of polio vaccine in the Islamic Republic of Iran, the seroconversion rates of infants may be inadequate. This study measured seroprevalence of antibodies against poliovirus serotypes 1 to 3 (PV1, PV2 and PV3) in 7-month-old infants who had received at least 4 doses of trivalent oral polio vaccine. A serosurvey was conducted in 2010 in rural areas of Chabahar, Sistan-va-Baluchestan province. Using cluster sampling, 72 eligible infants were tested for antibody against the 3 poliovirus serotypes according to WHO guidelines. Antibody titres ≥ 1:10 were considered positive. The seropositive rates for antibody against PV1, PV2 and PV3 were 84.7%, 95.8% and 70.8% respectively. Only 63.9% of participants were seropositive for antibodies against all 3 poliovirus serotypes. Except for PV2, the seroprevalence of antibody against the other 2 poliovirus serotypes, especially PV3, was unsatisfactory. PMID:25876819

  9. Combined immunization of infants with oral and inactivated poliovirus vaccines: results of a randomized trial in The Gambia, Oman, and Thailand. WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines.

    PubMed Central

    1996-01-01

    To assess an immunization schedule combining oral (OPV) and inactivated poliovirus vaccines (IPV), we conducted a clinical trial in the Gambia, Oman, and Thailand. Children were randomized to receive one of the following schedules: OPV at birth, 6, 10, and 14 weeks of age; OPV at birth followed by both OPV and IPV at 6, 10, and 14 weeks of age: or placebo at birth followed by IPV at 6, 10, and 14 weeks of age. A total of 1685 infants were enrolled; 24-week serum specimens were available for 1291 infants (77%). Across the study sites at 24 weeks of age, the proportion of seropositive children in the combined schedule group was 95-99% for type 1, 99-100% for type 2, and 97-100% for type 3. In the Gambia and Oman, the combined schedule performed significantly better than OPV for type 1 (95-97% versus 88-90%) and type 3 (97-99% versus 72-73%). In the Gambia and Oman, seroprevalences in the IPV group were lower for type 1 (significantly lower in the Gambia); significantly lower for type 2; and significantly higher for type 3, compared with the OPV group. In Thailand, the IPV group had significantly lower proportions of children who were seropositive for each of the three types, compared with the OPV group. The responses to OPV in the Gambia, Oman, and Thailand were consistent with previous studies from these countries. IPV given at 6, 10, and 14 weeks of age provided inadequate serological protection against poliovirus, especially type 1. The combined schedule provided the highest levels of serum antibody response, with mucosal immunity equivalent to that produced by OPV alone. PMID:8789924

  10. Circulating vaccine-derived polioviruses: current state of knowledge.

    PubMed Central

    Kew, Olen M.; Wright, Peter F.; Agol, Vadim I.; Delpeyroux, Francis; Shimizu, Hiroyuki; Nathanson, Neal; Pallansch, Mark A.

    2004-01-01

    Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence. PMID:15106296

  11. Kinetics of poliovirus shedding following oral vaccination as measured by quantitative reverse transcription-PCR versus culture.

    PubMed

    Taniuchi, Mami; Begum, Sharmin; Uddin, Md Jashim; Platts-Mills, James A; Liu, Jie; Kirkpatrick, Beth D; Chowdhury, Anwarul H; Jamil, Khondoker M; Haque, Rashidul; Petri, William A; Houpt, Eric R

    2015-01-01

    Amid polio eradication efforts, detection of oral polio vaccine (OPV) virus in stool samples can provide information about rates of mucosal immunity and allow estimation of the poliovirus reservoir. We developed a multiplex one-step quantitative reverse transcription-PCR (qRT-PCR) assay for detection of OPV Sabin strains 1, 2, and 3 directly in stool samples with an external control to normalize samples for viral quantity and compared its performance with that of viral culture. We applied the assay to samples from infants in Dhaka, Bangladesh, after the administration of trivalent OPV (tOPV) at weeks 14 and 52 of life (on days 0 [pre-OPV], +4, +11, +18, and +25 relative to vaccination). When 1,350 stool samples were tested, the sensitivity and specificity of the quantitative PCR (qPCR) assay were 89 and 91% compared with culture. A quantitative relationship between culture(+)/qPCR(+) and culture(-)/qPCR(+) stool samples was observed. The kinetics of shedding revealed by qPCR and culture were similar. qPCR quantitative cutoffs based on the day +11 or +18 stool samples could be used to identify the culture-positive shedders, as well as the long-duration or high-frequency shedders. Interestingly, qPCR revealed that a small minority (7%) of infants contributed the vast majority (93 to 100%) of the total estimated viral excretion across all subtypes at each time point. This qPCR assay for OPV can simply and quantitatively detect all three Sabin strains directly in stool samples to approximate shedding both qualitatively and quantitatively. PMID:25378579

  12. Environmental Isolation of Circulating Vaccine-Derived Poliovirus After Interruption of Wild Poliovirus Transmission - Nigeria, 2016.

    PubMed

    Etsano, Andrew; Damisa, Eunice; Shuaib, Faisal; Nganda, Gatei Wa; Enemaku, Ogu; Usman, Samuel; Adeniji, Adekunle; Jorba, Jaume; Iber, Jane; Ohuabunwo, Chima; Nnadi, Chimeremma; Wiesen, Eric

    2016-01-01

    In September 2015, more than 1 year after reporting its last wild poliovirus (WPV) case in July 2014 (1), Nigeria was removed from the list of countries with endemic poliovirus transmission,* leaving Afghanistan and Pakistan as the only remaining countries with endemic WPV. However, on April 29, 2016, a laboratory-confirmed, circulating vaccine-derived poliovirus type 2 (cVDPV2) isolate was reported from an environmental sample collected in March from a sewage effluent site in Maiduguri Municipal Council, Borno State, a security-compromised area in northeastern Nigeria. VDPVs are genetic variants of the vaccine viruses with the potential to cause paralysis and can circulate in areas with low population immunity. The Nigeria National Polio Emergency Operations Center initiated emergency response activities, including administration of at least 2 doses of oral poliovirus vaccine (OPV) to all children aged <5 years through mass campaigns; retroactive searches for missed cases of acute flaccid paralysis (AFP), and enhanced environmental surveillance. Approximately 1 million children were vaccinated in the first OPV round. Thirteen previously unreported AFP cases were identified. Enhanced environmental surveillance has not resulted in detection of additional VDPV isolates. The detection of persistent circulation of VDPV2 in Borno State highlights the low population immunity, surveillance limitations, and risk for international spread of cVDPVs associated with insurgency-related insecurity. Increasing vaccination coverage with additional targeted supplemental immunization activities and reestablishment of effective routine immunization activities in newly secured and difficult-to-reach areas in Borno is urgently needed. PMID:27490081

  13. National choices related to inactivated poliovirus vaccine, innovation and the endgame of global polio eradication.

    PubMed

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J

    2014-02-01

    Achieving the goal of a world free of poliomyelitis still requires significant effort. Although polio immunization represents a mature area, the polio endgame will require new tools and strategies, particularly as national and global health leaders coordinate the cessation of all three serotypes of oral poliovirus vaccine and increasingly adopt inactivated poliovirus vaccine (IPV). Poliovirus epidemiology and the global options for managing polioviruses continue to evolve, along with our understanding and appreciation of the resources needed and the risks that require management. Based on insights from modeling, we offer some perspective on the current status of plans and opportunities to achieve and maintain a world free of wild polioviruses and to successfully implement oral poliovirus vaccine cessation. IPV costs and potential wastage will represent an important consideration for national policy makers. Innovations may reduce future IPV costs, but the world urgently needs lower-cost IPV options. PMID:24308581

  14. Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study.

    PubMed Central

    Dragunsky, Eugenia; Nomura, Tatsuji; Karpinski, Kazimir; Furesz, John; Wood, David J.; Pervikov, Yuri; Abe, Shinobu; Kurata, Takeshi; Vanloocke, Olivier; Karganova, Galina; Taffs, Rolf; Heath, Alan; Ivshina, Anna; Levenbook, Inessa

    2003-01-01

    OBJECTIVE: Extensive WHO collaborative studies were performed to evaluate the suitability of transgenic mice susceptible to poliovirus (TgPVR mice, strain 21, bred and provided by the Central Institute for Experimental Animals, Japan) as an alternative to monkeys in the neurovirulence test (NVT) of oral poliovirus vaccine (OPV). METHODS: Nine laboratories participated in the collaborative study on testing neurovirulence of 94 preparations of OPV and vaccine derivatives of all three serotypes in TgPVR21 mice. FINDINGS: Statistical analysis of the data demonstrated that the TgPVR21 mouse NVT was of comparable sensitivity and reproducibility to the conventional WHO NVT in simians. A statistical model for acceptance/rejection of OPV lots in the mouse test was developed, validated, and shown to be suitable for all three vaccine types. The assessment of the transgenic mouse NVT is based on clinical evaluation of paralysed mice. Unlike the monkey NVT, histological examination of central nervous system tissue of each mouse offered no advantage over careful and detailed clinical observation. CONCLUSIONS: Based on data from the collaborative studies the WHO Expert Committee for Biological Standardization approved the mouse NVT as an alternative to the monkey test for all three OPV types and defined a standard implementation process for laboratories that wish to use the test. This represents the first successful introduction of transgenic animals into control of biologicals. PMID:12764491

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

    PubMed

    Shimizu, Hiroyuki

    2016-04-01

    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. PMID:25448090

  16. Polio eradication. Efficacy of inactivated poliovirus vaccine in India.

    PubMed

    Jafari, Hamid; Deshpande, Jagadish M; Sutter, Roland W; Bahl, Sunil; Verma, Harish; Ahmad, Mohammad; Kunwar, Abhishek; Vishwakarma, Rakesh; Agarwal, Ashutosh; Jain, Shilpi; Estivariz, Concepcion; Sethi, Raman; Molodecky, Natalie A; Grassly, Nicholas C; Pallansch, Mark A; Chatterjee, Arani; Aylward, R Bruce

    2014-08-22

    Inactivated poliovirus vaccine (IPV) is efficacious against paralytic disease, but its effect on mucosal immunity is debated. We assessed the efficacy of IPV in boosting mucosal immunity. Participants received IPV, bivalent 1 and 3 oral poliovirus vaccine (bOPV), or no vaccine. A bOPV challenge was administered 4 weeks later, and excretion was assessed 3, 7, and 14 days later. Nine hundred and fifty-four participants completed the study. Any fecal shedding of poliovirus type 1 was 8.8, 9.1, and 13.5% in the IPV group and 14.4, 24.1, and 52.4% in the control group by 6- to 11-month, 5-year, and 10-year groups, respectively (IPV versus control: Fisher's exact test P < 0.001). IPV reduced excretion for poliovirus types 1 and 3 between 38.9 and 74.2% and 52.8 and 75.7%, respectively. Thus, IPV in OPV-vaccinated individuals boosts intestinal mucosal immunity. PMID:25146288

  17. Multiplex PCR Method for Identifying Recombinant Vaccine-Related Polioviruses

    PubMed Central

    Kilpatrick, David R.; Ching, Karen; Iber, Jane; Campagnoli, Ray; Freeman, Christopher J.; Mishrik, Nada; Liu, Hong-Mei; Pallansch, Mark A.; Kew, Olen M.

    2004-01-01

    The recent discovery of recombinant circulating vaccine-derived poliovirus (recombinant cVDPV) has highlighted the need for enhanced global poliovirus surveillance to assure timely detection of any future cVDPV outbreaks. Six pairs of Sabin strain-specific recombinant primers were designed to permit rapid screening for VDPV recombinants by PCR. PMID:15365031

  18. Fractional-Dose Inactivated Poliovirus Vaccine Immunization Campaign - Telangana State, India, June 2016.

    PubMed

    Bahl, Sunil; Verma, Harish; Bhatnagar, Pankaj; Haldar, Pradeep; Satapathy, Asish; Kumar, K N Arun; Horton, Jennifer; Estivariz, Concepcion F; Anand, Abhijeet; Sutter, Roland

    2016-01-01

    Wild poliovirus type 2 was declared eradicated in September 2015 (1). In April 2016, India, switched from use of trivalent oral poliovirus vaccine (tOPV; containing types 1, 2, and 3 polio vaccine viruses), to bivalent OPV (bOPV; containing types 1 and 3), as part of a globally synchronized initiative to withdraw Sabin poliovirus type 2 vaccine. Concurrently, inactivated poliovirus vaccine (IPV) was introduced into India's routine immunization program to maintain an immunity base that would mitigate the number of paralytic cases in the event of epidemic transmission of poliovirus type 2 (2,3). After cessation of use of type 2 Sabin vaccine, any reported isolation of vaccine-derived poliovirus type 2 (VDPV2) would be treated as a public health emergency and might need outbreak response with monovalent type 2 oral vaccine, IPV, or both (4). In response to identification of a VDPV2 isolate from a sewage sample collected in the southern state of Telangana in May 2016, India conducted a mass vaccination campaign in June 2016 using an intradermal fractional dose (0.1 ml) of IPV (fIPV). Because of a global IPV supply shortage, fIPV, which uses one fifth of regular intramuscular (IM) dose administered intradermally, has been recommended as a response strategy for VDPV2 (5). Clinical trials have demonstrated that fIPV is highly immunogenic (6,7). During the 6-day campaign, 311,064 children aged 6 weeks-3 years were vaccinated, achieving an estimated coverage of 94%. With appropriate preparation, an emergency fIPV response can be promptly and successfully implemented. Lessons learned from this campaign can be applied to successful implementation of future outbreak responses using fIPV. PMID:27559683

  19. Will containment of wild poliovirus in laboratories and inactivated poliovirus vaccine production sites be effective for global certification?

    PubMed Central

    Dowdle, Walter R.; Wolff, Christopher; Sanders, Raymond; Lambert, Scott; Best, Maureen

    2004-01-01

    The absolute laboratory containment of any virus cannot be guaranteed, but a wealth of experience indicates that effective containment of wild poliovirus materials for global certification is technically and operationally feasible. Effective containment is based on the principles of minimal wild poliovirus infectious and potentially infectious materials in laboratories; minimal risks of operations in laboratories and inactivated poliovirus vaccine production facilities; minimal susceptibility of workers to wild poliovirus infection and shedding; and minimal susceptibility of populations to wild poliovirus spread. Each principle alone is imperfect, but collectively they greatly minimize the risks of transmitting wild poliovirus from the laboratory to the community. PMID:15106302

  20. Update on Vaccine-Derived Polioviruses - Worldwide, January 2015-May 2016.

    PubMed

    Jorba, Jaume; Diop, Ousmane M; Iber, Jane; Sutter, Roland W; Wassilak, Steven G; Burns, Cara C

    2016-01-01

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide (1). One of the main tools used in polio eradication efforts has been the live, attenuated, oral poliovirus vaccine (OPV) (2), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but provides long-term protection against paralytic disease. Through effective use of OPV, the Global Polio Eradication Initiative (GPEI) has brought wild polioviruses to the threshold of eradication (1). However, OPV use, particularly in areas with low routine vaccination coverage, is associated with the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (3). VDPVs can emerge among immunologically normal vaccine recipients and their contacts as well as among persons with primary immunodeficiencies (PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in some persons with PIDs. In addition, circulating vaccine-derived polioviruses (cVDPVs) (3) can emerge in areas with low OPV coverage and can cause outbreaks of paralytic polio. This report updates previous summaries regarding VDPVs (4). PMID:27491079

  1. Examination of poliovirus vaccine preparations for SV40 sequences.

    PubMed

    Sangar, D; Pipkin, P A; Wood, D J; Minor, P D

    1999-03-01

    Oral poliovaccines derived from the strains developed by Sabin have been the basis of vaccination against poliomyelitis in the U.K. since 1962. Contamination of earlier materials with the monkey virus SV40, particularly inactivated Salk type poliovaccines, is well documented. Precautions have been in place for more than 30 years to prevent SV40 contamination of oral poliovaccines based on screening of donor animals and tests for SV40 infectivity. PCR was applied to examine all archived samples of oral poliovaccines available to us dating from 1966 to the present, including all vaccines used in the U.K. since 1980, for the presence of SV40 sequences. Of 132 materials examined, 118 were negative on initial testing and fourteen gave reactions which on further examination were attributed either to cross contamination during handling in the laboratory at National Institute for Biological Standards and Control (NIBSC) or to non-specific amplification. It was concluded that none of the samples contained SV40 sequences. The materials included 69 separate monovalent bulks of poliovirus type 1, 2 or 3 grown on monkey kidney cells from four different manufacturers and 74 bulks grown on human diploid cells from two manufacturers. One additional seed material from 1962 contained low levels of unique and characteristic SV40 sequences. The seed had been treated by the manufacturer to inactivate DNA viruses and tests by the manufacturer and at NIBSC failed to demonstrate the presence of infectious SV40 virus. Monovalent bulks prepared by the manufacturer from this seed were negative for SV40 sequences by PCR. The PCR studies provide no evidence of contamination of oral poliovaccines used in the UK with infectious SV40 and suggest that the steps taken to ensure the absence of infectious SV40 are satisfactory. PMID:10441397

  2. 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

  3. 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

  4. Update on vaccine-derived polioviruses - worldwide, July 2012-December 2013.

    PubMed

    Diop, Ousmane M; Burns, Cara C; Wassilak, Steven G; Kew, Olen M

    2014-03-21

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide. One of the main tools used in polio eradication efforts has been live, attenuated oral poliovirus vaccine (OPV), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but then it provides long-term protection against paralytic disease through durable humoral immunity. Rare cases of vaccine-associated paralytic poliomyelitis can occur among immunologically normal OPV recipients, their contacts, and persons who are immunodeficient. In addition, vaccine-derived polioviruses (VDPVs) can emerge in areas with low OPV coverage to cause polio outbreaks and can replicate for years in persons who have primary, B-cell immunodeficiencies. This report updates previous surveillance summaries and describes VDPVs detected worldwide during July 2012-December 2013. Those include a new circulating VDPV (cVDPV) outbreak identified in Pakistan in 2012, with spread to Afghanistan; an outbreak in Afghanistan previously identified in 2009 that continued into 2013; a new outbreak in Chad that spread to Cameroon, Niger, and northeastern Nigeria; and an outbreak that began in Somalia in 2008 that continued and spread to Kenya in 2013. A large outbreak in Nigeria that was identified in 2005 was nearly stopped by the end of 2013. Additionally, 10 newly identified persons in eight countries were found to excrete immunodeficiency-associated VDPVs (iVDPVs), and VDPVs were found among immunocompetent persons and environmental samples in 13 countries. Because the majority of VDPV isolates are type 2, the World Health Organization has developed a plan for coordinated worldwide replacement of trivalent OPV (tOPV) with bivalent OPV (bOPV; types 1 and 3) by 2016, preceded by introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) containing all three poliovirus serotypes into routine immunization schedules worldwide to ensure high population

  5. Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame.

    PubMed

    Pons-Salort, Margarita; Burns, Cara C; Lyons, Hil; Blake, Isobel M; Jafari, Hamid; Oberste, M Steven; Kew, Olen M; Grassly, Nicholas C

    2016-07-01

    Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55-0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity above the

  6. Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame

    PubMed Central

    Burns, Cara C.; Lyons, Hil; Blake, Isobel M.; Oberste, M. Steven; Kew, Olen M.; Grassly, Nicholas C.

    2016-01-01

    Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently “missed” groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004−2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55−0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity

  7. Notes from the Field: Circulating Vaccine-Derived Poliovirus Outbreaks - Five Countries, 2014-2015.

    PubMed

    Morales, Michelle; Nnadi, Chimeremma D; Tangermann, Rudolf H; Wassilak, Steven G F

    2016-02-12

    In 2015, wild poliovirus (WPV) transmission was identified in only Afghanistan and Pakistan (1). The widespread use of live, attenuated oral poliovirus vaccine (OPV) has been key in polio eradication efforts. However, OPV use, particularly in areas with low vaccination coverage, is associated with the low risk for emergence of vaccine-derived polioviruses (VDPV), which can cause paralysis (2). VDPVs vary genetically from vaccine viruses and can cause outbreaks in areas with low vaccination coverage. Circulating VDPVs (cVDPVs) are VDPVs in confirmed outbreaks. Single VDPVs for which the origin cannot be determined are classified as ambiguous (aVDPVs), which can also cause paralysis. Among the three types of WPV, type 2 has been declared to be eradicated. More than 90% of cVDPV cases have been caused by type 2 cVDPVs (cVDPV2). Therefore, in April 2016, all OPV-using countries of the world are discontinuing use of type 2 Sabin vaccine by simultaneously switching from trivalent OPV (types 1, 2, and 3) to bivalent OPV (types 1 and 3) for routine and supplementary immunization. The World Health Organization recently broadened the definition of cVDPVs to include any VDPV with genetic evidence of prolonged transmission (i.e., >1.5 years) and indicated that any single VDPV2 event (a case of paralysis caused by a VDPV or isolation of a VDPV from an environmental specimen) should elicit a detailed outbreak investigation and local immunization response. A confirmed cVDPV2 detection should elicit a full poliovirus outbreak response that includes multiple supplemental immunization activities (SIAs); an aVDPV designation should be made only after investigation and response (3). Since 2005, there have been 1-8 cVDPV outbreaks and 3-12 aVDPV events per year. There are currently five active cVDPV outbreaks in Guinea, Laos, Madagascar, Myanmar, and Ukraine, and four other active VDPV events. PMID:26866942

  8. Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses.

    PubMed

    Muller, David A; Pearson, Frances E; Fernando, Germain J P; Agyei-Yeboah, Christiana; Owens, Nick S; Corrie, Simon R; Crichton, Michael L; Wei, Jonathan C J; Weldon, William C; Oberste, M Steven; Young, Paul R; Kendall, Mark A F

    2016-01-01

    Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns. PMID:26911254

  9. Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

    PubMed Central

    Muller, David A.; Pearson, Frances E.; Fernando, Germain J.P.; Agyei-Yeboah, Christiana; Owens, Nick S.; Corrie, Simon R.; Crichton, Michael L.; Wei, Jonathan C.J.; Weldon, William C.; Oberste, M. Steven; Young, Paul R.; Kendall, Mark A. F.

    2016-01-01

    Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns. PMID:26911254

  10. Interim CDC guidance for polio vaccination for travel to and from countries affected by wild poliovirus.

    PubMed

    Wallace, Gregory S; Seward, Jane F; Pallansch, Mark A

    2014-07-11

    In the prevaccine era, infection with wild poliovirus (WPV) was common worldwide, with seasonal peaks and epidemics in the summer and fall in temperate areas. The incidence of poliomyelitis in the United States declined rapidly after the licensure of inactivated polio vaccine (IPV) in 1955 and live oral polio vaccine (OPV) in the 1960s. The last cases of indigenously acquired WPV in the United States occurred in 1979, the last WPV case in a U.S. resident traveling abroad occurred in 1986, and the last WPV imported case was in 1993. Since 2000, the United States has exclusively used IPV, resulting in prevention of 8-10 vaccine-associated paralytic poliomyelitis cases annually. In 2005, an unvaccinated U.S. adult traveling abroad acquired vaccine-associated paralytic poliomyelitis after contact with an infant recently vaccinated with OPV. PMID:25006826

  11. PER.C6(®) cells as a serum-free suspension cell platform for the production of high titer poliovirus: a potential low cost of goods option for world supply of inactivated poliovirus vaccine.

    PubMed

    Sanders, Barbara P; Edo-Matas, Diana; Custers, Jerome H H V; Koldijk, Martin H; Klaren, Vincent; Turk, Marije; Luitjens, Alfred; Bakker, Wilfried A M; Uytdehaag, Fons; Goudsmit, Jaap; Lewis, John A; Schuitemaker, Hanneke

    2013-01-21

    There are two highly efficacious poliovirus vaccines: Sabin's live-attenuated oral polio vaccine (OPV) and Salk's inactivated polio vaccine (IPV). OPV can be made at low costs per dose and is easily administrated. However, the major drawback is the frequent reversion of the OPV vaccine strains to virulent poliovirus strains which can result in Vaccine Associated Paralytic Poliomyelitis (VAPP) in vaccinees. Furthermore, some OPV revertants with high transmissibility can circulate in the population as circulating Vaccine Derived Polioviruses (cVDPVs). IPV does not convey VAPP and cVDPVs but the high costs per dose and insufficient supply have rendered IPV an unfavorable option for low and middle-income countries. Here, we explored whether the human PER.C6(®) cell-line, which has the unique capability to grow at high density in suspension, under serum-free conditions, could be used as a platform for high yield production of poliovirus. PER.C6(®) cells supported replication of all three poliovirus serotypes with virus titers ranging from 9.4 log(10) to 11.1 log(10)TCID(50)/ml irrespective of the volume scale (10 ml in shaker flasks to 2 L in bioreactors). This production yield was 10-30 fold higher than in Vero cell cultures performed here, and even 100-fold higher than what has been reported for Vero cell cultures in literature [38]. In agreement, the D-antigen content per volume PER.C6(®)-derived poliovirus was on average 30-fold higher than Vero-derived poliovirus. Interestingly, PER.C6(®) cells produced on average 2.5-fold more D-antigen units per cell than Vero cells. Based on our findings, we are exploring PER.C6(®) as an interesting platform for large-scale production of poliovirus at low costs, potentially providing the basis for global supply of an affordable IPV. PMID:23123018

  12. Multiple Independent Emergences of Type 2 Vaccine-Derived Polioviruses during a Large Outbreak in Northern Nigeria

    PubMed Central

    Shaw, Jing; Jorba, Jaume; Bukbuk, David; Adu, Festus; Gumede, Nicksy; Pate, Muhammed Ali; Abanida, Emmanuel Ade; Gasasira, Alex; Iber, Jane; Chen, Qi; Vincent, Annelet; Chenoweth, Paul; Henderson, Elizabeth; Wannemuehler, Kathleen; Naeem, Asif; Umami, Rifqiyah Nur; Nishimura, Yorihiro; Shimizu, Hiroyuki; Baba, Marycelin; Adeniji, Adekunle; Williams, A. J.; Kilpatrick, David R.; Oberste, M. Steven; Wassilak, Steven G.; Tomori, Oyewale; Pallansch, Mark A.; Kew, Olen

    2013-01-01

    Since 2005, a large poliomyelitis outbreak associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) has occurred in northern Nigeria, where immunization coverage with trivalent oral poliovirus vaccine (tOPV) has been low. Phylogenetic analysis of P1/capsid region sequences of isolates from each of the 403 cases reported in 2005 to 2011 resolved the outbreak into 23 independent type 2 vaccine-derived poliovirus (VDPV2) emergences, at least 7 of which established circulating lineage groups. Virus from one emergence (lineage group 2005-8; 361 isolates) was estimated to have circulated for over 6 years. The population of the major cVDPV2 lineage group expanded rapidly in early 2009, fell sharply after two tOPV rounds in mid-2009, and gradually expanded again through 2011. The two major determinants of attenuation of the Sabin 2 oral poliovirus vaccine strain (A481 in the 5′-untranslated region [5′-UTR] and VP1-Ile143) had been replaced in all VDPV2 isolates; most A481 5′-UTR replacements occurred by recombination with other enteroviruses. cVDPV2 isolates representing different lineage groups had biological properties indistinguishable from those of wild polioviruses, including efficient growth in neuron-derived HEK293 cells, the capacity to cause paralytic disease in both humans and PVR-Tg21 transgenic mice, loss of the temperature-sensitive phenotype, and the capacity for sustained person-to-person transmission. We estimate from the poliomyelitis case count and the paralytic case-to-infection ratio for type 2 wild poliovirus infections that ∼700,000 cVDPV2 infections have occurred during the outbreak. The detection of multiple concurrent cVDPV2 outbreaks in northern Nigeria highlights the risks of cVDPV emergence accompanying tOPV use at low rates of coverage in developing countries. PMID:23408630

  13. The Sabin live poliovirus vaccination trials in the USSR, 1959.

    PubMed Central

    Horstmann, D. M.

    1991-01-01

    Widespread use of the Sabin live attenuated poliovirus vaccine has had tremendous impact on the disease worldwide, virtually eliminating it from a number of countries, including the United States. Early proof of its safety and effectiveness was presented in 1959 by Russian investigators, who had staged massive trials in the USSR, involving millions of children. Their positive results were at first viewed in the United States and elsewhere with some skepticism, but the World Health Organization favored proceeding with large-scale trials, and responded to the claims made by Russian scientists by sending a representative to the USSR to review in detail the design and execution of the vaccine programs and the reliability of their results. The report that followed was a positive endorsement of the findings and contributed to the acceptance of the Sabin vaccine in the United States, where it has been the polio vaccine of choice since the mid-1960s. PMID:1814062

  14. Sabin Vaccine Reversion in the Field: a Comprehensive Analysis of Sabin-Like Poliovirus Isolates in Nigeria

    PubMed Central

    Chang, Stewart; Iber, Jane; Zhao, Kun; Adeniji, Johnson A.; Bukbuk, David; Baba, Marycelin; Behrend, Matthew; Burns, Cara C.; Oberste, M. Steven

    2015-01-01

    ABSTRACT To assess the dynamics of genetic reversion of live poliovirus vaccine in humans, we studied molecular evolution in Sabin-like poliovirus isolates from Nigerian acute flaccid paralysis cases obtained from routine surveillance. We employed a novel modeling approach to infer substitution and recombination rates from whole-genome sequences and information about poliovirus infection dynamics and the individual vaccination history. We confirmed observations from a recent vaccine trial that VP1 substitution rates are increased for Sabin-like isolates relative to the rate for the wild type due to increased nonsynonymous substitution rates. We also inferred substitution rates for attenuating nucleotides and confirmed that reversion can occur in days to weeks after vaccination. We combine our observations for Sabin-like virus evolution with the molecular clock for VP1 of circulating wild-type strains to infer that the mean time from the initiating vaccine dose to the earliest detection of circulating vaccine-derived poliovirus (cVDPV) is 300 days for Sabin-like virus type 1, 210 days for Sabin-like virus type 2, and 390 days for Sabin-like virus type 3. Phylogenetic relationships indicated transient local transmission of Sabin-like virus type 3 and, possibly, Sabin-like virus type 1 during periods of low wild polio incidence. Comparison of Sabin-like virus recombinants with known Nigerian vaccine-derived poliovirus recombinants shows that while recombination with non-Sabin enteroviruses is associated with cVDPV, the recombination rates are similar for Sabin isolate-Sabin isolate and Sabin isolate–non-Sabin enterovirus recombination after accounting for the time from dosing to the time of detection. Our study provides a comprehensive picture of the evolutionary dynamics of the oral polio vaccine in the field. IMPORTANCE The global polio eradication effort has completed its 26th year. Despite success in eliminating wild poliovirus from most of the world, polio

  15. High resolution identity testing of inactivated poliovirus vaccines

    PubMed Central

    Mee, Edward T.; Minor, Philip D.; Martin, Javier

    2015-01-01

    Background Definitive identification of poliovirus strains in vaccines is essential for quality control, particularly where multiple wild-type and Sabin strains are produced in the same facility. Sequence-based identification provides the ultimate in identity testing and would offer several advantages over serological methods. Methods We employed random RT-PCR and high throughput sequencing to recover full-length genome sequences from monovalent and trivalent poliovirus vaccine products at various stages of the manufacturing process. Results All expected strains were detected in previously characterised products and the method permitted identification of strains comprising as little as 0.1% of sequence reads. Highly similar Mahoney and Sabin 1 strains were readily discriminated on the basis of specific variant positions. Analysis of a product known to contain incorrect strains demonstrated that the method correctly identified the contaminants. Conclusion Random RT-PCR and shotgun sequencing provided high resolution identification of vaccine components. In addition to the recovery of full-length genome sequences, the method could also be easily adapted to the characterisation of minor variant frequencies and distinction of closely related products on the basis of distinguishing consensus and low frequency polymorphisms. PMID:26049003

  16. An Introduction to Poliovirus: Pathogenesis, Vaccination, and the Endgame for Global Eradication.

    PubMed

    Minor, Philip D

    2016-01-01

    Poliomyelitis is caused by poliovirus, which is a positive strand non-enveloped virus that occurs in three distinct serotypes (1, 2, and 3). Infection is mainly by the fecal-oral route and can be confined to the gut by antibodies induced either by vaccine, previous infection or maternally acquired. Vaccines include the live attenuated strains developed by Sabin and the inactivated vaccines developed by Salk; the live attenuated vaccine (Oral Polio Vaccine or OPV) has been the main tool in the Global Program of Polio eradication of the World Health Organisation. Wild type 2 virus has not caused a case since 1999 and type 3 since 2012 and eradication seems near. However most infections are entirely silent so that sophisticated environmental surveillance may be needed to ensure that the virus has been eradicated, and the live vaccine can sometimes revert to virulent circulating forms under conditions that are not wholly understood. Cessation of vaccination is therefore an increasingly important issue and inactivated polio vaccine (IPV) is playing a larger part in the end game. PMID:26983727

  17. Update on Vaccine-Derived Polioviruses - Worldwide, January 2014-March 2015.

    PubMed

    Diop, Ousmane M; Burns, Cara C; Sutter, Roland W; Wassilak, Steven G; Kew, Olen M

    2015-06-19

    Since the World Health Assembly's 1988 resolution to eradicate poliomyelitis, one of the main tools of the World Health Organization (WHO) Global Polio Eradication Initiative (GPEI) has been the live, attenuated oral poliovirus vaccine (OPV). OPV might require several doses to induce immunity but provides long-term protection against paralytic disease. Through effective use of OPV, GPEI has brought polio to the threshold of eradication. Wild poliovirus type 2 (WPV2) was eliminated in 1999, WPV3 has not been detected since November 2012, and WPV1 circulation appears to be restricted to parts of Pakistan and Afghanistan. However, continued use of OPV carries two key risks. The first, vaccine-associated paralytic poliomyelitis (VAPP) has been recognized since the early 1960s. VAPP is a very rare event that occurs sporadically when an administered dose of OPV reverts to neurovirulence and causes paralysis in the vaccine recipient or a nonimmune contact. VAPP can occur among immunologically normal vaccine recipients and their contacts as well as among persons who have primary immunodeficiencies (PIDs) manifested by defects in antibody production; it is not associated with outbreaks. The second, the emergence of genetically divergent, neurovirulent vaccine-derived polioviruses (VDPVs) was recognized more recently. Circulating VDPVs (cVDPVs) resemble WPVs and, in areas with low OPV coverage, can cause polio outbreaks. Immunodeficiency-associated VDPVs (iVDPVs) can replicate and be excreted for years in some persons with PIDs; GPEI maintains a registry of iVDPV cases. Ambiguous VDPVs (aVDPVs) are isolates that cannot be classified definitively. This report updates previous surveillance summaries and describes VDPVs detected worldwide during January 2014-March 2015. Those include new cVDPV outbreaks in Madagascar and South Sudan, and sharply reduced type 2 cVDPV (cVDPV2) circulation in Nigeria and Pakistan during the latter half of 2014. Eight newly identified persons in

  18. Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.

    PubMed

    Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V

    2015-10-13

    Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. PMID:26362098

  19. [Circulating vaccine-derived poliovirus type 2 outbreak in Democratic Republic of Congo 2011-2012].

    PubMed

    Bazira, L; Coulibaly, T; Mayenga, M; Ncharre, C; Yogolelo, R; Mbule, A; Moudzeo, H; Lwamba, P; Mulumba, A W; Cabore, J

    2015-10-01

    According to the WHO records of 2013, the incidence of poliomyelitis was reduced by more than 99%, the number of endemic countries decreased from 125 in 1988 to 3 in 2013 and over 10 million cases were prevented from poliomyelitis thanks to the intensive use of Oral polio vaccine (OPV). However, the emergence of circulating vaccine-derived poliovirus strains (cVDPV), causing serious epidemics like the wild poliovirus, is a major challenge on the final straight towards the goal of eradication and OPV cessation. This paper describes the cVDPVoutbreak that occurred in the Democratic Republic of Congo (DRC) from November 2011 to April 2012. All children under 15 years of age with acute flaccid paralysis (AFP) and confirmed presence of cVDPV in the stool samples were included. Thirty (30) children, all from the administrative territories of Bukama and Malemba Nkulu in the Katanga Province (south-east DRC), were reported. The virus responsible was the cVDPV type 2 (0.7% -3.5% divergent from the reference Sabin 2 strain) in 29 children (97%) and the ambiguous vaccine-derived poliovirus strain (0.7% divergent) was confirmed in one case (3%), a boy seventeen months old and already vaccinated four times with OPV. Twentyfive children (83%) were protected by any of the routine EPI vaccines and 3 children (10%) had never received any dose of OPV. In reaction, DRC has conducted five local campaigns over a period of 10 months (from January to October 2012) and the epidemic was stopped after the second round performed in March 2012. As elsewhere in similar conditions, low immunization coverage, poor sanitation conditions and the stop of the use of OPV2 have favoured the emergence of the third cVDPV epidemic in DRC. The implementation of the Strategic Plan for Polio eradication and endgame strategic plan 2013-2018 will prevent the emergence of cVDPV and set up the conditions for a coordinated OPV phase out. PMID:26288132

  20. Assessment of attitudes towards adverse events following immunization with oral poliovirus vaccine: a pilot study among high school students of Kinshasa, the Democratic Republic of Congo

    PubMed Central

    Kinuani, Léon; Nzolo, Didier Bomene; Aloni, Michel Ntetani; Makolo, Pavel; Ntamabyaliro, Nsengi; Ntamba, Yves Lula; Kazadi, Crispin; Nyembwe, Michel; Ekila, Mathilde Bothale; Mesia, Gauthier Kahunu

    2014-01-01

    Objective: The aim of this study is to evaluate the reaction of students to adverse events following immunization in order to offer a baseline for developing a communication and risk management plan. Method: This is a cross-sectional study conducted in Kinshasa. A survey was conducted between the third and the fourth rounds of Supplementary Immunization Activity. Nine hundred and fifty questionnaires were used and addressed students who attended this university from 1 to 10 June 2011. Results: Completed questionnaires were received from 848 students, with 485 females (57.2%), 343 males (40.4%), and 20 unknown (2.4%); 46.9% of students were from the faculty of medicine and 24.7% was from the third graduate degree. From those who completed the questionnaire, 136 (16.4%) reported experiencing an adverse events following immunization. Concerning the attitude of students towards adverse events following immunization, 79 students (58.5%) did nothing; 54 (40.0%) opted for self-medication; 2 (1.5%) went to the hospital. Conclusion: The main finding of our study is the low rate of people referring to health-care providers for vaccine-related problems, more specially for adverse events following immunization. A risk management plan should be focused in strategies to increase communication between population and health-care providers. PMID:25237792

  1. Limited and localized outbreak of newly emergent type 2 vaccine-derived poliovirus in Sichuan, China.

    PubMed

    Yan, Dongmei; Zhang, Yong; Zhu, Shuangli; Chen, Na; Li, Xiaolei; Wang, Dongyan; Ma, Xiaozhen; Zhu, Hui; Tong, Wenbin; Xu, Wenbo

    2014-07-01

    From August 2011 to February 2012, an outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV) occurred in Aba County, Sichuan, China. During the outbreak, four type 2 VDPVs (≥0.6% nucleotide divergence in the VP1 region relative to the Sabin 2 strain) were isolated from 3 patients with acute flaccid paralysis (AFP) and one close contact. In addition, a type 2 pre-VDPV (0.3% to 0.5% divergence from Sabin 2) that was genetically related to these type 2 VDPVs was isolated from another AFP patient. These 4 patients were all unimmunized children 0.7 to 1.1 years old. Nucleotide sequencing revealed that the 4 VDPV isolates differed from Sabin 2 by 0.7% to 1.2% in nucleotides in the VP1 region and shared 5 nucleotide substitutions with the pre-VDPV. All 5 isolates were closely related, and all were S2/S3/S2/S3 recombinants sharing common recombination crossover sites. Although the two major determinants of attenuation and temperature sensitivity phenotype of Sabin 2 (A481 in the 5' untranslated region and Ile143 in the VP1 protein) had reverted in all 5 isolates, one VDPV (strain CHN16017) still retained the temperature sensitivity phenotype. Phylogenetic analysis of the third coding position of the complete P1 coding region suggested that the cVDPVs circulated locally for about 7 months following the initiating oral poliovirus vaccine (OPV) dose. Our findings reinforce the point that cVDPVs can emerge and spread in isolated communities with immunity gaps and highlight the emergence risks of type 2 cVDPVs accompanying the trivalent OPV used. To solve this issue, it is recommended that type 2 OPV be removed from the trivalent OPV or that inactivated polio vaccine (IPV) be used instead. PMID:24850620

  2. Immune response to simultaneous administration of a combined measles, mumps and rubella vaccine with booster doses of diphtheria-tetanus and poliovirus vaccine.

    PubMed

    Giammanco, G; Li Volti, S; Salemi, I; Giammanco Bilancia, G; Mauro, L

    1993-03-01

    A combined vaccine against measles (Edmonston-Zagreb 19 strain), mumps (Rubini strain) and rubella (Wistar RA 27/3 strain) was administered to a group of 46 children aged 10-12 months simultaneously with booster doses of compulsory diphtheria-tetanus toxoid and oral poliovirus vaccine. A second group of 53 children aged 15-24 months who had received booster doses of the compulsory vaccines 5 to 12 months before was also vaccinated. The same seroconversion rates (100%) and similar antibody titers for rubella were observed in both groups. The same seroconversion rates for mumps (93%) and similar rates for measles (98 and 94%) were observed in the two groups. Significantly lower antibody titers for measles and mumps were found in the first group, but they were compensated by an earlier protection, a reduction of number of visits for immunization, costs for the community, and improvement in parental compliance. These results confirm that Edmonston-Zagreb 19 and Rubini strains are still immunogenic even when they are combined with Wistar RA 27/3 strain. Moreover, a long term follow-up in order to verify the persistence of protective antibody levels in both groups of children, could suggest that combined measles, mumps and rubella vaccine could be given earlier (at 10-12 months of age), simultaneously with booster doses of diphtheria and tetanus toxoid and of trivalent oral poliovirus vaccine. PMID:8519358

  3. Development of a multiplex RT-PCR assay for the identification of recombination types at different genomic regions of vaccine-derived polioviruses.

    PubMed

    Dimitriou, T G; Kyriakopoulou, Z; Tsakogiannis, D; Fikatas, A; Gartzonika, C; Levidiotou-Stefanou, S; Markoulatos, P

    2016-08-01

    Polioviruses (PVs) are the causal agents of acute paralytic poliomyelitis. Since the 1960s, poliomyelitis has been effectively controlled by the use of two vaccines containing all three serotypes of PVs, the inactivated poliovirus vaccine and the live attenuated oral poliovirus vaccine (OPV). Despite the success of OPV in polio eradication programme, a significant disadvantage was revealed: the emergence of vaccine-associated paralytic poliomyelitis (VAPP). VAPP is the result of accumulated mutations and putative recombination events located at the genome of attenuated vaccine Sabin strains. In the present study, ten Sabin isolates derived from OPV vaccinees and environmental samples were studied in order to identify recombination types located from VP1 to 3D genomic regions of virus genome. The experimental procedure that was followed was virus RNA extraction, reverse transcription to convert the virus genome into cDNA, PCR and multiplex-PCR using specific designed primers able to localize and identify each recombination following agarose gel electrophoresis. This multiplex RT-PCR assay allows for the immediate detection and identification of multiple recombination types located at the viral genome of OPV derivatives. After the eradication of wild PVs, the remaining sources of poliovirus infection worldwide would be the OPV derivatives. As a consequence, the immediate detection and molecular characterization of recombinant derivatives are important to avoid epidemics due to the circulation of neurovirulent viral strains. PMID:27098645

  4. New Generation of Inactivated Poliovirus Vaccines for Universal Immunization After Eradication of Poliomyelitis

    PubMed Central

    Chumakov, Konstantin; Ehrenfeld, Ellie

    2008-01-01

    Twenty years of global polio eradication efforts may soon eliminate wild-type poliovirus transmission. However, new information about poliovirus learned during this campaign, as well as the political realities of a modern world demand that universal immunity against poliomyelitis be maintained even after wild poliovirus is eradicated. Although two excellent vaccines have proven highly effective in the past, neither the live nor current inactivated products are optimal for use in the post-eradication setting. Therefore, concerted efforts are urgently needed to develop a new generation of vaccine that is risk-free and affordable and can be produced on a global scale. Here we discuss the desired properties and ways to create a new polio vaccine. PMID:18990066

  5. Immunogenicity of poliovirus vaccines in chronically malnourished infants: A randomized controlled trial in Pakistan

    PubMed Central

    Saleem, Ali Faisal; Mach, Ondrej; Quadri, Farheen; Khan, Asia; Bhatti, Zaid; Rehman, Najeeb ur; Zaidi, Sohail; Weldon, William C.; Oberste, Steven M.; Salama, Maha; Sutter, Roland W.; Zaidi, Anita K.M.

    2015-01-01

    Reaching high population immunity against polioviruses (PV) is essential to achieving global polio eradication. Efficacy of oral poliovirus vaccine (OPV) varies and is lower among children living in tropical areas with impoverished environments. Malnutrition found as a risk factor for lower serological protection against PV. We compared whether inactivated polio vaccine (IPV) can be used to rapidly close the immunity gap among chronically malnourished (stunted) infants in Pakistan who will not be eligible for the 14 week IPV dose in routine EPI schedule. A phase 3, multicenter 4-arm randomized controlled trial conducted at five Primary Health Care (PHC) centers in Karachi, Pakistan. Infants, 9–12 months were stratified by length for age Z score into chronically malnourished and normally nourished. Infants were randomized to receive one dose of either bivalent OPV (bOPV) alone or bOPV + IPV. Baseline seroprevalence of PV antibodies and serum immune response to study vaccine dose were assessed by neutralization assay. Vaccine PV shedding in stool was evaluated 7 days after a bOPV challenge dose. Sera and stool were analyzed from 852/928 (92%) enrolled children. At baseline, the seroprevalence was 85.6% (n = 386), 73.6% (n = 332), and 70.7% (n = 319) in malnourished children against PV types 1, 2 and 3 respectively; and 94.1% (n = 448), 87.0% (n = 441) and 83.6% (n = 397) in the normally nourished group (p < 0.05). Children had previously received 9–10 doses of bOPV (80%) or tOPV (20%). One dose of IPV + bOPV given to malnourished children increased their serological protection (PV1, n = 201, 97.6%; PV2, n = 198, 96.1% and PV3, n = 189, 91.7%) to parity with normally nourished children who had not received IPV (p = <0.001). Seroconversion and boosting for all three serotypes was significantly more frequent in children who received IPV + bOPV than in those with bOPV only (p < 0.001) in both strata. Shedding of polioviruses in stool did

  6. Failure to detect infection by oral polio vaccine virus following natural exposure among inactivated polio vaccine recipients

    PubMed Central

    GARY, H. E.; SMITH, B.; JENKS, J.; RUIZ, J.; SESSIONS, W.; VINJE, J.; SOBSEY, M.

    2008-01-01

    SUMMARY While oral polio vaccine (OPV) has been shown to be safe and effective, it has been observed that it can circulate within a susceptible population and revert to a virulent form. Inactivated polio vaccine (IPV) confers protection from paralytic disease, but provides limited protection against infection. It is possible, then, that an IPV-immunized population, when exposed to OPV, could sustain undetected circulation of vaccine-derived poliovirus. This study examines the possibility of polio vaccine virus circulating within the United States (highly IPV-immunized) population that borders Mexico (OPV-immunized). A total of 653 stool and 20 sewage samples collected on the US side of the border were tested for the presence of poliovirus. All samples were found to be negative. These results suggest that the risk of circulating vaccine-derived poliovirus is low in fully immunized IPV-using populations in developed countries that border OPV-using populations. PMID:17376256

  7. Viral Aetiology of Acute Flaccid Paralysis Surveillance Cases, before and after Vaccine Policy Change from Oral Polio Vaccine to Inactivated Polio Vaccine

    PubMed Central

    Saraswathy Subramaniam, T. S.; Apandi, Mohd Apandi; Jahis, Rohani; Samsudin, Mohd Samsul; Saat, Zainah

    2014-01-01

    Since 1992, surveillance for acute flaccid paralysis (AFP) cases was introduced in Malaysia along with the establishment of the National Poliovirus Laboratory at the Institute for Medical Research. In 2008, the Ministry of Health, Malaysia, approved a vaccine policy change from oral polio vaccine to inactivated polio vaccine (IPV). Eight states started using IPV in the Expanded Immunization Programme, followed by the remaining states in January 2010. The objective of this study was to determine the viral aetiology of AFP cases below 15 years of age, before and after vaccine policy change from oral polio vaccine to inactivated polio vaccine. One hundred and seventy-nine enteroviruses were isolated from the 3394 stool specimens investigated between 1992 and December 2012. Fifty-six out of 107 virus isolates were polioviruses and the remaining were non-polio enteroviruses. Since 2009 after the sequential introduction of IPV in the childhood immunization programme, no Sabin polioviruses were isolated from AFP cases. In 2012, the laboratory AFP surveillance was supplemented with environmental surveillance with sewage sampling. Thirteen Sabin polioviruses were also isolated from sewage in the same year, but no vaccine-derived poliovirus was detected during this period. PMID:24772175

  8. Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

    NASA Technical Reports Server (NTRS)

    Butel, J. S.

    2000-01-01

    From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

  9. Effects of hydrostatic pressure on the stability and thermostability of poliovirus: a new method for vaccine preservation.

    PubMed

    Ferreira, Evanilce; Mendes, Ygara S; Silva, Jerson L; Galler, Ricardo; Oliveira, Andréa C; Freire, Marcos S; Gaspar, Luciane P

    2009-08-27

    Viruses are a structurally diverse group of infectious agents that differ widely in their sensitivities to high hydrostatic pressure (HHP). Studies on picornaviruses have demonstrated that these viruses are extremely resistant to HHP treatments, with poliovirus appearing to be the most resistant. Here, the three attenuated poliovirus serotypes were compared with regard to pressure and thermal resistance. We found that HHP does not inactivate any of the three serotypes studied (1-3). Rather, HHP treatment was found to stabilize poliovirus by increasing viral thermal resistance at 37 degrees C. Identification of new methods that stabilize poliovirus against heat inactivation would aid in the design of a more heat-stable vaccine, circumventing the problems associated with refrigeration during storage and transport of the vaccine prior to use. PMID:19616496

  10. The compatibility of inactivated-Enterovirus 71 vaccination with Coxsackievirus A16 and Poliovirus immunizations in humans and animals

    PubMed Central

    Mao, Qunying; Wang, Yiping; Shao, Jie; Ying, Zhifang; Gao, Fan; Yao, Xin; Li, Changgui; Ye, Qiang; Xu, Miao; Li, Rongcheng; Zhu, Fengcai; Liang, Zhenglun

    2015-01-01

    Enterovirus 71 (EV71) is the key pathogen for Hand, Foot, and Mouth Disease (HFMD) and can result in severe neurological complications and death among young children. Three inactivated-EV71 vaccines have gone through phase III clinical trials and have demonstrated good safety and efficacy. These vaccines will benefit young children under the threat of severe HFMD. However, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to include the EV71 vaccine in Expanded Program on Immunization (EPI). Here, we measured the neutralizing antibodies (NTAbs) against EV71, Coxsackievirus A16 (CA16) and Poliovirus from infants enrolled in those EV71 vaccine clinical trials. The results indicated that the levels of NTAb GMTs for EV71 increased significantly in all 3 vaccine groups (high, middle and low dosages, respectively) post-vaccination. Seroconversion ratios and Geometric mean fold increase were significantly higher in the vaccine groups (≥7/9 and 8.9~228.1) than in the placebo group (≤1/10 and 0.8~1.7, P < 0.05). But no similar NTAb response trends were found in CA16 and 3 types of Poliovirus. The decrease of 3 types of Poliovirus NTAb GMTs and an increase of CA16 GMTs post-EV71-vaccination were found in vaccine and placebo groups. Further animal study on CA16 and poliovirus vaccine co-immunization or pre-immunization with EV71 vaccine in mice indicated that there was no NTAb cross-activity between EV71 and CA16/Poliovirus. Our research showed that inactivated-EV71 vaccine has good specific-neutralizing capacity and can be included in EPI. PMID:25715318

  11. Modeling population immunity to support efforts to end the transmission of live polioviruses.

    PubMed

    Thompson, Kimberly M; Pallansch, Mark A; Tebbens, Radboud J Duintjer; Wassilak, Steve G; Cochi, Stephen L

    2013-04-01

    Eradication of wild poliovirus (WPV) types 1 and 3, prevention and cessation of circulating vaccine-derived polioviruses, and achievement and maintenance of a world free of paralytic polio cases requires active risk management by focusing on population immunity and coordinated cessation of oral poliovirus vaccine (OPV). We suggest the need for a complementary and different conceptual approach to achieve eradication compared to the current case-based approach using surveillance for acute flaccid paralysis (AFP) to identify symptomatic poliovirus infections. Specifically, we describe a modeling approach to characterize overall population immunity to poliovirus transmission. The approach deals with the realities that exposure to live polioviruses (e.g., WPV, OPV) and/or vaccination with inactivated poliovirus vaccine provides protection from paralytic polio (i.e., disease), but does not eliminate the potential for reinfection or asymptomatic participation in poliovirus transmission, which may increase with time because of waning immunity. The AFP surveillance system provides evidence of symptomatic poliovirus infections detected, which indicate immunity gaps after outbreaks occur, and this system represents an appropriate focus for controlling disease outbreaks. We describe a conceptual dynamic model to characterize population immunity to poliovirus transmission that helps identify risks created by immunity gaps before outbreaks occur, which provides an opportunity for national and global policymakers to manage the risk of poliovirus and prevent outbreaks before they occur. We suggest that dynamically modeling risk represents an essential tool as the number of cases approaches zero. PMID:22985171

  12. An Outbreak of Type Π Vaccine-Derived Poliovirus in Sichuan Province, China: Emergence and Circulation in an Under-Immunized Population

    PubMed Central

    Fan, Chun-Xiang; Liu, Qing-Lian; Hao, Li-Xin; Liu, Yu; Zheng, Jing-Shan; Qin, Zhi-Ying; Xia, Wei; Zhang, Shi-Yue; Yin, Zun-Dong; Jing, Qiong; Zhang, Yan-Xia; Huang, Rong-Na; Yang, Ru-Pei; Tong, Wen-Bin; Qi, Qi; Guan, Xu-Jing; Jing, Yu-Lin; Ma, Qian-Li; Wang, Jin; Ma, Xiao-Zhen; Chen, Na; Zheng, Hong-Ru; Li, Yin-Qiao; Ma, Chao; Su, Qi-Ru; Reilly, Kathleen H.; Luo, Hui-Ming; Wu, Xian-Ping; Wen, Ning; Yang, Wei-Zhong

    2014-01-01

    Background During August 2011–February 2012, an outbreak of type Π circulating vaccine-derived poliovirus (cVDPVs) occurred in Sichuan Province, China. Methods A field investigation of the outbreak was conducted to characterize outbreak isolates and to guide emergency response. Sequence analysis of poliovirus capsid protein VP1 was performed to determine the viral propagation, and a coverage survey was carried out for risk assessment. Results One clinical compatible polio case and three VDPV cases were determined in Ngawa County, Ngawa Tibetan and Qiang Autonomous Prefecture, Sichuan Province. Case patients were unimmunized children, 0.8–1 years old. Genetic sequencing showed that the isolates diverged from the VP1 region of the type Π Sabin strain by 5–12 nucleotides (nt) and shared the same 5 nt VP1 substitutions, which indicate single lineage of cVDPVs. Of the 7 acute flaccid paralysis cases (all>6 months) reported in Ngawa Prefecture in 2011, 4 (57.1%) cases (including 2 polio cases) did not receive oral attenuated poliovirus vaccine. Supplementary immunization activities (SIAs) were conducted in February–May, 2012, and the strain has not been isolated since. Conclusion High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Risk assessments should be conducted regularly to pinpoint high risk areas or subpopulations, with SIAs developed if necessary. PMID:25503964

  13. Immunogenicity and Effectiveness of Routine Immunization With 1 or 2 Doses of Inactivated Poliovirus Vaccine: Systematic Review and Meta-analysis

    PubMed Central

    Grassly, Nicholas C.

    2014-01-01

    Background. The World Health Organization has recommended that all 124 countries currently using only oral poliovirus vaccine (OPV) introduce at least 1 dose of inactivated poliovirus vaccine (IPV) before the global withdrawal of serotype 2 OPV in 2016. A 1- or 2-dose schedule, potentially administered intradermally with reduced antigen content, may make this affordable. Methods. A systematic review and meta-analysis of studies documenting seroconversion after 1 or 2, full or fractional (1/5) doses of enhanced-potency IPV was performed. Studies reporting the clinical efficacy of IPV were also reviewed. Results. Twenty study arms from 12 published articles were included in the analysis of seroconversion. One full dose of intramuscular IPV seroconverted 33%, 41%, and 47% of infants against serotypes 1, 2, and 3 on average, whereas 2 full doses seroconverted 79%, 80%, and 90%, respectively. Seroconversion increased with age at administration. Limited data from case-control studies indicate clinical efficacy equivalent to the proportion seroconverting. One fractional dose of intradermal IPV gave lower seroconversion (10%–40%), but after 2 doses seroconversion was comparable to that with full-dose IPV. Conclusions. Routine immunization with 2 full or fractional doses of IPV given after 10 weeks of age is likely to protect >80% of recipients against poliomyelitis if poliovirus reemerges after withdrawal of OPV serotypes. PMID:24634499

  14. Serial Recombination during Circulation of Type 1 Wild-Vaccine Recombinant Polioviruses in China

    PubMed Central

    Liu, Hong-Mei; Zheng, Du-Ping; Zhang, Li-Bi; Oberste, M. Steven; Kew, Olen M.; Pallansch, Mark A.

    2003-01-01

    Type 1 wild-vaccine recombinant polioviruses sharing a 367-nucleotide (nt) block of Sabin 1-derived sequence spanning the VP1 and 2A genes circulated widely in China from 1991 to 1993. We surveyed the sequence relationships among 34 wild-vaccine recombinants by comparing six genomic intervals: the conserved 5′-untranslated region (5′-UTR) (nt 186 to 639), the hypervariable portion of the 5′-UTR (nt 640 to 742), the VP4 and partial VP2 genes (nt 743 to 1176), the VP1 gene (nt 2480 to 3385), the 2A gene (nt 3386 to 3832), and the partial 3D gene (nt 6011 to 6544). The 5′-UTR, capsid (VP4-VP2 and VP1), and 2A sequence intervals had similar phylogenies. By contrast, the partial 3D sequences could be distributed into five divergent genetic classes. Most (25 of 34) of the wild-vaccine recombinant isolates showed no evidence of additional recombination beyond the initial wild-Sabin recombination event. Eight isolates from 1992 to 1993, however, appear to be derived from three independent additional recombination events, and one 1993 isolate was derived from two consecutive events. Complete genomic sequences of a representative isolate for each 3D sequence class demonstrated that these exchanges had occurred in the 2B, 2C, and 3D genes. The 3D gene sequences were not closely related to those of the Sabin strains or 53 diverse contemporary wild poliovirus isolates from China, but all were related to the 3D genes of species C enteroviruses. The appearance within approximately 2.5 years of five recombinant classes derived from a single ancestral infection illustrates the rapid emergence of new recombinants among circulating wild polioviruses. PMID:14512548

  15. Improved genotyping vaccine and wild-type poliovirus strains by restriction fragment length polymorphism analysis: clinical diagnostic implications.

    PubMed

    Georgopoulou, A; Markoulatos, P; Spyrou, N; Vamvakopoulos, N C

    2000-12-01

    The combination of preventive vaccination and diagnostic typing of viral isolates from patients with clinical poliomyelitis constitutes our main protective shield against polioviruses. The restriction fragment length polymorphism (RFLP) adaptation of the reverse transcriptase (RT)-PCR methodology has advanced diagnostic genotyping of polioviruses, although further improvements are definitely needed. We report here on an improved RFLP procedure for the genotyping of polioviruses. A highly conserved segment within the 5' noncoding region of polioviruses was selected for RT-PCR amplification by the UC(53)-UG(52) primer pair with the hope that it would be most resistant to the inescapable genetic alteration-drift experienced by the other segments of the viral genome. Complete inter- and intratypic genotyping of polioviruses by the present RFLP method was accomplished with a minimum set of four restriction endonucleases (HaeIII, DdeI, NcoI, and AvaI). To compensate for potential genetic drift within the recognition sites of HaeIII, DdeI, or NcoI in atypical clinical samples, the RFLP patterns generated with HpaII and StyI as replacements were analyzed. The specificity of the method was also successfully assessed by RFLP analysis of 55 reference nonpoliovirus enterovirus controls. The concerted implementation of these conditional protocols for diagnostic inter- and intratypic genotyping of polioviruses was evaluated with 21 clinical samples with absolute success. PMID:11101561

  16. Improved Genotyping Vaccine and Wild-Type Poliovirus Strains by Restriction Fragment Length Polymorphism Analysis: Clinical Diagnostic Implications

    PubMed Central

    Georgopoulou, Amalia; Markoulatos, Panayotis; Spyrou, Niki; Vamvakopoulos, Nicholas C.

    2000-01-01

    The combination of preventive vaccination and diagnostic typing of viral isolates from patients with clinical poliomyelitis constitutes our main protective shield against polioviruses. The restriction fragment length polymorphism (RFLP) adaptation of the reverse transcriptase (RT)-PCR methodology has advanced diagnostic genotyping of polioviruses, although further improvements are definitely needed. We report here on an improved RFLP procedure for the genotyping of polioviruses. A highly conserved segment within the 5′ noncoding region of polioviruses was selected for RT-PCR amplification by the UC53-UG52 primer pair with the hope that it would be most resistant to the inescapable genetic alteration-drift experienced by the other segments of the viral genome. Complete inter- and intratypic genotyping of polioviruses by the present RFLP method was accomplished with a minimum set of four restriction endonucleases (HaeIII, DdeI, NcoI, and AvaI). To compensate for potential genetic drift within the recognition sites of HaeIII, DdeI, or NcoI in atypical clinical samples, the RFLP patterns generated with HpaII and StyI as replacements were analyzed. The specificity of the method was also successfully assessed by RFLP analysis of 55 reference nonpoliovirus enterovirus controls. The concerted implementation of these conditional protocols for diagnostic inter- and intratypic genotyping of polioviruses was evaluated with 21 clinical samples with absolute success. PMID:11101561

  17. [Investigation of a Patient with Pre-vaccine-derived Poliovirus in Shandong Province, China].

    PubMed

    Lin, Xiaojuan; Liu, Yao; Wang, Suting; Zhang Xiao; Song, Lizhi; Tao, Zexin; Ji, Feng; Xiong, Ping; Xu, Aiqiang

    2015-09-01

    To analyze the genetic characteristics of a polio-I highly variant vaccine recombinant virus in Shandong Province (China) in 2011 and to identify isolates from healthy contacts, two stool specimens from one patient with acute flaccid paralysis (AFP) and 40 stool specimens from his contacts were collected for virus isolation. The complete genome of poliovirus and VP1 coding region of the non-polio enterovirus were sequenced. Homologous comparison and phylogenetic analyses based on VP1 sequences were undertaken among coxsackievirus (CV) B1, CV-B3 isolates, and those in GenBank. One poliovirus (P1/11186), CV-A4 and CV-A8 were isolated from the AFP patient; one CV-A2, Echovirus 3 (E-3), E-12 and E-14, ten CV-B1, and five CV-B3 strains were isolated from his contacts. These results led us to believe that there may be a human enterovirus epidemic in this area, and that surveillance must be enhanced. P1/11186 was a type-1 vaccine-related poliovirus; it combined with type-2 and type-3 polioviruses in 2A and 3A regions, respectively. There were 25 nucleotide mutations with 9 amino-acid alterations in the entire genome. There were 8 nucleotide mutations with 5 amino-acid alterations in the VP1 region compared with the corresponding Sabin strains. Homology analyses suggested that the ten CV-B1 isolates had 97.0%-100% nucleotide and 98.9%-100% amino-acid identities with each other, as well as 92.6%-100% nucleotide and 99.2%-100% amino-acid identities among the five CV-B3 isolates. Phylogenetic analyses on the complete sequences of VP1 among CV-B1 and CV-B3 isolates showed that Shandong strains, together with strains from other provinces in China, had a close relationship and belonged to the same group. PMID:26738293

  18. Controlled trial of immune response of preterm infants to recombinant hepatitis B and inactivated poliovirus vaccines administered simultaneously shortly after birth

    PubMed Central

    Linder, N.; Handsher, R.; German, B.; Sirota, L.; Bachman, M.; Zinger, S.; Mendelson, E.; Barzilai, A.

    2000-01-01

    AIM—The study was conducted to evaluate the immunogenicity of an early, extra dose of enhanced inactivated poliovirus vaccine (IPV) administered simultaneously with recombinant hepatitis B vaccine (HBV) to preterm infants shortly after birth.
METHODS—Three groups were studied. Fifty preterm infants received IPV intramuscularly within 24 hours of birth, in addition to routine recommended childhood immunisations. Fifty two preterm infants and 35 full term infants received routine immunisations only (routine vaccination timing: HBV at birth, 1 and 6 months of age; IPV at 2 and 4 months; oral polio vaccine (OPV) at 4 and 6 months; diphtheria-tetanus-pertussis (DTP) at 2, 4, and 6 months; and Haemophilus influenzae B vaccine at 2 and 4 months). Blood samples were taken at birth, 3 and 7months of age from all infants, and at 1 month of age from preterm infants only.
RESULTS—At birth, a lower percentage of both study and control preterm infants had antipoliovirus type 3 titres ⩾ 1:8 than full term infants. At 1 and 3 months of age significantly more early IPV infants had antipoliovirus type 3 titres ⩾ 1:8 than routinely vaccinated preterm infants (p < 0.05). At 7 months of age there were no significant differences in percentage of antipoliovirus titres ⩾ 1:8 or geometric mean times (GMTs) between the early IPV group and the routinely vaccinated preterm group. At 3 and 7 months of age, the percentage of positive antihepatitis B titres (⩾ 1:10) and the GMT of the early IPV preterm group did not differ significantly from those of preterm controls. There was no significant difference in percentage of positive antihepatitis B titres between the early IPV group and full term controls at any time. GMTs for hepatitis B antibodies were significantly lower in the early IPV preterm group than in full term controls at 3 and 7 months of age.
CONCLUSIONS—Administration of an additional dose of IPV simultaneously with routine HBV to preterm infants shortly after

  19. Rare natural type 3/type 2 intertypic capsid recombinant vaccine-related poliovirus isolated from a case of acute flaccid paralysis in Brazil, 2015.

    PubMed

    Cassemiro, Klécia M S M; Burlandy, Fernanda M; da Silva, Edson E

    2016-07-01

    A natural type 3/type 2 intertypic capsid recombinant vaccine-related poliovirus was isolated from an acute flaccid paralytic case in Brazil. Genome sequencing revealed the uncommon location of the crossover site in the VP1 coding region (nucleotides 3251-3258 of Sabin 3 genome). The Sabin 2 donor sequence replaced the last 118 nt of VP1, resulting in the substitution of the complete antigenic site IIIa by PV2-specific amino acids. The low overall number of nucleotide substitutions in P1 region indicated that the predicted replication time of the isolate was about 8-9 weeks. Two of the principal determinants of attenuation in Sabin 3 genomes were mutated (U472C and C2493U), but the temperature-sensitive phenotype of the isolate was preserved. Our results support the theory that there exists a PV3/PV2 recombination hotspot site in the tail region of the VP1 capsid protein and that the recombination may occur soon after oral poliovirus vaccine administration. PMID:27082658

  20. Isolation and Characterization of a Type 2 Vaccine-Derived Poliovirus from Environmental Surveillance in China, 2012

    PubMed Central

    Liu, Yao; Xu, Aiqiang; Lin, Xiaojuan; Yoshida, Hiromu; Xiong, Ping; Zhu, Shuangli; Wang, Suting; Yan, Dongmei; Song, Lizhi; Wang, Haiyan; Cui, Ning; Xu, Wenbo

    2013-01-01

    Environmental surveillance of poliovirus on sewage has been conducted in Shandong Province, China since 2008. A type 2 vaccine-derived poliovirus (VDPV) with 7 mutations in VP1 coding region was isolated from the sewage collected in the city of Jinan in December 2012. The complete genome sequencing analysis of this isolate revealed 25 nucleotide substitutions, 7 of which resulted in amino acid alteration. No evidence of recombination with other poliovirus serotypes was observed. The virus did not lose temperature sensitive phenotype at 40°C. An estimation based on the evolution rate of the P1 coding region suggested that evolution time of this strain might be 160–176 days. VP1 sequence analysis revealed that this VDPV strain is of no close relationship with other local type 2 polioviruses (n = 66) from sewage collected between May 2012 and June 2013, suggesting the lack of its circulation in the local population. The person who excreted the virus was not known and no closely related virus was isolated in local population via acute flaccid paralysis surveillance. By far this is the first report of VDPV isolated from sewage in China, and these results underscore the value of environmental surveillance in the polio surveillance system even in countries with high rates of OPV coverage. PMID:24386319

  1. Recent advances in oral vaccine development

    PubMed Central

    De Smet, Rebecca; Allais, Liesbeth; Cuvelier, Claude A

    2014-01-01

    Oral vaccination is the most challenging vaccination method due to the administration route. However, oral vaccination has socio-economic benefits and provides the possibility of stimulating both humoral and cellular immune responses at systemic and mucosal sites. Despite the advantages of oral vaccination, only a limited number of oral vaccines are currently approved for human use. During the last decade, extensive research regarding antigen-based oral vaccination methods have improved immunogenicity and induced desired immunological outcomes. Nevertheless, several factors such as the harsh gastro-intestinal environment and oral tolerance impede the clinical application of oral delivery systems. To date, human clinical trials investigating the efficacy of these systems are still lacking. This review addresses the rationale and key biological and physicochemical aspects of oral vaccine design and highlights the use of yeast-derived β-glucan microparticles as an oral vaccine delivery platform. PMID:24553259

  2. Pollen grains for oral vaccination

    PubMed Central

    Atwe, Shashwati U.; Ma, Yunzhe; Gill, Harvinder Singh

    2015-01-01

    Oral vaccination can offer a painless and convenient method of vaccination. Furthermore, in addition to systemic immunity it has potential to stimulate mucosal immunity through antigen-processing by the gut-associated lymphoid tissues. In this study we propose the concept that pollen grains can be engineered for use as a simple modular system for oral vaccination. We demonstrate feasibility of this concept by using spores of Lycopodium clavatum (clubmoss) (LSs). We show that LSs can be chemically cleaned to remove native proteins to create intact clean hollow LS shells. Empty pollen shells were successfully filled with molecules of different sizes demonstrating their potential to be broadly applicable as a vaccination system. Using ovalbumin (OVA) as a model antigen, LSs formulated with OVA were orally fed to mice. LSs stimulated significantly higher anti-OVA serum IgG and fecal IgA antibodies compared to those induced by use of cholera toxin as a positive-control adjuvant. The antibody response was not affected by pre-neutralization of the stomach acid, and persisted for up to seven months. Confocal microscopy revealed that LSs can translocate in to mouse intestinal wall. Overall, this study lays the foundation of using LSs as a novel approach for oral vaccination. PMID:25151980

  3. Pollen grains for oral vaccination.

    PubMed

    Atwe, Shashwati U; Ma, Yunzhe; Gill, Harvinder Singh

    2014-11-28

    Oral vaccination can offer a painless and convenient method of vaccination. Furthermore, in addition to systemic immunity it has potential to stimulate mucosal immunity through antigen-processing by the gut-associated lymphoid tissues. In this study we propose the concept that pollen grains can be engineered for use as a simple modular system for oral vaccination. We demonstrate feasibility of this concept by using spores of Lycopodium clavatum (clubmoss) (LSs). We show that LSs can be chemically cleaned to remove native proteins to create intact clean hollow LS shells. Empty pollen shells were successfully filled with molecules of different sizes demonstrating their potential to be broadly applicable as a vaccination system. Using ovalbumin (OVA) as a model antigen, LSs formulated with OVA were orally fed to mice. LSs stimulated significantly higher anti-OVA serum IgG and fecal IgA antibodies compared to those induced by use of cholera toxin as a positive-control adjuvant. The antibody response was not affected by pre-neutralization of the stomach acid, and persisted for up to 7 months. Confocal microscopy revealed that LSs can translocate into mouse intestinal wall. Overall, this study lays the foundation of using LSs as a novel approach for oral vaccination. PMID:25151980

  4. Sporadic Isolation of Sabin-Like Polioviruses and High-Level Detection of Non-Polio Enteroviruses during Sewage Surveillance in Seven Italian Cities, after Several Years of Inactivated Poliovirus Vaccination

    PubMed Central

    Battistone, A.; Buttinelli, G.; Fiore, S.; Amato, C.; Bonomo, P.; Patti, A. M.; Vulcano, A.; Barbi, M.; Binda, S.; Pellegrinelli, L.; Tanzi, M. L.; Affanni, P.; Castiglia, P.; Germinario, C.; Mercurio, P.; Cicala, A.; Triassi, M.; Pennino, F.

    2014-01-01

    Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5′ noncoding region (5′NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile > Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing. PMID:24814793

  5. Sporadic isolation of sabin-like polioviruses and high-level detection of non-polio enteroviruses during sewage surveillance in seven Italian cities, after several years of inactivated poliovirus vaccination.

    PubMed

    Battistone, A; Buttinelli, G; Fiore, S; Amato, C; Bonomo, P; Patti, A M; Vulcano, A; Barbi, M; Binda, S; Pellegrinelli, L; Tanzi, M L; Affanni, P; Castiglia, P; Germinario, C; Mercurio, P; Cicala, A; Triassi, M; Pennino, F; Fiore, L

    2014-08-01

    Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5'noncoding region (5'NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile>Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing. PMID:24814793

  6. [Genetic Characteristics of Type 2 Vaccine-derived Poliovirus in Shanxi Province (China) in 2014].

    PubMed

    Yan, Dongrei; Li, Xiaolei; Zhang, Yong; Yang, Jianfang; Zhu, Shuangli; Wang, Dongyan; Zhang, Chuangye; Zhu, Hui; Xu, Wenbo

    2015-03-01

    The World Health Organization redefined the type 2 vaccine-derived poliovirus (VDPV) in 2010. To study the genetic characteristics and evolution of type 2 VDPV under this new definition, we conducted genome sequencing and analyses of type 2 VDPVs isolated from one patient with acute flaccid paralysis in Shanxi province (China) in 2014. Nucleotide sequencing revealed that the full-length of type 2 VDPV is 7439 bases encoding 2207 amino acids with no insertion or deletion of nucleotides compared with Sabin2. One nucleotide substitution identified as a key determinant of the attenuated phenotype of the Sabin 2 strain (A-G reversion at nucleotide nt 481 in the 5-end of the untranslated region) had reverted in the Shanxi type 2 VDPV. The other known key determinant of the attenuated phenotype of the Sabin 2 strain (U-->C reversion at nt2909 in the VP1 coding region that caused a Ile143Thr substitution in VP1) had not reverted in the Shanxi VDPV. The Shanxi type 2 VDPV was S2/S1 recombinant, the crossover site of which mapped to the 3-end of the 3D region (between nt 6247 and nt 6281). A phylogentic tree based on the VP1 coding region showed that evolution of the Shanxi type 2 VDPV was independent of other type 2 VDPVs detected worldwide. We estimated that the strain circulated for approximately = 11 months in the population according to the known evolution rate. The present study confirmed that the Chinese Polio Laboratory Network could discover the VDPV promptly and that it played an important part in maintenance of a polio-free China. PMID:26164941

  7. Importation and circulation of poliovirus in Bulgaria in 2001.

    PubMed Central

    Kojouharova, Mira; Zuber, Patrick L. F.; Gyurova, Snejana; Fiore, Lucia; Buttinelli, Gabriele; Kunchev, Angel; Vladimirova, Nadejda; Korsun, Neli; Filipova, Radosveta; Boneva, Roumiana; Gavrilin, Eugene; Deshpande, Jagadish M.; Oblapenko, George; Wassilak, Steven G.

    2003-01-01

    OBJECTIVE: To characterize the circumstances in which poliomyelitis occurred among three children in Bulgaria during 2001 and to describe the public health response. METHODS: Bulgarian authorities investigated the three cases of polio and their contacts, conducted faecal and serological screening of children from high-risk groups, implemented enhanced surveillance for acute flaccid paralysis, and conducted supplemental immunization activities. FINDINGS: The three cases of polio studied had not been vaccinated and lived in socioeconomically deprived areas of two cities. Four Roma children from the Bourgas district had antibody titres to serotype 1 poliovirus only, and wild type 1 virus was isolated from the faeces of two asymptomatic Roma children in the Bourgas and Sofia districts. Poliovirus isolates were related genetically and represented a single evolutionary lineage; genomic sequences were less than 90% identical to poliovirus strains isolated previously in Europe, but 98.3% similar to a strain isolated in India in 2000. No cases or wild virus isolates were found after supplemental immunization activities were launched in May 2001. CONCLUSIONS: In Bulgaria, an imported poliovirus was able to circulate for two to five months among minority populations. Surveillance data strongly suggest that wild poliovirus circulation ceased shortly after supplemental immunization activities with oral poliovirus vaccine were conducted. PMID:12973639

  8. Pioneering figures in medicine: Albert Bruce Sabin--inventor of the oral polio vaccine.

    PubMed

    Smith, Derek R; Leggat, Peter A

    2005-01-01

    Over ten years after his death, the Sabin oral vaccine continues its profound influence on public health throughout the world. The annual incidence of polio has fallen dramatically since its introduction, with more than 300,000 lives being spared each year and an annual global saving in excess of 1 billion US dollars. In many ways, the development of an effective oral vaccine and its subsequent regulation by the World Health Organization can serve as a model for medical researchers. Our review describes the contribution of Albert Sabin as a medical researcher, and how his vaccine had a profound impact on the global reduction of polio infections. As many different factors influenced health-care last century, we describe Sabin's involvement with respect to prevailing scientific paradigms and public health issues of the time. Our paper also outlines the basic epidemiology of poliovirus and the historical development of an effective vaccine, both with and without Albert Sabin. PMID:16422178

  9. Progress in the development of poliovirus antiviral agents and their essential role in reducing risks that threaten eradication.

    PubMed

    McKinlay, Mark A; Collett, Marc S; Hincks, Jeffrey R; Oberste, M Steven; Pallansch, Mark A; Okayasu, Hiromasa; Sutter, Roland W; Modlin, John F; Dowdle, Walter R

    2014-11-01

    Chronic prolonged excretion of vaccine-derived polioviruses by immunodeficient persons (iVDPV) presents a personal risk of poliomyelitis to the patient as well as a programmatic risk of delayed global eradication. Poliovirus antiviral drugs offer the only mitigation of these risks. Antiviral agents may also have a potential role in the management of accidental exposures and in certain outbreak scenarios. Efforts to discover and develop poliovirus antiviral agents have been ongoing in earnest since the formation in 2007 of the Poliovirus Antivirals Initiative. The most advanced antiviral, pocapavir (V-073), is a capsid inhibitor that has recently demonstrated activity in an oral poliovirus vaccine human challenge model. Additional antiviral candidates with differing mechanisms of action continue to be profiled and evaluated preclinically with the goal of having 2 antivirals available for use in combination to treat iVDPV excreters. PMID:25316866

  10. Managing population immunity to reduce or eliminate the risks of circulation following the importation of polioviruses.

    PubMed

    Thompson, Kimberly M; Kalkowska, Dominika A; Duintjer Tebbens, Radboud J

    2015-03-24

    Poliovirus importations into polio-free countries represent a major concern during the final phases of global eradication of wild polioviruses (WPVs). We extend dynamic transmission models to demonstrate the dynamics of population immunity out through 2020 for three countries that only used inactivated poliovirus vaccine (IPV) for routine immunization: the US, Israel, and The Netherlands. For each country, we explore the vulnerability to re-established transmission following an importation for each poliovirus serotype, including the impact of immunization choices following the serotype 1 WPV importation that occurred in 2013 in Israel. As population immunity declines below the threshold required to prevent transmission, countries become at risk for re-established transmission. Although importations represent stochastic events that countries cannot fully control because people cross borders and polioviruses mainly cause asymptomatic infections, countries can ensure that any importations die out. Our results suggest that the general US population will remain above the threshold for transmission through 2020. In contrast, Israel became vulnerable to re-established transmission of importations of live polioviruses by the late 2000s. In Israel, the recent WPV importation and outbreak response use of bivalent oral poliovirus vaccine (bOPV) eliminated the vulnerability to an importation of poliovirus serotypes 1 and 3 for several years, but not serotype 2. The Netherlands experienced a serotype 1 WPV outbreak in 1992-1993 and became vulnerable to re-established transmission in religious communities with low vaccine acceptance around the year 2000, although the general population remains well-protected from widespread transmission. All countries should invest in active management of population immunity to avoid the potential circulation of imported live polioviruses. IPV-using countries may wish to consider prevention opportunities and/or ensure preparedness for response

  11. A survey for neutralizing antibodies to the three types of poliovirus among children in Maiduguri, Nigeria.

    PubMed

    Baba, M M; Haruna, B A; Ogunmola, O; Ambe, J P; Shidali, N N; Oderinde, B; Marcello, A; Talle, M

    2012-04-01

    The milestone in polio eradication program is to protect effectively children aged 0-5 years against the three serotypes of poliovirus. It became necessary to measure the level of neutralizing antibodies to the three poliovirus types in an endemic State in Nigeria. Neutralizing antibodies to the poliovirus types among children aged 0-5 years was estimated using micro neutralization assay. Of 129 children, 99 (76.8%), 95 (73.6%), and 95 (73.6%) had neutralizing antibodies with the geometric mean titer of 42.7, 31.3, and 33.2 for the poliovirus type 1, 2, and 3, respectively. Fifty-three percent of the children were protected against the three types of poliovirus. Combination of poliovirus types 1 and 2, 1 and 3, and 2 and 3 were neutralized by 62.8, 58.9, and 61.2% of the children studied, respectively. Only poliovirus type 1 induced antibody titres ≥1:1,024. The number of children with neutralizing antibodies after receiving three doses was significantly higher than those who received one or two doses of oral polio vaccine (P ≤ 0.05). However, those who received more than three doses of oral polio vaccine showed no significant difference in their antibody response. The existence of immunity gap poses a risk of re-emergence of the paralytic poliovirus. The existence of unimmunized and unprotected children along with high birth rate could impede the success of polio vaccination in Nigeria. Elimination of non-compliance to polio vaccine, promotion of health education and documented evidence of vaccination of each child with the parents may facilitate the success of polio eradication program in Nigeria. PMID:22337311

  12. Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus

    PubMed Central

    Verma, Harish; Sharma, Prashant; Yang, Jae Seung; Saletti, Giulietta; Ahmad, Mohammad; Bahl, Sunil K.; Wierzba, Thomas F.; Nandy, Ranjan K.; Deshpande, Jagadish M.; Sutter, Roland W.; Czerkinsky, Cecil

    2016-01-01

    Background The “gold standard” for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine. Methods 199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4β7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation. Results An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, α4β7+ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive α4β7+ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4β7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for

  13. Molecular and Phenotypic Characterization of a Highly Evolved Type 2 Vaccine-Derived Poliovirus Isolated from Seawater in Brazil, 2014

    PubMed Central

    Cassemiro, Klécia Marília S. de Melo; Burlandy, Fernanda M.; Barbosa, Mikaela R. F.; Chen, Qi; Jorba, Jaume; Hachich, Elayse M.; Sato, Maria I. Z.; Burns, Cara C.; da Silva, Edson E.

    2016-01-01

    A type 2 vaccine-derived poliovirus (VDPV), differing from the Sabin 2 strain at 8.6% (78/903) of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C). The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg) sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication. PMID:27019095

  14. SAG-2 oral rabies vaccine.

    PubMed

    Schumacher, C L; Coulon, P; Lafay, F; Bénéjean, J; Aubert, M F; Barrat, J; Aubert, A; Flamand, A

    1993-12-01

    The live modified rabies virus vaccine strain SAG-2 was selected from SADBerne in a two step process employing anti-rabies glycoprotein monoclonal antibodies. The first two nucleotides coding for the amino acid in position 333 of the rabies glycoprotein are mutated. Arginine at position 333, which is associated with rabies pathogenicity, was substituted first by lysine and then by glutamic acid. The two nucleotide differences at position 333 in SAG-2 to any of six possible arginine triplets translated into excellent genetic stability and apathogenicity for adult mice, foxes, cats and dogs. The vaccination of foxes and dogs by the oral route provided protection against a lethal challenge with rabies virus. PMID:7777336

  15. A severe case of co-infection with Enterovirus 71 and vaccine-derived Poliovirus type II.

    PubMed

    Ma, Shaohui; Du, Zengqing; Feng, Min; Che, Yanchun; Li, Qihan

    2015-11-01

    Enterovirus 71 (EV71) is often identified as the primary pathogen that directly leads to severe cases of HFMD, whereas the association between other enteroviruses and EV71 infection remains largely unclear. Here we report a rare case of a 5-year-old boy co-infected with EV71 and vaccine-derived Poliovirus (VDPV) type II, which were identified based on PCR and sequence analysis results and clinical symptoms and were characterized on CT. We determined that the EV71 strain belongs to the C4 subtype, and the VDPV II strain was closely genetically related to the reference Sabin type II strain. This report may improved our understanding of the clinical significance of the associations between clinical signs and the infectious properties of the involved pathogens. PMID:26361010

  16. Contribution of Environmental Surveillance Toward Interruption of Poliovirus Transmission in Nigeria, 2012–2015

    PubMed Central

    Johnson Muluh, Ticha; Hamisu, Abdullahi Walla; Craig, Kehinde; Mkanda, Pascal; Andrew, Etsano; Adeniji, Johnson; Akande, Adefunke; Musa, Audu; Ayodeji, Isiaka; Nicksy, Gumede; Banda, Richard; Tegegne, Sisay G.; Nsubuga, Peter; Oyetunji, Ajiboye; Diop, Ousmane; Vaz, Rui G.; Muhammad, Ado J. G.

    2016-01-01

    Background. Cases of paralysis caused by poliovirus have decreased by >99% since the 1988 World Health Assembly's resolution to eradicate polio. The World Health Organization identified environmental surveillance (ES) of poliovirus in the poliomyelitis eradication strategic plan as an activity that can complement acute flaccid paralysis (AFP) surveillance. This article summarizes key public health interventions that followed the isolation of polioviruses from ES between 2012 and 2015. Methods. The grap method was used to collect 1.75 L of raw flowing sewage every 2–4 weeks. Once collected, samples were shipped at 4°C to a polio laboratory for concentration. ES data were then used to guide program implementation. Results. From 2012 to 2015, ES reported 97 circulating vaccine-derived polioviruses (cVDPV2) and 14 wild polioviruses. In 2014 alone, 54 cVDPV type 2 cases and 1 WPV type 1 case were reported. In Sokoto State, 58 cases of AFP were found from a search of 9426 households. A total of 2 252 059 inactivated polio vaccine and 2 460 124 oral polio vaccine doses were administered to children aged <5 year in Borno and Yobe states. Conclusions. This article is among the first from Africa that relates ES findings to key public health interventions (mass immunization campaigns, inactivated polio vaccine introduction, and strengthening of AFP surveillance) that have contributed to the interruption of poliovirus transmission in Nigeria. PMID:26908747

  17. Future of Polio Vaccines

    PubMed Central

    2009-01-01

    Summary Over the past half-century, global use of highly effective vaccines against poliomyelitis brought this disease to the brink of elimination. Mounting evidence argues that a high level of population immunity must be maintained to preserve a polio-free status of the entire world after wild poliovirus circulation is stopped. Shifting factors in the risk-benefit-cost equation favor the creation of new poliovirus vaccines to be used in the foreseeable future. Genetically stable attenuated virus strains could be developed for an improved oral poliovirus vaccine, but proving their safety and efficacy would be impractical because of the enormous size of the clinical trials required. New versions of inactivated poliovirus vaccine (IPV) that could be used globally should be developed. An improved IPV must be efficacious, inexpensive, safe to manufacture, and easy to administer. Combination products containing IPV along with other protective antigens should become part of routine childhood immunizations around the world. PMID:19545205

  18. Vaccine-associated paralytic poliomyelitis in India during 1999: decreased risk despite massive use of oral polio vaccine.

    PubMed Central

    Kohler, Kathryn A.; Banerjee, Kaushik; Gary Hlady, W.; Andrus, Jon K.; Sutter, Roland W.

    2002-01-01

    OBJECTIVE: Vaccine-associated paralytic poliomyelitis (VAPP) is a rare but serious consequence of the administration of oral polio vaccine (OPV). Intensified OPV administration has reduced wild poliovirus transmission in India but VAPP is becoming a matter of concern. METHODS: We analysed acute flaccid paralysis (AFP) surveillance data in order to estimate the VAPP risk in this country. VAPP was defined as occurring in AFP cases with onset of paralysis in 1999, residual weakness 60 days after onset, and isolation of vaccine-related poliovirus. Recipient VAPP cases were a subset with onset of paralysis between 4 and 40 days after receipt of OPV. FINDINGS: A total of 181 AFP cases met the case definition. The following estimates of VAPP risk were made: overall risk, 1 case per 4.1 to 4.6 million OPV doses administered; recipient risk,1 case per 12.2 million; first-dose recipient risk, 1 case per 2.8 million; and subsequent-dose recipient risk, 1 case per 13.9 million. CONCLUSION: On the basis of data from a highly sensitive surveillance system the estimated VAPP risk in India is evidently lower than that in other countries, notwithstanding the administration of multiple OPV doses to children in mass immunization campaigns. PMID:11984607

  19. Framework for evaluating the risks of paralytic poliomyelitis after global interruption of wild poliovirus transmission.

    PubMed Central

    Aylward, R. Bruce; Cochi, Stephen L.

    2004-01-01

    With the interruption of wild poliovirus transmission globally, the need for new policies to deal with the post-certification era will rapidly arise. New policies will be required in four areas: detection and notification of circulating polioviruses; biocontainment of wild, vaccine-derived and attenuated strains of poliovirus; vaccine stockpiles and response mechanisms; and routine immunization against polioviruses. A common understanding of the potential risks of paralytic poliomyelitis in the post-certification period is essential to the development of these policies. Since 2000, there has been increasing international consensus that the risks of paralytic poliomyelitis in the post-certification era fall into two categories: those due to the continued use of the oral poliovirus vaccine (OPV) and those due to future improper handling of wild polioviruses. The specific risks within both categories have now been defined, and an understanding of the frequency and potential burden of disease associated with each is rapidly improving. This knowledge and clarity have provided a framework that is already proving valuable for identifying research priorities and discussing potential policy options with national authorities. However, this framework must be regarded as a dynamic tool, requiring regular updating as additional information on these risks becomes available through further scientific research, programmatic work, and policy decisions. PMID:15106299

  20. Oral vaccination of dogs with recombinant rabies virus vaccines.

    PubMed

    Rupprecht, Charles E; Hanlon, Cathleen A; Blanton, Jesse; Manangan, Jamie; Morrill, Patricia; Murphy, Staci; Niezgoda, Michael; Orciari, Lillian A; Schumacher, Carolin L; Dietzschold, Bernhard

    2005-07-01

    Oral rabies virus (RV) vaccines are used to immunize a diversity of mammalian carnivores, but no single biological is effective for all major species. Recently, advances in reverse genetics have allowed the design of recombinant RV for consideration as new vaccines. The objective of this experiment was to examine the safety, immunogenicity and efficacy of recombinant RV vaccines administered to captive dogs by the oral route, compared to a commercial vaccinia-rabies glycoprotein (V-RG) recombinant virus vaccine. Animals consisted of naive purpose-bred beagles of both sexes, and were 6 months of age or older. Dogs were randomly assigned to one of six groups, and received either diluent or vaccine (PBS; V-RG; RV SN10-333; RV SPBN-Cyto c; RV SPBNGA; RV SPBNGAGA), with at least six animals per group. On day 0, 1 ml of each vaccine (or PBS) was administered to the oral cavity of each dog, at an approximate concentration of 10(8) to 10(9) TCID50. After vaccination, dogs were observed daily and bled weekly, for 5 weeks, prior to RV challenge. No signs of illness related to vaccination were detected during the observation period. Excluding the controls, RV neutralizing antibodies were detected in the majority of animals within 1-2 weeks of primary vaccination. Thereafter, all dogs were inoculated in the masseter muscle with a street virus of canine origin. All control animals developed rabies, but no vaccinates succumbed, with the exception of a single dog in the V-RG group. Review of these preliminary data demonstrates the non-inferiority of recombinant RV products, as concerns both safety and efficacy, and supports the suggestion that these vaccines may hold promise for future development as oral immunogens for important carnivore species, such as dogs. PMID:15896409

  1. Booster vaccination of pre-school children with reduced-antigen-content diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine co-administered with measles-mumps-rubella-varicella vaccine

    PubMed Central

    Ferrera, Giuseppe; Cuccia, Mario; Mereu, Gabriele; Icardi, Giancarlo; Bona, Gianni; Esposito, Susanna; Marchetti, Federico; Messier, Marc; Kuriyakose, Sherine; Hardt, Karin

    2012-01-01

    Background: Pertussis occurs in older children, adolescents and adults due to waning immunity after primary vaccination. Booster vaccination for pre-school children has been recommended in Italy since 1999. In this study (NCT00871000), the immunogenicity, safety and reactogenicity of a booster dose of reduced-antigen content diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (dTpa-IPV; GSK Biologicals Boostrix™-Polio; 3-component pertussis) vs. full-strength DTPa-IPV vaccine (sanofi-pasteur—MSD Tetravac™; 2-component pertussis) was evaluated in pre-school Italian children.   Methods: Healthy children aged 5–6 y primed in a routine vaccination setting with three doses of DTPa-based vaccines were enrolled and randomized (1:1) in this phase IIIb, booster study to receive a single dose of dTpa-IPV or DTPa-IPV; the MMRV vaccine was co-administered. Antibody concentrations/titers against diphtheria, tetanus, pertussis and poliovirus 1–3 were measured before and one month post-booster. Reactogenicity and safety was assessed. Results: 305 subjects were enrolled of whom 303 (dTpa-IPV = 151; DTPa-IPV = 152) received booster vaccination. One month post-booster, all subjects were seroprotected/seropositive for anti-diphtheria, anti-tetanus, anti-PT, anti-FHA and anti-poliovirus 1–3; 99.3% of dTpa-IPV and 60.4% of DTPa-IPV subjects were seropositive for anti-PRN; 98–100% of subjects were seropositive against MMRV antigens post-booster. Pain at the injection site (dTpa-IPV: 63.6%; DTPa-IPV: 63.2%) and fatigue (dTpa-IPV: 26.5%; DTPa-IPV: 23.7%) were the most commonly reported solicited local and general symptoms, during the 4-d follow-up period. No SAEs or fatalities were reported. Conclusions: The reduced-antigen-content dTpa-IPV vaccine was non-inferior to full-strength DTPa-IPV vaccine with respect to immunogenicity. The vaccine was well-tolerated and can be confidently used as a booster dose in pre-school children. PMID:22327497

  2. Alternative administration routes and delivery technologies for polio vaccines.

    PubMed

    Kraan, Heleen; van der Stel, Wanda; Kersten, Gideon; Amorij, Jean-Pierre

    2016-08-01

    Global polio eradication is closer than ever. Replacement of the live attenuated oral poliovirus vaccine (OPV) by inactivated poliovirus vaccine (IPV) is recommended to achieve complete eradication. Limited global production capacity and relatively high IPV costs compared to OPV spur the need for improved polio vaccines. The target product profile of these vaccines includes not only dose sparing but also high stability, which is important for stockpiling, and easy application important for (emergency) vaccination campaigns. In this review, the current status of alternative polio vaccine delivery strategies is given. Furthermore, we discuss the feasibility of these strategies by highlighting challenges, hurdles to overcome, and formulation issues relevant for optimal vaccine delivery. PMID:26912100

  3. Recombinant Baculovirus Associated with Bilosomes as an Oral Vaccine Candidate against HEV71 Infection in Mice

    PubMed Central

    Premanand, Balraj; Prabakaran, Mookkan; Kiener, Tanja K.; Kwang, Jimmy

    2013-01-01

    Background Human enterovirus 71 (HEV71) is one of the major pathogen responsible for hand, foot and mouth disease (HFMD). Currently no effective vaccine or antiviral drugs are available. Like poliovirus, EV71 is transmitted mainly by the feco-oral route. To date the majority of the studied EV71 vaccine candidates are administered parenterally. Injectable vaccines induce good systemic immunity but mucosal responses are often unsatisfactory, whereas mucosal vaccines provide both systemic and mucosal immunity. Therefore, oral immunization appears to be an attractive alternative to parenteral immunization. Methodology/Principal Findings In this report, we studied the efficacy of an orally administered vaccine candidate developed using recombinant baculovirus displaying VP1 (Bac-VP1) in a murine model. Gastrointestinal delivery of Bac-VP1 significantly induced VP1-specific humoral (IgG) and mucosal (IgA) immune responses. Further, we studied the efficacy of the Bac-VP1 associated with bilosomes and observed that the Bac-VP1 associated with bilosomes elicited significantly higher immune responses compared to bilosomes non-associated with Bac-VP1. However, mice immunized subcutaneously with live Bac-VP1 had significantly enhanced VP1 specific serum IgG levels and higher neutralizing antibody titers compared with mice orally immunized with live Bac-VP1 alone or associated with bilosomes. Conclusion Bilosomes have been shown to possess inherent adjuvant properties when associated with antigen. Therefore Bac-VP1 with bilosomes could be a promising oral vaccine candidate against EV71 infections. Thus, Bac-VP1 loaded bilosomes may provide a needle free, painless approach for immunization against EV71, thereby increasing patient compliance and consequently increasing vaccination coverage. PMID:23390538

  4. Community Circulation Patterns of Oral Polio Vaccine Serotypes 1, 2, and 3 After Mexican National Immunization Weeks

    PubMed Central

    Troy, Stephanie B.; Ferreyra-Reyes, Leticia; Huang, ChunHong; Sarnquist, Clea; Canizales-Quintero, Sergio; Nelson, Christine; Báez-Saldaña, Renata; Holubar, Marisa; Ferreira-Guerrero, Elizabeth; García-García, Lourdes; Maldonado, Yvonne A.

    2014-01-01

    Background. With wild poliovirus nearing eradication, preventing circulating vaccine-derived poliovirus (cVDPV) by understanding oral polio vaccine (OPV) community circulation is increasingly important. Mexico, where OPV is given only during biannual national immunization weeks (NIWs) but where children receive inactivated polio vaccine (IPV) as part of their primary regimen, provides a natural setting to study OPV community circulation. Methods. In total, 216 children and household contacts in Veracruz, Mexico, were enrolled, and monthly stool samples and questionnaires collected for 1 year; 2501 stool samples underwent RNA extraction, reverse transcription, and real-time polymerase chain reaction (PCR) to detect OPV serotypes 1, 2, and 3. Results. OPV was detected up to 7 months after an NIW, but not at 8 months. In total, 35% of samples collected from children vaccinated the prior month, but only 4% of other samples, contained OPV. Although each serotype was detected in similar proportions among OPV strains shed as a result of direct vaccination, 87% of OPV acquired through community spread was serotype 2 (P < .0001). Conclusions. Serotype 2 circulates longer and is transmitted more readily than serotypes 1 or 3 after NIWs in a Mexican community primarily vaccinated with IPV. This may be part of the reason why most isolated cVDPV has been serotype 2. PMID:24367038

  5. Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh

    PubMed Central

    Naylor, Caitlin; Lu, Miao; Haque, Rashidul; Mondal, Dinesh; Buonomo, Erica; Nayak, Uma; Mychaleckyj, Josyf C.; Kirkpatrick, Beth; Colgate, Ross; Carmolli, Marya; Dickson, Dorothy; van der Klis, Fiona; Weldon, William; Steven Oberste, M.; Ma, Jennie Z.; Petri, William A.

    2015-01-01

    Background Environmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh. Methods We conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647. Findings EE was present in greater than 80% of infants by 12 weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ < − 2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix® IgA positive individuals can be attributed to the selected biomarkers. Interpretation EE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine

  6. Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative

    PubMed Central

    Dunn, Glynis; Klapsa, Dimitra; Wilton, Thomas; Stone, Lindsay; Minor, Philip D.; Martin, Javier

    2015-01-01

    There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era. PMID:26313548

  7. Oral vaccination of fish: Lessons from humans and veterinary species.

    PubMed

    Embregts, Carmen W E; Forlenza, Maria

    2016-11-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines for mass vaccination of farmed fish species. Furthermore, using various examples from the human and veterinary vaccine development, we propose additional approaches to fish vaccine design also considering recent advances in fish mucosal immunology and novel molecular tools. Finally, we discuss the pros and cons of using the zebrafish as a pre-screening animal model to potentially speed up vaccine design and testing for aquaculture fish species. PMID:27018298

  8. Novel nanocarrier for oral Hepatitis B vaccine.

    PubMed

    Dinda, Amit K; Bhat, Madhusudan; Srivastava, Sandeep; Kottarath, Sarat K; Prashant, Chandravilas K

    2016-06-01

    Oral vaccination is a safe, cost effective and non-invasive method suitable for mass immunization. We fabricated nanoparticle (NP) with 14kd polycaprolactone (PCL) entrapping hepatitis B surface antigen (HBsAg) stabilized with Pluronics® F127 and used it as oral delivery vehicle. We evaluated its efficacy for specific antibody production and compared with parenteral routes of immunization in mice. We found a superior antibody response with a higher titer of anti-HBsAg antibody till 2 months following single oral administration compared to other routes of immunization and conventional alum-based HBsAg vaccine. The NPs with the antigen were found in the macrophages in small intestinal villi, peripheral lymph nodes and other reticulo-endothelial organs 2 months after oral administration. This study suggests the efficacy of the current nanocarrier system for efficient antigen presentation disseminated in peripheral lymphoid tissues following oral administration with a prolonged antibody response, which can minimize the requirement of booster dose. PMID:27156634

  9. Preliminary report on vaccination in Croatia against poliomyelitis with type 1 (CHAT) and type 3 (W-Fox) attenuated polioviruses of Koprowski

    PubMed Central

    Ikić, D.; Jančikić, B.; Lulić, V.; Ćuk, D.; Juzbašić, M.; Manhalter, T.; Sindik, A.

    1963-01-01

    The incidence of poliomyelitis in the People's Republic of Croatia has progressively increased since 1945, and in 1953 and 1960 there were serious epidemics. In order to protect the age-groups at greatest risk a mass vaccination campaign was carried out with Koprowski live-virus vaccine in the early spring of 1961, covering the entire population aged 3 months to 20 years. Altogether 1 339 244 persons were given type 1 (CHAT strain), and 1 287 909 received type 3 (W-Fox). Over 100 000 persons were estimated to possess no pre-existing antibody to any of the three types of poliovirus. Although no unvaccinated control group was set up, it is considered that the epidemiological and serological data indicate the safety and efficacy of the vaccination. The serological conversion rate was 91.5% for type 1 and 93.5% for type 3. No post-vaccinal reactions were observed. The usual summer peak in incidence did not occur in 1961, altogether 6 cases being recorded from June (when immunity is considered to have been established) to December. This is the lowest figure since 1945. PMID:20604139

  10. Annual report of the Australian National Poliovirus Reference Laboratory, 2009.

    PubMed

    Roberts, Jason A; Hobday, Linda; Polychronopoulos, Sophie; Ibrahim, Aishah; Thorley, Bruce R

    2010-09-01

    The Australian National Poliovirus Reference Laboratory (NPRL) is accredited by the World Health Organization (WHO) for the testing of faecal specimens from acute flaccid paralysis (AFP) cases and operates as a regional poliovirus reference laboratory for the Western Pacific Region. The NPRL, in collaboration with the Australian Paediatric Surveillance Unit, co-ordinates surveillance for cases of AFP in children in Australia, according to criteria recommended by the WHO. Specimens are referred from AFP cases in children and suspected cases of poliomyelitis in persons of any age. The WHO AFP surveillance performance indicator is 1 non-polio AFP case per 100,000 children less than 15 years of age. In 2009, the Polio Expert Committee classified 48 cases as non-polio AFP, a rate of 1.17 cases per 100,000 children less than 15 years of age. An additional WHO AFP surveillance performance indicator is that more than 80% of notified AFP cases have 2 faecal samples collected 24 hours apart and within 14 days of onset of paralysis. Adequate faecal samples were received from 16 (33.3%) of the 48 classified cases. A poliovirus was referred via the Enterovirus Reference Laboratory Network of Australia from a non-AFP case and was determined to be Sabin-like. This case most likely represents an importation event, the source of which was not identified, as Australia ceased using Sabin oral polio vaccine in 2005. The last report of a wild poliovirus importation in Australia was from Pakistan in 2007. In 2009, 1,604 wild poliovirus cases were reported in 23 countries with Afghanistan, India, Nigeria and Pakistan remaining endemic for poliomyelitis. PMID:21090182

  11. Use of a Novel Real-Time PCR Assay To Detect Oral Polio Vaccine Shedding and Reversion in Stool and Sewage Samples after a Mexican National Immunization Day▿

    PubMed Central

    Troy, Stephanie B.; Ferreyra-Reyes, Leticia; Huang, ChunHong; Mahmud, Nadim; Lee, Yu-Jin; Canizales-Quintero, Sergio; Flaster, Harry; Báez-Saldaña, Renata; García-García, Lourdes; Maldonado, Yvonne

    2011-01-01

    During replication, oral polio vaccine (OPV) can revert to neurovirulence and cause paralytic poliomyelitis. In individual vaccinees, it can acquire specific revertant point mutations, leading to vaccine-associated paralytic poliomyelitis (VAPP). With longer replication, OPV can mutate into vaccine-derived poliovirus (VDPV), which causes poliomyelitis outbreaks similar to those caused by wild poliovirus. After wild poliovirus eradication, safely phasing out vaccination will likely require global use of inactivated polio vaccine (IPV) until cessation of OPV circulation. Mexico, where children receive routine IPV but where OPV is given biannually during national immunization days (NIDs), provides a natural setting to study the duration of OPV circulation in a population primarily vaccinated with IPV. We developed a real-time PCR assay to detect and distinguish revertant and nonrevertant OPV serotype 1 (OPV-1), OPV-2, and OPV-3 from RNA extracted directly from stool and sewage. Stool samples from 124 children and 8 1-liter sewage samples from Orizaba, Veracruz, Mexico, collected 6 to 13 weeks after a NID were analyzed. Revertant OPV-1 was found in stool at 7 and 9 weeks, and nonrevertant OPV-2 and OPV-3 were found in stool from two children 10 weeks after the NID. Revertant OPV-1 and nonrevertant OPV-2 and -3 were detected in sewage at 6 and 13 weeks after the NID. Our real-time PCR assay was able to detect small amounts of OPV in both stool and sewage and to distinguish nonrevertant and revertant serotypes and demonstrated that OPV continues to circulate at least 13 weeks after a NID in a Mexican population routinely immunized with IPV. PMID:21411577

  12. Current status of poliovirus infections.

    PubMed Central

    Melnick, J L

    1996-01-01

    Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the number of new cases is falling dramatically. It is hoped that by the year 2000, we will accomplish the goal of the World Health Organization of "a world without polio." Then, because there is no animal reservoir, we can seriously discuss when and how to eliminate the need for vaccination and ultimately destroy our stocks of poliovirus. PMID:8809461

  13. Current status of poliovirus infections.

    PubMed

    Melnick, J L

    1996-07-01

    Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the number of new cases is falling dramatically. It is hoped that by the year 2000, we will accomplish the goal of the World Health Organization of "a world without polio." Then, because there is no animal reservoir, we can seriously discuss when and how to eliminate the need for vaccination and ultimately destroy our stocks of poliovirus. PMID:8809461

  14. Orally delivered malaria vaccines: not too hard to swallow.

    PubMed

    Wang, Lina; Webster, Diane E; Wesselingh, Steven L; Coppel, Ross L

    2004-10-01

    Vaccines offer efficient and cost-effective protection against a wide range of infectious diseases. Unfortunately, no effective vaccine is yet available against malaria, and this infection remains one of the most important causes of human morbidity and mortality in the developing world. Over the past two decades a number of candidate proteins for inclusion in a subunit vaccine have been identified. Malariologists believe that an effective malaria vaccine will need to include multiple proteins that induce protective immune responses against different stages of the Plasmodium life cycle. The construction of such multivalent vaccines is beset by considerable logistical difficulties, not least of which is how to deliver them to a population living in endemic areas. Compared with other routes of vaccine administration, oral delivery has several advantages that make it an attractive strategy for vaccine development. This review summarises the progress towards an oral vaccine delivery system for malaria and discusses the feasibility of this approach. PMID:15461570

  15. Oral Rabies Vaccine Design for Expression in Plants.

    PubMed

    Singh, Ankit; Saxena, Gauri; Verma, Praveen C

    2016-01-01

    Vaccination is the sensitization process of the immune system against any pathogen. Generally, recombinant subunit vaccines are considered safer than attenuated vaccines. As whole pathogenic organisms are used in the immunization process, the attenuated vaccines are considered more risky than subunit vaccines. Rabies is the oldest known zoonosis which spreads through a neurotropic Lyssavirus primarily mediated through infected canine bites. Rabies causes worldwide loss of more than 60,000 human lives every year. Animal vaccination is equally important to check the transmission of rabies into humans. Rabies oral vaccination can be a good alternative where multiple booster and priming regimens are required while the painful vaccination process can continue for long durations. Introduction of oral vaccines was made to ease the discomfort associated with the mode of introduction of conventional vaccines into the body. Although the rabies oral vaccine can substantially reduce the cost of vaccination in the developing countries, mass immunization programs need larger quantities of vaccines which should be delivered at nominal cost. Expression of recombinant antigen proteins in E. coli is often not viable because of lack of post-translational modifications and folding requirements. Though yeast and insect cell line expression systems have post-translational processing and modifications, significantly different immunological response against their post-translational modification pattern limits their deployment as an expression system. As an alternative, plants are emerging as a promising system to express and deliver wide range of functionally active biopharmaceutical product at lower cost for mass immunization programs. As generation of vaccine antigenic proteins in plant systems are cheaper, the strategy will benefit developing countries where this disease causes thousands of deaths every year. In this chapter, we will discuss about our efforts toward development of oral

  16. Delivery strategies to enhance oral vaccination against enteric infections.

    PubMed

    Davitt, Christopher J H; Lavelle, Ed C

    2015-08-30

    While the majority of human pathogens infect the body through mucosal sites, most licensed vaccines are injectable. In fact the only mucosal vaccine that has been widely used globally for infant and childhood vaccination programs is the oral polio vaccine (OPV) developed by Albert Sabin in the 1950s. While oral vaccines against Cholera, rotavirus and Salmonella typhi have also been licensed, the development of additional non-living oral vaccines against these and other enteric pathogens has been slow and challenging. Mucosal vaccines can elicit protective immunity at the gut mucosa, in part via antigen-specific secretory immunoglobulin A (SIgA). However, despite their advantages over the injectable route, oral vaccines face many hurdles. A key challenge lies in design of delivery strategies that can protect antigens from degradation in the stomach and intestine, incorporate appropriate immune-stimulatory adjuvants and control release at the appropriate gastrointestinal site. A number of systems including micro and nanoparticles, lipid-based strategies and enteric capsules have significant potential either alone or in advanced combined formulations to enhance intestinal immune responses. In this review we will outline the opportunities, challenges and potential delivery solutions to facilitate the development of improved oral vaccines for infectious enteric diseases. PMID:25817337

  17. Mass vaccination with a two-dose oral cholera vaccine in a refugee camp.

    PubMed Central

    Legros, D.; Paquet, C.; Perea, W.; Marty, I.; Mugisha, N. K.; Royer, H.; Neira, M.; Ivanoff, B.

    1999-01-01

    In refugee settings, the use of cholera vaccines is controversial since a mass vaccination campaign might disrupt other priority interventions. We therefore conducted a study to assess the feasibility of such a campaign using a two-dose oral cholera vaccine in a refugee camp. The campaign, using killed whole-cell/recombinant B-subunit cholera vaccine, was carried out in October 1997 among 44,000 south Sudanese refugees in Uganda. Outcome variables included the number of doses administered, the drop-out rate between the two rounds, the proportion of vaccine wasted, the speed of administration, the cost of the campaign, and the vaccine coverage. Overall, 63,220 doses of vaccine were administered. At best, 200 vaccine doses were administered per vaccination site and per hour. The direct cost of the campaign amounted to US$ 14,655, not including the vaccine itself. Vaccine coverage, based on vaccination cards, was 83.0% and 75.9% for the first and second rounds, respectively. Mass vaccination of a large refugee population with an oral cholera vaccine therefore proved to be feasible. A pre-emptive vaccination strategy could be considered in stable refugee settings and in urban slums in high-risk areas. However, the potential cost of the vaccine and the absence of quickly accessible stockpiles are major drawbacks for its large-scale use. PMID:10593032

  18. An Insight into Recombination with Enterovirus Species C and Nucleotide G-480 Reversion from the Viewpoint of Neurovirulence of Vaccine-Derived Polioviruses

    PubMed Central

    Zhang, Yong; Yan, Dongmei; Zhu, Shuangli; Nishimura, Yorihiro; Ye, Xufang; Wang, Dongyan; Jorba, Jaume; Zhu, Hui; An, Hongqiu; Shimizu, Hiroyuki; Kew, Olen; Xu, Wenbo

    2015-01-01

    A poliomyelitis outbreak caused by type 1 circulating vaccine-derived polioviruses (cVDPVs) was identified in China in 2004. Six independent cVDPVs (eight isolates) could be grouped into a single cluster with pathways of divergence different from a single cVDPV progenitor, which circulated and evolved into both a highly neurovirulent lineage and a less neurovirulent lineage. They were as neurovirulent as the wild type 1 Mahoney strain, recombination was absent, and their nucleotide 480-G was identical to that of the Sabin strain. The Guizhou/China cVDPV strains shared 4 amino acid replacements in the NAg sites: 3 located at the BC loop, which may underlie the aberrant results of the ELISA intratypic differentiation (ITD) test. The complete ORF tree diverged into two main branches from a common ancestral infection estimated to have occurred in about mid-September 2003, nine months before the appearance of the VDPV case, which indicated recently evolved VDPV. Further, recombination with species C enteroviruses may indicate the presence and density of these enteroviruses in the population and prolonged virus circulation in the community. The aforementioned cVDPVs has important implications in the global initiative to eradicate polio: high quality surveillance permitted earliest detection and response. PMID:26603565

  19. Extensive myelitis after oral polio vaccination: MRI features.

    PubMed

    Kozic, D; Turkulov, V; Bjelan, M; Petrovic, K; Popovic-Petrovic, S; Vanhoenacker, F M

    2014-01-01

    A 7-year-old boy presented with fever and ataxia 20 days after oral polio vaccination. Magnetic resonance imaging showed extensive myelitis, involving both anterior and posterior horns of the gray matter. Complete posttreatment recovery was evident. Postvaccinal myelitis after oral polio vaccination, of either infectious or immune mediated etiology, is very rare entity that should be promptly recognized in order to initiate adequate treatment. PMID:25786294

  20. Massive outbreak of poliomyelitis caused by type-3 wild poliovirus in Angola in 1999.

    PubMed Central

    Valente, F.; Otten, M.; Balbina, F.; Van de Weerdt, R.; Chezzi, C.; Eriki, P.; Van-Dúnnen, J.; Bele, J. M.

    2000-01-01

    The largest outbreak of poliomyelitis ever recorded in Africa (1093 cases) occurred from 1 March to 28 May 1999 in Luanda, Angola, and in surrounding areas. The outbreak was caused primarily by a type-3 wild poliovirus, although type-1 wild poliovirus was circulating in the outbreak area at the same time. Infected individuals ranged in age from 2 months to 22 years; 788 individuals (72%) were younger than 3 years. Of the 590 individuals whose vaccination status was known, 23% had received no vaccine and 54% had received fewer than three doses of oral poliovirus vaccine (OPV). The major factors that contributed to this outbreak were as follows: massive displacement of unvaccinated persons to urban settings; low routine OPV coverage; inaccessible populations during the previous three national immunization days (NIDs); and inadequate sanitation. This outbreak indicates the urgent need to improve accessibility to all children during NIDs and the dramatic impact that war can have by displacing persons and impeding access to routine immunizations. The period immediately after an outbreak provides an enhanced opportunity to eradicate poliomyelitis. If continuous access in all districts for acute flaccid paralysis surveillance and supplemental immunizations cannot be assured, the current war in Angola may threaten global poliomyelitis eradication. PMID:10812730

  1. Oral Cholera Vaccine Coverage, Barriers to Vaccination, and Adverse Events following Vaccination, Haiti, 20131

    PubMed Central

    François, Jeannot; Wannemuehler, Kathleen; Iyengar, Preetha; Dismer, Amber; Adrien, Paul; Hyde, Terri B.; Marston, Barbara J.; Date, Kashmira; Mintz, Eric; Katz, Mark A.

    2015-01-01

    In 2013, the first government-led oral cholera vaccination (OCV) campaign in Haiti was implemented in Petite Anse and Cerca Carvajal. To evaluate vaccination coverage, barriers to vaccination, and adverse events following vaccination, we conducted a cluster survey. We enrolled 1,121 persons from Petite Anse and 809 persons from Cerca Carvajal, categorized by 3 age groups (1–4, 5–14, >15 years). Two-dose OCV coverage was 62.5% in Petite Anse and 76.8% in Cerca Carvajal. Two-dose coverage was lowest among persons >15 years of age. In Cerca Carvajal, coverage was significantly lower for male than female respondents (69% vs. 85%; p<0.001). No major adverse events were reported. The main reason for nonvaccination was absence during the campaign. Vaccination coverage after this campaign was acceptable and comparable to that resulting from campaigns implemented by nongovernmental organizations. Future campaigns should be tailored to reach adults who are not available during daytime hours. PMID:25988350

  2. Oral Cholera Vaccine Coverage, Barriers to Vaccination, and Adverse Events following Vaccination, Haiti, 2013(1).

    PubMed

    Tohme, Rania A; François, Jeannot; Wannemuehler, Kathleen; Iyengar, Preetha; Dismer, Amber; Adrien, Paul; Hyde, Terri B; Marston, Barbara J; Date, Kashmira; Mintz, Eric; Katz, Mark A

    2015-06-01

    In 2013, the first government-led oral cholera vaccination (OCV) campaign in Haiti was implemented in Petite Anse and Cerca Carvajal. To evaluate vaccination coverage, barriers to vaccination, and adverse events following vaccination, we conducted a cluster survey. We enrolled 1,121 persons from Petite Anse and 809 persons from Cerca Carvajal, categorized by 3 age groups (1-4, 5-14, >15 years). Two-dose OCV coverage was 62.5% in Petite Anse and 76.8% in Cerca Carvajal. Two-dose coverage was lowest among persons >15 years of age. In Cerca Carvajal, coverage was significantly lower for male than female respondents (69% vs. 85%; p<0.001). No major adverse events were reported. The main reason for nonvaccination was absence during the campaign. Vaccination coverage after this campaign was acceptable and comparable to that resulting from campaigns implemented by nongovernmental organizations. Future campaigns should be tailored to reach adults who are not available during daytime hours. PMID:25988350

  3. Immunogenicity and reactogenicity of the human rotavirus vaccine, RIX4414 oral suspension, when co-administered with routine childhood vaccines in Chinese infants.

    PubMed

    Li, Rong-Cheng; Huang, Teng; Li, Yanping; Wang, Lao-Hong; Tao, Junhui; Fu, Botao; Si, Guoai; Nong, Yi; Mo, Zhaojun; Liao, XueYan; Luan, Ivy; Tang, Haiwen; Rathi, Niraj; Karkada, Naveen; Han, Htay Htay

    2016-03-01

    This study evaluated the immunogenicity of the human rotavirus (RV) vaccine (RIX4414) when co-administered with routine childhood vaccines in Chinese infants (NCT01171963). Healthy infants aged 6-16 weeks received 2 doses of either RIX4414 or placebo according to a 0, 1-month schedule. Infants received routine diphtheria-tetanus-acellular pertussis (DTPa) and oral poliovirus (OPV) vaccines either separately from or concomitantly with RIX4414/placebo (separate and co-administration cohorts, respectively). Anti-RV IgA seroconversion rates (one month post-dose-2) and seropositivity rates (at one year of age) were measured using ELISA. Immune responses against the DTPa and OPV antigens were measured one month post-DTPa dose-3 in the co-administration cohort. Solicited local and general symptoms were recorded for 8-days post-vaccination (total cohort). The according-to-protocol immunogenicity population included 511 infants in the separate cohort and 275 in the co-administration cohort. One month post-RIX4414 dose-2, anti-RV IgA seroconversion rates were 74.7% (95% confidence interval [CI]: 68.9-79.9) and 64.2% (95% CI: 55.4-72.3) in the separate and co-administration cohorts; seropositivity rates at one year of age were 71.5% (95% CI: 65.5-77.1) and 50.0% (95% CI: 40.9-59.1), respectively. One month post-DTPa dose-3, all infants in the co-administration cohort were seroprotected against diphtheria and tetanus, and seropositive for pertussis toxoid, pertactin and filamentous haemaglutinin. Two months post-OPV dose-3, seroprotection rates against anti-poliovirus types 1, 2 and 3 were >99% in the co-administration cohort. Reactogenicity profiles were similar in both cohorts. RIX4414 was immunogenic and well-tolerated in Chinese infants and did not appear to interfere with the immunogenicity and reactogenicity of co-administered routine childhood vaccines. PMID:27149266

  4. Immunogenicity and reactogenicity of the human rotavirus vaccine, RIX4414 oral suspension, when co-administered with routine childhood vaccines in Chinese infants

    PubMed Central

    Li, Rong-cheng; Huang, Teng; Li, Yanping; Wang, Lao-Hong; Tao, Junhui; Fu, Botao; Si, Guoai; Nong, Yi; Mo, Zhaojun; Liao, XueYan; Luan, Ivy; Tang, Haiwen; Rathi, Niraj; Karkada, Naveen; Han, Htay Htay

    2016-01-01

    Abstract This study evaluated the immunogenicity of the human rotavirus (RV) vaccine (RIX4414) when co-administered with routine childhood vaccines in Chinese infants (NCT01171963). Healthy infants aged 6–16 weeks received 2 doses of either RIX4414 or placebo according to a 0, 1-month schedule. Infants received routine diphtheria-tetanus-acellular pertussis (DTPa) and oral poliovirus (OPV) vaccines either separately from or concomitantly with RIX4414/placebo (separate and co-administration cohorts, respectively). Anti-RV IgA seroconversion rates (one month post-dose-2) and seropositivity rates (at one year of age) were measured using ELISA. Immune responses against the DTPa and OPV antigens were measured one month post-DTPa dose-3 in the co-administration cohort. Solicited local and general symptoms were recorded for 8-days post-vaccination (total cohort). The according-to-protocol immunogenicity population included 511 infants in the separate cohort and 275 in the co-administration cohort. One month post-RIX4414 dose-2, anti-RV IgA seroconversion rates were 74.7% (95% confidence interval [CI]: 68.9–79.9) and 64.2% (95% CI: 55.4–72.3) in the separate and co-administration cohorts; seropositivity rates at one year of age were 71.5% (95% CI: 65.5–77.1) and 50.0% (95% CI: 40.9–59.1), respectively. One month post-DTPa dose-3, all infants in the co-administration cohort were seroprotected against diphtheria and tetanus, and seropositive for pertussis toxoid, pertactin and filamentous haemaglutinin. Two months post-OPV dose-3, seroprotection rates against anti-poliovirus types 1, 2 and 3 were >99% in the co-administration cohort. Reactogenicity profiles were similar in both cohorts. RIX4414 was immunogenic and well-tolerated in Chinese infants and did not appear to interfere with the immunogenicity and reactogenicity of co-administered routine childhood vaccines. PMID:27149266

  5. Development and consideration of global policies for managing the future risks of poliovirus outbreaks: insights and lessons learned through modeling.

    PubMed

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J; Pallansch, Mark A; Kew, Olen M; Sutter, Roland W; Aylward, R Bruce; Watkins, Margaret; Gary, Howard; Alexander, James P; Venczel, Linda; Johnson, Denise; Cáceres, Victor M; Sangrujee, Nalinee; Jafari, Hamid; Cochi, Stephen L

    2006-12-01

    The success of the Global Polio Eradication Initiative promises to bring large benefits, including sustained improvements in quality of life (i.e., cases of paralytic disease and deaths avoided) and costs saved from cessation of vaccination. Obtaining and maintaining these benefits requires that policymakers manage the transition from the current massive use of oral poliovirus vaccine (OPV) to a world without OPV and free of the risks of potential future reintroductions of live polioviruses. This article describes the analytical journey that began in 2001 with a retrospective case study on polio risk management and led to development of dynamic integrated risk, economic, and decision analysis tools to inform global policies for managing the risks of polio. This analytical journey has provided several key insights and lessons learned that will be useful to future analysts involved in similar complex decision-making processes. PMID:17184398

  6. Interactions of Cryptosporidium parvum, Giardia lamblia, Vaccinal Poliovirus Type 1, and Bacteriophages φX174 and MS2 with a Drinking Water Biofilm and a Wastewater Biofilm▿

    PubMed Central

    Helmi, Karim; Skraber, Sylvain; Gantzer, Christophe; Willame, Raphaël; Hoffmann, Lucien; Cauchie, Henry-Michel

    2008-01-01

    Biofilms colonizing surfaces inside drinking water distribution networks may provide a habitat and shelter to pathogenic viruses and parasites. If released from biofilms, these pathogens may disseminate in the water distribution system and cause waterborne diseases. Our study aimed to investigate the interactions of protozoan parasites (Cryptosporidium parvum and Giardia lamblia [oo]cysts) and viruses (vaccinal poliovirus type 1, φX174, and MS2) with two contrasting biofilms. First, attachment, persistence, and detachment of the protozoan parasites and the viruses were assessed with a drinking water biofilm. This biofilm was allowed to develop inside a rotating annular reactor fed with tap water for 7 months prior to the inoculation. Our results show that viable parasites and infectious viruses attached to the drinking water biofilm within 1 h and persisted within the biofilm. Indeed, infectious viruses were detected in the drinking water biofilm up to 6 days after the inoculation, while viral genome and viable parasites were still detected at day 34, corresponding to the last day of the monitoring period. Since viral genome was detected much longer than infectious particles, our results raise the question of the significance of detecting viral genomes in biofilms. A transfer of viable parasites and viruses from the biofilm to the water phase was observed after the flow velocity was increased but also with a constant laminar flow rate. Similar results regarding parasite and virus attachment and detachment were obtained using a treated wastewater biofilm, suggesting that our observations might be extrapolated to a wide range of environmental biofilms and confirming that biofilms can be considered a potential secondary source of contamination. PMID:18281435

  7. Oral vaccination of raccoons (Procyon lotor) with genetically modified rabies virus vaccines

    PubMed Central

    Blanton, Jesse D.; Self, Joshua; Niezgoda, Michael; Faber, Marie-Luise; Dietzschold, Bernhard; Rupprecht, Charles

    2007-01-01

    Oral vaccination is an important tool currently in use to control the spread of rabies in wildlife populations in various programs around the world. Oral rabies vaccination (ORV) of raccoons represents the largest targeted program to control wildlife rabies in the United States. Currently, the vaccinia-rabies glycoprotein recombinant virus vaccine (V-RG) is the only licensed oral rabies vaccine in the US. In the current study, captive raccoons were used to evaluate two previously described constructs of a rabies virus vaccine developed by reverse genetics (SPBNGAS and SPBNGAS-GAS) for immunogenicity and efficacy compared to the V-RG vaccine. Four of five control animals succumbed to rabies virus after severe challenge, while three of five animals vaccinated orally with SPBNGAS succumbed. No mortality was observed for animals administered SPBNGAS-GAS or the V-RG vaccine. The results of this preliminary study suggest that SPBNGAS-GAS provides comparable efficacy to V-RG. Additional studies will be needed to determine the duration of immunity and optimal dosage of SPBNGAS-GAS and to examine its efficacy in other reservoir species. PMID:17826874

  8. Oral vaccination of raccoons (Procyon lotor) with genetically modified rabies virus vaccines.

    PubMed

    Blanton, Jesse D; Self, Joshua; Niezgoda, Michael; Faber, Marie-Luise; Dietzschold, Bernhard; Rupprecht, Charles

    2007-10-16

    Oral vaccination is an important tool currently in use to control the spread of rabies in wildlife populations in various programs around the world. Oral rabies vaccination (ORV) of raccoons represents the largest targeted program to control wildlife rabies in the United States. Currently, the vaccinia-rabies glycoprotein recombinant virus vaccine (V-RG) is the only licensed oral rabies vaccine in the US. In the current study, captive raccoons were used to evaluate two previously described constructs of a rabies virus vaccine developed by reverse genetics (SPBNGAS and SPBNGAS-GAS) for immunogenicity and efficacy compared to the V-RG vaccine. Four of five control animals succumbed to rabies virus after severe challenge, while three of five animals vaccinated orally with SPBNGAS succumbed. No mortality was observed for animals administered SPBNGAS-GAS or the V-RG vaccine. The results of this preliminary study suggest that SPBNGAS-GAS provides comparable efficacy to V-RG. Additional studies will be needed to determine the duration of immunity and optimal dosage of SPBNGAS-GAS and to examine its efficacy in other reservoir species. PMID:17826874

  9. Oral Immunization of Mice with Killed Salmonella typhimurium Vaccine

    PubMed Central

    Waldman, Robert H.; Grunspan, Ruth; Ganguly, Rama

    1972-01-01

    A study was undertaken to assess the efficacy of oral, parenteral, and intraperitoneal immunization methods of administering killed Salmonella typhimurium vaccine to mice and to evaluate the effectiveness of single and multiple doses of the vaccine containing varied numbers of the killed bacteria. A further objective of this study was to evaluate the effect of adding substances to the vaccine to which have been ascribed “adjuvant” properties. The protection was estimated by isolation of bacteria from the spleen and feces after oral challenge of the mice with live S. typhimurium. The results showed that one or more doses of 1010 organisms given orally led to significant protection. This rate of protection increased proportionately with the number of doses up to 10 doses, which offered 100% protection. Streptomycin, when added to multiple doses of 109 or more organisms given orally, increased the degree of protection, but beryllium sulfate and pertussis vaccine did not. Although multiple doses afforded similar systemic protection by all three routes of immunization, oral immunization yielded significantly greater local protection than that observed after subcutaneous or intraperitoneal immunization. PMID:4564152

  10. [Evaluation of an experimental rabies vaccine by the oral and intestinal route with inactivated vaccines, concentrated or non-concentrated].

    PubMed

    Atanasiu, P; Metianu, T; Bolanos, A

    1982-01-01

    Application of beta-propiolactone inactivated rabies vaccine prepared in bovine embryo kidney cells, concentrated or non concentrated, by intestinal or oral route resulted in antibody production in rats and cats. 80-100% of vaccinated rats were protected against challenge with street rabies virus. The same vaccines (lyophilized in gelatin capsules) stimulated antibody production in more than 50% (5/8) cats which received the vaccine by the oral route. PMID:7128069

  11. New developments in oral vaccines and mucosal adjuvants.

    PubMed

    Subiza, Jose L; El-Qutob, David; Fernandez-Caldas, Enrique

    2015-01-01

    Mucosal immunity is the first line of defence of the organism against several pathogens and, at the same time, it is of critical importance in allergic diseases. Oral vaccines have been developed with the aim of enhancing the immune response to pathogens and for the treatment of allergic diseases. One of the major issues concerning oral vaccines is the use of oral adjuvants which could facilitate antigen presentation with the consequent induction of an effective immune response. The present review consists of an analysis, point by point, of the different patents that have been presented in the last 12 months in the different agencies: European (EP), US, and World Intellectual Property Organization (WIPO) and a general analysis of the future developments and trends in this emerging area. PMID:25669205

  12. Oral cholera vaccine--for whom, when, and why?

    PubMed

    Topps, Maureen H

    2006-01-01

    The search for a safe, effective, well tolerated, low cost vaccine against the ancient cholera enemy has been ongoing since the 19th century and has been revitalized in the past two decades since the advent of recombinant technology. Large-scale field trials have readily demonstrated the tolerability and safety of oral cholera vaccine in various forms. Variable levels of protection have been shown and one challenge has been to demonstrate whether this is a cost effective treatment in differing environments including its use in endemic and epidemic areas as well as for travelers. A review of recent literature was undertaken to assess the effectiveness and uses of currently available oral cholera vaccine. While the evidence does not support the creation of formal guidelines, some clear recommendations can be made. There is undoubtedly the potential to reduce the burden of illness both in endemic and epidemic situations. For travelers, certain higher risk groups may benefit from protection against cholera. More significantly, the short term cross-protection afforded by whole cell, B subunit (WC BS) oral cholera vaccine formulations against enterotoxigenic E. coli, (ETEC), the commonest causative agent of traveler's diarrhoea, may prove to be the most important raison d'être. PMID:16887724

  13. History of polio vaccination

    PubMed Central

    Baicus, Anda

    2012-01-01

    Poliomyelitis is an acute paralytic disease caused by three poliovirus (PV) serotypes. Less than 1% of PV infections result in acute flaccid paralysis. The disease was controlled using the formalin-inactivated Salk polio vaccine (IPV) and the Sabin oral polio vaccine (OPV). Global poliomyelitis eradication was proposed in 1988 by the World Health Organization to its member states. The strategic plan established the activities required for polio eradication, certification for regions, OPV cessation phase and post-OPV phase. OPV is the vaccine of choice for the poliomyelitis eradication program because it induces both a systemic and mucosal immune response. The major risks of OPV vaccination are the appearance of Vaccine-Associated Paralytic Poliomyelitis cases (VAPP) and the emergence of Vaccine Derived Polioviruses strains. The supplementary immunization with monovalent strains of OPV type 1 or type 3 or with a new bivalent oral polio vaccine bOPV (containing type 1 and type 3 PV) has been introduced in those regions where the virus has been difficult to control. Most countries have switched the schedule of vaccination by using IPV instead of OPV because it poses no risk of vaccine-related disease. Until 2008, poliomyelitis was controlled in Romania, an Eastern European country, predominantly using OPV. The alternative vaccination schedule (IPV/OPV) was implemented starting in September 2008, while beginning in 2009, the vaccination was IPV only. The risk of VAPP will disappear worldwide with the cessation of use of OPV. The immunization for polio must be maintained for at least 5 to 10 years using IPV. PMID:24175215

  14. Poliovirus Laboratory Based Surveillance: An Overview.

    PubMed

    Zaidi, Syed Sohail Zahoor; Asghar, Humayun; Sharif, Salmaan; Alam, Muhammad Masroor

    2016-01-01

    World Health Assembly (WHA) in 1988 encouraged the member states to launch Global Polio Eradication Initiative (GPEI) (resolution WHA41.28) against "the Crippler" called poliovirus, through strong routine immunization program and intensified surveillance systems. Since its launch, global incidence of poliomyelitis has been reduced by more than 99 % and the disease squeezed to only three endemic countries (Afghanistan, Pakistan, and Nigeria) out of 125. Today, poliomyelitis is on the verge of eradication, and their etiological agents, the three poliovirus serotypes, are on the brink of extinction from the natural environment. The last case of poliomyelitis due to wild type 2 strain occurred in 1999 in Uttar Pradesh, India whereas the last paralytic case due to wild poliovirus type 3 (WPV3) was seen in November, 2012 in Yobe, Nigeria. Despite this progress, undetected circulation cannot fully rule out the eradication as most of the poliovirus infections are entirely subclinical; hence sophisticated environmental surveillance is needed to ensure the complete eradication of virus. Moreover, the vaccine virus in under-immunized communities can sometimes revert and attain wild type characteristics posing a big challenge to the program. PMID:26983728

  15. In-Depth Characterization of Live Vaccines Used in Europe for Oral Rabies Vaccination of Wildlife.

    PubMed

    Cliquet, Florence; Picard-Meyer, Evelyne; Mojzis, Miroslav; Dirbakova, Zuzana; Muizniece, Zita; Jaceviciene, Ingrida; Mutinelli, Franco; Matulova, Marta; Frolichova, Jitka; Rychlik, Ivan; Celer, Vladimir

    2015-01-01

    Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD) strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release. PMID:26509266

  16. In-Depth Characterization of Live Vaccines Used in Europe for Oral Rabies Vaccination of Wildlife

    PubMed Central

    Cliquet, Florence; Picard-Meyer, Evelyne; Mojzis, Miroslav; Dirbakova, Zuzana; Muizniece, Zita; Jaceviciene, Ingrida; Mutinelli, Franco; Matulova, Marta; Frolichova, Jitka; Rychlik, Ivan; Celer, Vladimir

    2015-01-01

    Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD) strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release. PMID:26509266

  17. Antibody Secreting Cell Responses following Vaccination with Bivalent Oral Cholera Vaccine among Haitian Adults

    PubMed Central

    Charles, Richelle C.; Mayo-Smith, Leslie M.; Teng, Jessica E.; Xu, Peng; Kováč, Pavol; Ryan, Edward T.; Qadri, Firdausi; Franke, Molly F.; Ivers, Louise C.; Harris, Jason B.

    2016-01-01

    Background The bivalent whole-cell (BivWC) oral cholera vaccine (Shanchol) is effective in preventing cholera. However, evaluations of immune responses following vaccination with BivWC have been limited. To determine whether BivWC induces significant mucosal immune responses, we measured V. cholerae O1 antigen-specific antibody secreting cell (ASC) responses following vaccination. Methodology/Principal Findings We enrolled 24 Haitian adults in this study, and administered doses of oral BivWC vaccine 14 days apart (day 0 and day 14). We drew blood at baseline, and 7 days following each vaccine dose (day 7 and 21). Peripheral blood mononuclear cells (PBMCs) were isolated, and ASCs were enumerated using an ELISPOT assay. Significant increases in Ogawa (6.9 cells per million PBMCs) and Inaba (9.5 cells per million PBMCs) OSP-specific IgA ASCs were detected 7 days following the first dose (P < 0.001), but not the second dose. The magnitude of V. cholerae-specific ASC responses did not appear to be associated with recent exposure to cholera. ASC responses measured against the whole lipolysaccharide (LPS) antigen and the OSP moiety of LPS were equivalent, suggesting that all or nearly all of the LPS response targets the OSP moiety. Conclusions/Significance Immunization with the BivWC oral cholera vaccine induced ASC responses among a cohort of healthy adults in Haiti after a single dose. The second dose of vaccine resulted in minimal ASC responses over baseline, suggesting that the current dosing schedule may not be optimal for boosting mucosal immune responses to V. cholerae antigens for adults in a cholera-endemic area. PMID:27308825

  18. Oral vaccination of mice against tetanus with recombinant Lactococcus lactis.

    PubMed

    Robinson, K; Chamberlain, L M; Schofield, K M; Wells, J M; Le Page, R W

    1997-07-01

    To determine whether a protective immune response could be elicited by oral delivery of a recombinant bacterial vaccine, tetanus toxin fragment C (TTFC) was expressed constitutively in Lactococcus lactis and administered orally to C57 BL/6 mice. The antibody titers elicited were lower than those following intranasal immunization (a route already known to result in high-level systemic anti-TTFC immune responses) but the protective efficacy was the same order of magnitude. The serum antibody isotypes elicited were predominantly IgG1 and IgG2a. TTFC-specific fecal IgA responses could be detected following oral or intranasal immunization. Chemically killed lactococci administered via the intranasal route were also able to elicit serum antibody responses of similar levels and kinetics to those induced by live bacteria. PMID:9219268

  19. Assessment of cell culture and polymerase chain reaction procedures for the detection of polioviruses in wastewater.

    PubMed Central

    Grabow, W. O.; Botma, K. L.; de Villiers, J. C.; Clay, C. G.; Erasmus, B.

    1999-01-01

    WHO considers that environmental surveillance for wild-type polioviruses is potentially important for surveillance for acute flaccid paralysis as a means of confirming eradication of poliomyelitis. The present study investigated methods for detecting polioviruses in a variety of water environments in South Africa. Most polioviruses were isolated on L20B mouse cells, which, however, were not selective: 16 reoviruses and 8 enteroviruses, apparently animal strains, were also isolated on these cells. Vaccine strains of polioviruses were isolated from surface waters during and shortly after two rounds of mass vaccination of children in an informal settlement where there was no sewerage. The results demonstrated the feasibility of poliovirus surveillance in such settlements. It was also evident that neither poliovirus vaccine strains nor other viruses were likely to interfere significantly with the detection of wild-type polioviruses. Optimal isolation of polioviruses was accomplished by parallel inoculation of L20B mouse cells and at least the PLC/PRF/5 human liver and buffalo green monkey (BGM) kidney cell lines. Analysis of cell cultures using the polymerase chain reaction revealed that 319 test samples contained at least 263 human enteroviruses that failed to produce a cytopathogenic effect. This type of analysis thus significantly increased the sensitivity of enterovirus detection. PMID:10680244

  20. Vaccination of full-sib channel catfish families against enteric septicemia of catfish with an oral live attenuated Edwardsiella ictaluri vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The study evaluated the efficacy of an oral live-attenuated Edwardsiella ictaluri vaccine against enteric septicemia of catfish in 20 full-sib fingerling channel catfish families. Each family was split into vaccinated and non-vaccinated groups. The vaccine was delivered orally by feeding fish diet...

  1. The case for periodic OPV routine vaccination campaigns.

    PubMed

    Houy, Nicolas

    2016-01-21

    The possibility of periodic routine vaccination campaigns (PRVCs) is introduced in the context of a search for optimal oral poliovirus vaccine (OPV) administration strategies. Like the usual continuous routine vaccination campaign (CRVC), PRVCs target only newborns. However, they are not necessarily implemented continuously in time. Using a dynamic and compartmental polio transmission model in a stochastic context, it is shown that some PRVCs can achieve much greater efficiency than CRVC in terms of probability of wild poliovirus (WPV) eradication, even though they never outperform CRVC in terms of total number of paralytic infections. Moreover, these PRVCs results can be obtained at a lower price than CRVC. It is also shown that, even though PRVCs do not perform better than pulse vaccination campaigns (PVCs) when only epidemiological outputs are valued, they can do so when a cost-benefit analysis is preferred. PMID:26523796

  2. Experimental oral polio vaccines and acquired immune deficiency syndrome.

    PubMed

    Hooper, E

    2001-06-29

    The simian immunodeficiency virus (SIV) of the common chimpanzee is widely acknowledged as the direct ancestor of HIV-1. There is increasing historical evidence that during the late 1950s, kidneys were routinely excised from central African chimpanzees by scientists who were collaborating with the polio vaccine research of Dr Hilary Koprowski, and sent - inter alia - to vaccine-making laboratories in the USA and Africa, and to unspecified destinations in Belgium. While there is no direct evidence that cells from these kidneys were used as a substrate for growing Dr Koprowski's oral polio vaccines, there is a startling coincidence between places in Africa where his CHAT vaccine was fed, and the first appearances in the world of HIV-1 group M and group-M-related AIDS. Because of the enormous implications of the hypothesis that AIDS may be an unintended iatrogenic (physician-caused) disease, it is almost inevitable that this theory will engender heated opposition from many of those in the scientific establishment, and those with vested interests. PMID:11405924

  3. Evaluation of novel oral vaccine candidates and validation of a caprine model of Johne's disease

    PubMed Central

    Hines, Murray E.; Turnquist, Sue E.; Ilha, Marcia R. S.; Rajeev, Sreekumari; Jones, Arthur L.; Whittington, Lisa; Bannantine, John P.; Barletta, Raúl G.; Gröhn, Yrjö T.; Katani, Robab; Talaat, Adel M.; Li, Lingling; Kapur, Vivek

    2014-01-01

    Johne's disease (JD) caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a major threat to the dairy industry and possibly some cases of Crohn's disease in humans. A MAP vaccine that reduced of clinical disease and/or reduced fecal shedding would aid in the control of JD. The objectives of this study were (1) to evaluate the efficacy of 5 attenuated strains of MAP as vaccine candidates compared to a commercial control vaccine using the protocol proposed by the Johne's Disease Integrated Program (JDIP) Animal Model Standardization Committee (AMSC), and (2) to validate the AMSC Johne's disease goat challenge model. Eighty goat kids were vaccinated orally twice at 8 and 10 weeks of age with an experimental vaccine or once subcutaneously at 8 weeks with Silirum® (Zoetis), or a sham control oral vaccine at 8 and 10 weeks. Kids were challenged orally with a total of approximately 1.44 × 109 CFU divided in two consecutive daily doses using MAP ATCC-700535 (K10-like bovine isolate). All kids were necropsied at 13 months post-challenge. Results indicated that the AMSC goat challenge model is a highly efficient and valid model for JD challenge studies. None of the experimental or control vaccines evaluated prevented MAP infection or eliminated fecal shedding, although the 329 vaccine lowered the incidence of infection, fecal shedding, tissue colonization and reduced lesion scores, but less than the control vaccine. Based on our results the relative performance ranking of the experimental live-attenuated vaccines evaluated, the 329 vaccine was the best performer, followed by the 318 vaccine, then 316 vaccine, 315 vaccine and finally the 319 vaccine was the worst performer. The subcutaneously injected control vaccine outperformed the orally-delivered mutant vaccine candidates. Two vaccines (329 and 318) do reduce presence of JD gross and microscopic lesions, slow progression of disease, and one vaccine (329) reduced fecal shedding and tissue colonization. PMID

  4. Seroepidemiology of Polioviruses among University Students in Northern Italy

    PubMed Central

    Baldo, Vincenzo; Cocchio, Silvia; Lazzari, Roberta; Saracino, Elena; Bertoncello, Chiara; Buja, Alessandra; Trevisan, Andrea

    2012-01-01

    The widespread use of poliovirus vaccination schemes has led to a marked decline in the incidence of paralytic poliomyelitis worldwide, but wild poliovirus is still endemic in some developing countries, and in 2009 a total of 23 countries reported at least 1 case of poliomyelitis caused by wild-strain polio viruses. A serological survey was thus conducted on the immunological status against polioviruses of 318 young adults, classified by their country of origin. Immunity to poliomyelitis was assessed by neutralizing antibody titration in tissues cultured on microplates. The rate of seronegativity (≤1:8) in the study population was 26.7% for poliovirus type 1, 7.2% for type 2, and 22.6% for type 3. In our sample of 318 individuals, 219 (68.9%) were Italian and 99 (31.1%) were from outside the European Union (EU). The proportion of cases found seropositive to polioviruses 1 and 3 decreased significantly with older age; this age-related decrease was more evident in the Italian group than among the non-EU subjects. Any risk of the wild virus recurring and causing paralytic poliomyelitis must be prevented, keeping Europe polio free by means of appropriate immunological protection, until polio has been conclusively eradicated all over the world. Judging from our findings, it may be worth considering administering a fifth dose of polio vaccine to adolescents. PMID:22739695

  5. Seroepidemiology of polioviruses among university students in northern Italy.

    PubMed

    Baldo, Vincenzo; Baldovin, Tatjana; Cocchio, Silvia; Lazzari, Roberta; Saracino, Elena; Bertoncello, Chiara; Buja, Alessandra; Trevisan, Andrea

    2012-08-01

    The widespread use of poliovirus vaccination schemes has led to a marked decline in the incidence of paralytic poliomyelitis worldwide, but wild poliovirus is still endemic in some developing countries, and in 2009 a total of 23 countries reported at least 1 case of poliomyelitis caused by wild-strain polio viruses. A serological survey was thus conducted on the immunological status against polioviruses of 318 young adults, classified by their country of origin. Immunity to poliomyelitis was assessed by neutralizing antibody titration in tissues cultured on microplates. The rate of seronegativity (≤ 1:8) in the study population was 26.7% for poliovirus type 1, 7.2% for type 2, and 22.6% for type 3. In our sample of 318 individuals, 219 (68.9%) were Italian and 99 (31.1%) were from outside the European Union (EU). The proportion of cases found seropositive to polioviruses 1 and 3 decreased significantly with older age; this age-related decrease was more evident in the Italian group than among the non-EU subjects. Any risk of the wild virus recurring and causing paralytic poliomyelitis must be prevented, keeping Europe polio free by means of appropriate immunological protection, until polio has been conclusively eradicated all over the world. Judging from our findings, it may be worth considering administering a fifth dose of polio vaccine to adolescents. PMID:22739695

  6. Real-time Polymerase Chain Reaction Analysis of Sewage Samples to Determine Oral Polio Vaccine Circulation Duration and Mutation After Mexican National Immunization Weeks

    PubMed Central

    Troy, Stephanie B.; Ferreyra-Reyes, Leticia; Canizales-Quintero, Sergio; Huang, ChunHong; Lee, Yu-Jin; Báez-Saldaña, Renata; Ferreira-Guerrero, Elizabeth; García-García, Lourdes; Maldonado, Yvonne

    2012-01-01

    Background. Oral polio vaccine (OPV) can mutate and cause outbreaks of paralytic poliomyelitis with prolonged replication. After poliovirus eradication, global use of inactivated polio vaccine (IPV) may be needed until all OPV stops circulating. Mexico, where children receive routine IPV but where OPV is given only during biannual national immunization weeks (NIWs), provides a natural setting to study duration of OPV circulation in a community primarily vaccinated with IPV. Methods. One-liter sewage samples from four separate arroyos (creeks) near Orizaba, Mexico, were collected monthly for 12 months. Concentrated sewage underwent RNA extraction, reverse transcription, and real-time polymerase chain reaction (PCR) to detect OPV serotypes 1, 2, and 3 and their variants containing the serotype-specific point mutation in the 5′ untranslated region associated with neurovirulence. Results. OPV was detected 3, 4, 5, and 7 months after the May 2010 NIW, but was not detected at 6 or 8 months. A second and third NIW occurred in February 2011 and May 2011, and OPV was detected in the sewage monthly after both of these NIW through July 2011 when collection stopped. The OPV detected was primarily serotype 2 and predominantly contained the point mutations in the 5′ untranslated region associated with increased neurovirulence. Conclusions. OPV was detected in sewage as late as 7 months after an NIW in a Mexican community primarily vaccinated with IPV, but was not detected at 8 months, suggesting that OPV circulation may have ceased. These data suggest that in communities with high vaccination rates, 1 or 2 years of IPV administration after OPV cessation could be sufficient to prevent outbreaks of paralytic poliomyelitis from vaccine-derived strains. PMID:23667738

  7. Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes.

    PubMed

    Buddle, Bryce M; Denis, Michel; Aldwell, Frank E; Martin Vordermeier, H; Glyn Hewinson, R; Neil Wedlock, D

    2008-11-01

    Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine delivered to calves by the subcutaneous (s.c.) or by the oral route in a formulated lipid matrix has been previously shown to induce similar levels of protection against bovine tuberculosis. The current study was aimed at determining whether a combination of delivering BCG by s.c. and oral routes would enhance levels of protection, compared to only one route of vaccination. Forty calves were randomly divided into four groups (10/group). Calves were vaccinated with 10(6)colony forming units (CFU) of BCG Pasteur by the s.c. route or orally with 10(9)CFU BCG incorporated into a lipid formulation. One group received a combination of BCG administered by both the s.c. and oral routes and a non-vaccinated group served as a control. The two groups of calves that received s.c. BCG produced strong IFN-gamma responses in whole blood cultures stimulated with bovine purified protein derivative (PPD) 3 weeks after vaccination. Cattle vaccinated just with oral BCG in a lipid matrix produced a strong IFN-gamma response 8 weeks after vaccination, and peaking at 11 weeks after vaccination. All calves were challenged by the intratracheal route with M. bovis 15 weeks after vaccination and were euthanized and necropsied to assess protection at 17 weeks following challenge. BCG given s.c. or orally induced significant and comparable levels of protection against the virulent challenge. Vaccination of cattle by a combination of s.c./oral routes did not enhance protection beyond that achieved by s.c. or oral vaccination alone. We conclude that vaccination of cattle with BCG by a combination of routes has no beneficial additive effects, compared to a single s.c. administration of BCG or BCG given orally in a lipid formulation. PMID:18439875

  8. Comparative efficacy of intranasal and oral vaccines against Bordetella bronchiseptica in dogs.

    PubMed

    Ellis, J A; Gow, S P; Waldner, C L; Shields, S; Wappel, S; Bowers, A; Lacoste, S; Xu, Z; Ball, E

    2016-06-01

    In order to determine the comparative efficacy of vaccines administered intranasally or orally to protect puppies from disease subsequent to experimental infection with Bordetella bronchiseptica (Bb), a randomized controlled trial was performed using 48 approximately 8-week-old specific pathogen free, Bb naive Beagle puppies. Puppies were randomized into three groups and administered vaccines containing Bb intranasally or orally, or a placebo intranasally. Twenty-one days later, all dogs were challenge exposed via aerosol administration of Bb. Clinical signs, nasal bacterial shedding and immune responses were monitored for 28 days after challenge. Intranasally vaccinated puppies had significantly lower rates of coughing, nasal discharge, retching and sneezing (i.e. were less sick clinically) than control puppies. The distinction between the orally vaccinated puppies and the control puppies was less consistent. The orally vaccinated puppies had less coughing and less retching than the control puppies, but nasal discharge and sneezing did not differ from control animals. Orally vaccinated puppies had higher rates of coughing, nasal discharge, retching and sneezing than the intranasally vaccinated puppies. Although both intranasal and oral Bb vaccines stimulated immune responses associated with disease sparing following Bb infection, the intranasal route of delivery conferred superior clinical outcomes. The observed difference in clinical efficacy suggests the need to question the rationale for the use of currently available orally administered Bb vaccines. PMID:27256028

  9. Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe.

    PubMed

    Müller, Thomas F; Schröder, Ronald; Wysocki, Patrick; Mettenleiter, Thomas C; Freuling, Conrad M

    2015-01-01

    In Europe, the elimination of wildlife rabies using oral rabies vaccination [ORV] of foxes for more than 30 years has been a success story. Since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across Europe has not been available yet, we evaluated the use of different vaccine baits over the entire period of ORV [1978-2014]. Our findings provide valuable insights into the complexity of ORV programs in terms of vaccine related issues. More than 10 oral vaccines against rabies were used over the past four decades. Depending on many factors, the extent to which oral rabies virus vaccines were used varied considerably resulting in huge differences in the number of vaccine doses disseminated in ORV campaigns as well as in large spatial and temporal overlaps. Although vaccine virus strains derived from the SAD rabies virus isolate were the most widely used, the success of ORV campaigns in Europe cannot be assigned to a single oral rabies virus vaccine alone. Rather, the successful elimination of fox rabies is the result of an interaction of different key components of ORV campaigns, i.e. vaccine strain, vaccine bait and strategy of distribution. PMID:26280895

  10. Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe

    PubMed Central

    Müller, Thomas F.; Schröder, Ronald; Wysocki, Patrick; Mettenleiter, Thomas C.; Freuling, Conrad M.

    2015-01-01

    In Europe, the elimination of wildlife rabies using oral rabies vaccination [ORV] of foxes for more than 30 years has been a success story. Since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across Europe has not been available yet, we evaluated the use of different vaccine baits over the entire period of ORV [1978–2014]. Our findings provide valuable insights into the complexity of ORV programs in terms of vaccine related issues. More than 10 oral vaccines against rabies were used over the past four decades. Depending on many factors, the extent to which oral rabies virus vaccines were used varied considerably resulting in huge differences in the number of vaccine doses disseminated in ORV campaigns as well as in large spatial and temporal overlaps. Although vaccine virus strains derived from the SAD rabies virus isolate were the most widely used, the success of ORV campaigns in Europe cannot be assigned to a single oral rabies virus vaccine alone. Rather, the successful elimination of fox rabies is the result of an interaction of different key components of ORV campaigns, i.e. vaccine strain, vaccine bait and strategy of distribution. PMID:26280895

  11. Development of an oral vaccine for immunisation of rainbow trout (Oncorhynchus mykiss) against viral haemorrhagic septicaemia.

    PubMed

    Adelmann, Malte; Köllner, Bernd; Bergmann, Sven M; Fischer, Uwe; Lange, Bodo; Weitschies, Werner; Enzmann, Peter-Joachim; Fichtner, Dieter

    2008-02-01

    In the European Union Viral Haemorrhagic Septicaemia (VHS) eradication is still based on stamping out. Due to the lack of effective low cost vaccines immune prophylaxis is currently not used to combat VHS. This paper describes a new oral delivery method for immunisation of trout with attenuated virus. The vaccine consists of lyophilised virus surrounded by polyethylene glycol (PEG) and was extruded under low temperature. In the stomach of trout, the use of additional neutralising and adsorbing bases resulted in a neutral pH around the vaccine pellets, thus protecting the antigen against gastric acid. The in vivo efficacy of this delivery method was examined in three animal challenge experiments using an attenuated VHS virus (VHSV) strain as a vaccine. After vaccination, VHSV mRNA in gut, heart, kidney, spleen and blood was amplified by semi-nested PCR after RT-PCR. Indirect immune fluorescence test detected VHS vaccine virus in the gut. The expression of MHC class II, CD4 and CD8alpha mRNAs after oral vaccination was measured in gut using real-time RT-PCR. Antibody levels were measured by ELISA one week before vaccination and five weeks after vaccination. Animals were challenged six weeks after vaccination with highly virulent VHSV and mortality was recorded. The experiments showed that orally delivered vaccine virus was released from the vaccine preparation, penetrated the gut mucosa and led to higher expression levels of MHC class II and CD4 mRNAs when compared to control guts. VHSV antibodies were detected after oral vaccination. Immunisation with this new vaccine formulation was followed by a significant protection against VHSV. While the cumulative mortality in the non-vaccinated control group reached 70%, more than 75% of the orally vaccinated fish were protected upon challenge. PMID:18191880

  12. Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies.

    PubMed

    Wang, Shujing; Liu, Huiqin; Zhang, Xinyi; Qian, Feng

    2015-07-01

    Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations. PMID:25944045

  13. Delivery of immunogens to mucosal immune system using an oral inactivated cholera vaccine: a new approach for development of oral vaccines.

    PubMed

    Azizi, Ali; Ghunaim, Haitham; Sirskyj, Danylo; Fallahi, Firouzeh; Le, Hoang Thanh; Kumar, Ashok

    2013-07-01

    Oral vaccines have several attractive features; however, due to several challenges, to date, only a limited number of oral vaccines are licensed. Over the past two decades, several oral vehicle delivery systems have been developed to address these challenges and deliver antigens to the target cells in the mucosal immune system. While the size of vehicle delivery systems, the quantity of components in the vehicle formulation, the dose of administration, and even the type of animals species, are important aspects in development of a suitable oral vaccine, our results showed that entrapment of inactivated Vibrio cholera, a component in the structure of Dukoral vaccine into oral vehicle delivery systems, is able to induce a more rigorous humoral immune response in the systemic compartment. We further investigated the mechanism of Dukoral vaccine as a potential stimulator in induction of immune response by immunizing TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. We are hopeful that these findings will lead to development of more precisely-designed oral vaccines in the future. PMID:23466688

  14. Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs

    PubMed Central

    Wang, Zhao; Ruan, Juncheng; Tang, Lijun; Jia, Ziming; Cui, Min; Zhao, Ling; Fu, Zhen F.

    2015-01-01

    Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs. PMID:26436700

  15. Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs.

    PubMed

    Zhou, Ming; Wang, Lei; Zhou, Songqin; Wang, Zhao; Ruan, Juncheng; Tang, Lijun; Jia, Ziming; Cui, Min; Zhao, Ling; Fu, Zhen F

    2015-11-17

    Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs. PMID:26436700

  16. Introduction of sequential inactivated polio vaccine-oral polio vaccine schedule for routine infant immunization in Brazil's National Immunization Program.

    PubMed

    Domingues, Carla Magda Allan S; de Fátima Pereira, Sirlene; Cunha Marreiros, Ana Carolina; Menezes, Nair; Flannery, Brendan

    2014-11-01

    In August 2012, the Brazilian Ministry of Health introduced inactivated polio vaccine (IPV) as part of sequential polio vaccination schedule for all infants beginning their primary vaccination series. The revised childhood immunization schedule included 2 doses of IPV at 2 and 4 months of age followed by 2 doses of oral polio vaccine (OPV) at 6 and 15 months of age. One annual national polio immunization day was maintained to provide OPV to all children aged 6 to 59 months. The decision to introduce IPV was based on preventing rare cases of vaccine-associated paralytic polio, financially sustaining IPV introduction, ensuring equitable access to IPV, and preparing for future OPV cessation following global eradication. Introducing IPV during a national multivaccination campaign led to rapid uptake, despite challenges with local vaccine supply due to high wastage rates. Continuous monitoring is required to achieve high coverage with the sequential polio vaccine schedule. PMID:25316829

  17. Mass Vaccination with a New, Less Expensive Oral Cholera Vaccine Using Public Health Infrastructure in India: The Odisha Model

    PubMed Central

    Kar, Shantanu K.; Sah, Binod; Patnaik, Bikash; Kim, Yang Hee; Kerketta, Anna S.; Shin, Sunheang; Rath, Shyam Bandhu; Ali, Mohammad; Mogasale, Vittal; Khuntia, Hemant K.; Bhattachan, Anuj; You, Young Ae; Puri, Mahesh K.; Lopez, Anna Lena; Maskery, Brian; Nair, Gopinath B.; Clemens, John D.; Wierzba, Thomas F.

    2014-01-01

    Introduction The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model. Methods All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel. Results The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25

  18. Immune responses and resistance to brucellosis in mice vaccinated orally with Brucella abortus RB51.

    PubMed Central

    Stevens, M G; Olsen, S C; Palmer, M V; Pugh, G W

    1996-01-01

    Immune responses and resistance to infection with Brucella abortus 2308 (S2308) were measured in mice following oral or intraperitoneal (i.p.) vaccination with strain RB51 (SRB51). Bacteria persisted in the parotid lymph node for 4 weeks following oral vaccination of mice with 5 x 10(8) or 5 x 10(6) CFU of SRB51. Bacteria did not appear in the spleen during 12 weeks after oral vaccination, whereas they did appear in the spleen for 8 weeks following i.p. vaccination of mice with SRB51 (5 x 10(8) or 5 x 10(6) CFU). Increased resistance to S2308 infection occurred at 12 to 20 weeks in mice vaccinated i.p. with SRB51 (5 x 10(8) or 5 x 10(6) CFU) but occurred at 12 weeks only in mice vaccinated orally with SRB51 (5 x 10(8) CFU). Oral SRB51 vaccination induced lower levels of antibodies to the surface antigens of intact SRB51 bacteria than did i.p. vaccination. However, neither route of vaccination induced anamnestic antibody responses to the surface antigens of intact S2308 bacteria after challenge infection of the vaccinated mice with S2308. Mice vaccinated orally with SRB51 and challenged with S2308 at 12 to 20 weeks had lower and less persistent spleen cell proliferation and production of gamma interferon in response to S2308 and certain immunodominant S2308 proteins (32 to < or = 18 kDa) than did mice vaccinated i.p. with SRB51. However, mice vaccinated orally or i.p. with SRB51 and challenged with S2308 had similar spleen cell tumor necrosis factor alpha production. These results indicate that oral vaccination of mice with SRB51 was effective in inducing protective immunity to S2308 infection, although the immunity was lower and less persistent than that induced by i.p. vaccination. The lower protective immunity induced by oral vaccination may have resulted from lower and less persistent cell-mediated immunity and gamma interferon production in response to S2308 and S2308 proteins. PMID:8890203

  19. Large intestine-targeted nanoparticle-releasing oral vaccine to control genitorectal viral infection

    PubMed Central

    Zhu, Qing; Talton, James; Zhang, Guofeng; Cunningham, Tshaka; Wang, Zijian; Waters, Robert C.; Kirk, James; Eppler, Bärbel; Dennis M, Klinman; Sui, Yongjun; Gagnon, Susan; Belyakov, Igor M.; Mumper, Russell J.; Berzofsky, Jay A.

    2012-01-01

    Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both mucosal sites in animal studies, can be achieved successfully by direct intra-colorectal (i.c.r.) administration, which is, however, clinically impractical. Oral delivery seems preferable, but risks vaccine destruction in the upper gastrointestinal tract. Therefore, we designed a large intestine-targeted oral delivery with pH-dependent microparticles containing vaccine nanoparticles, which induced colorectal immunity in mice comparably to colorectal vaccination and protected against rectal or vaginal viral challenge. Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system. Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible novel strategy for immune protection of rectal and vaginal mucosa. PMID:22797811

  20. An Estimation of Private Household Costs to Receive Free Oral Cholera Vaccine in Odisha, India

    PubMed Central

    Mogasale, Vittal; Kar, Shantanu K.; Kim, Jong-Hoon; Mogasale, Vijayalaxmi V.; Kerketta, Anna S.; Patnaik, Bikash; Rath, Shyam Bandhu; Puri, Mahesh K.; You, Young Ae; Khuntia, Hemant K.; Maskery, Brian; Wierzba, Thomas F.; Sah, Binod

    2015-01-01

    Background Service provider costs for vaccine delivery have been well documented; however, vaccine recipients’ costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India. Methods Following a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire-based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha. Findings On average, families were located 282.7 (SD = 254.5) meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs. Interpretation The private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines. PMID:26352143

  1. Impact of the sequential IPV/OPV schedule on vaccination coverage levels--United States, 1997.

    PubMed

    1998-12-01

    In January 1997, the Advisory Committee on Immunization Practices (ACIP) recommended adoption of a sequential inactivated poliovirus vaccine (IPV)-oral poliovirus vaccine (OPV) vaccination schedule. The schedule of injections of IPV at 2 months and 4 months of age, followed by OPV at 12-18 months and again at 4-6 years was intended to minimize the risk for vaccine-associated paralytic poliomyelitis (VAPP) while maintaining population immunity to the potential introduction of wild-type poliovirus. To determine whether this change may result in reduced or delayed vaccination coverage because parents or physicians might be reluctant to administer multiple injections at a single visit, CDC investigated the impact of the change to a sequential IPV-OPV vaccination schedule at two large West coast health maintenance organizations (HMOs). This report summarizes the results of the investigation and indicates that changing to an initial two doses of IPV was not associated with decreases in vaccination coverage levels of routinely recommended vaccinations. PMID:9853937

  2. Human Papillomavirus Vaccine Intention among College Men: What's Oral Sex Got to Do with It?

    ERIC Educational Resources Information Center

    Crosby, Richard A.; DiClemente, Ralph J.; Salazar, Laura F.; Nash, Rachel; Younge, Sinead; Head, Sara

    2012-01-01

    Objective: To identify associations between engaging in oral sex and perceived risk of oral cancer among college men. Also, to identify associations, and their moderating factors, between oral sex and human papillomavirus (HPV) vaccine acceptance. Methods: Young men were recruited from 2 university campuses in the South (N = 150). Men completed an…

  3. Combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b vaccine; Infanrix™ hexa

    PubMed Central

    Baldo, Vincenzo; Bonanni, Paolo; Castro, Marcela; Gabutti, Giovanni; Franco, Elisabetta; Marchetti, Federico; Prato, Rosa; Vitale, Francesco

    2014-01-01

    Infant vaccination using 2-dose priming at 3 and 5 mo of age with a booster at 11–12 mo of age was pioneered in Italy. The 3-5-11 schedule is now used in a growing number of European countries. Infanrix™ hexa (DTPa-HBV-IPV/Hib, GlaxoSmithKline Vaccines) was first licensed for use in 2000 and has been the only pediatric hexavalent vaccine available since 2005. We reviewed available clinical trial data describing the immunogenicity of DTPa-HBV-IPV/Hib when administered at 3, 5, and 11 mo of age, and conducted an analysis of safety using global and Italian post-marketing surveillance data. In Italy, DTPa-HBV-IPV/Hib has a demonstrated safety record extending over a decade of use, it has been associated with record levels of vaccine coverage, and with sustained disease control in vaccinated cohorts. Hexavalent vaccines will continue to contribute to high vaccine coverage in Italy and across Europe. PMID:24004825

  4. Use of Rhodamine B as a biomarker for oral plague vaccination of prairie dogs

    USGS Publications Warehouse

    Fernandez, Julia Rodriguez-Ramos; Rocke, Tonie E.

    2011-01-01

    Oral vaccination against Yersinia pestis could provide a feasible approach for controlling plague in prairie dogs (Cynomys spp.) for conservation and public health purposes. Biomarkers are useful in wildlife vaccination programs to demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential biomarker for oral plague vaccination because it allows nonlethal sampling of animals through hair, blood, and feces. We found that RB is an appropriate marker for bait uptake studies of C. ludovicianus) when used at concentrations <0.5% of bait mass dosed to deliver >10 mg RB per kg target animal mass. Whiskers with follicles provided the best sample for RB detection.

  5. Influence of oral sex and oral cancer information on young adults' oral sexual-risk cognitions and likelihood of HPV vaccination.

    PubMed

    Stock, Michelle L; Peterson, Laurel M; Houlihan, Amy E; Walsh, Laura A

    2013-01-01

    Public health information and educational interventions regarding human papillomavirus (HPV) have focused on the link between vaginal sex and cervical cancer among women. Many people are unaware that HPV can be transmitted through oral sex or that HPV causes oral cancers. Given that HPV infections and unprotected oral sex are increasing, research on oral sex-related HPV risk is important. This study examined the effect of a brief informational intervention regarding HPV and oral sex on the sexual risk cognitions of young adults. College students (N = 238) read information on HPV, oral sex, and oral cancer or no information. Participants then completed measures of oral sex and HPV knowledge, oral sex willingness, HPV vaccination likelihood, and risk perceptions. Participants who read the information on HPV and oral sex and cancer (compared to those who did not) reported greater knowledge, perceived risk and concern, and lower willingness to engage in oral sex. These effects were only significant among women. However, men reported a higher likelihood of future HPV vaccination compared to women who had not yet received the vaccine. Focusing on oral sex and cancer, this study adds to research investigating ways to reduce HPV infections. PMID:22236342

  6. Assessment of the efficacy of oral vaccination of livestock guardian dogs in the framework of oral rabies vaccination of wild canids in Israel.

    PubMed

    Yakobson, B A; King, R; Sheichat, N; Eventov, B; David, D

    2008-01-01

    Since 1956, red foxes (Vulpes vulpes) and golden jackals (Canis aureus) have been the primary vectors maintaining wildlife rabies in Israel. Oral rabies vaccination of wild canids, initiated in 1998, resulted in near-elimination of the disease in wildlife by 2005. In 2005 and 2006, an outbreak of rabies was observed in stray dogs in the vaccinated area of the Golan Heights, with no cases in foxes or jackals. Epidemiological investigations showed that the infected dogs were from territories across the border. This was confirmed by molecular analysis, which showed that the virus was different from rabies isolates endemic to this area. The objective of this study was to determine bait acceptance and the feasibility of oral rabies vaccination in packs of livestock guardian dogs. Coated sachets and fishmeal polymer baits of Raboral V-RG (Merial, USA) were tested in five different test zones. Both formats were hand-fed to individual dogs and to dogs belonging to dog packs. Bait uptake and consumption were observed in each dog. The estimated efficacy of oral rabies vaccination was very low (a maximum of 28%). Vaccine delivery problems were observed in dogs belonging to packs, whereby dominant animals consumed multiple baits and in competitive situations baits were swallowed whole. The uncertainty of oral vaccination necessitated turning to other methods to control this outbreak: stray dogs were removed and herd dogs were vaccinated parenterally. This study showed that oral rabies vaccination of dogs in packs using baits designed for wildlife would not be effective. Possibly, different baits or steps to circumvent competition within the pack will make this approach feasible. PMID:18634475

  7. Experimental induction and oral transmission of avian AA amyloidosis in vaccinated white hens.

    PubMed

    Murakami, Tomoaki; Muhammad, Naeem; Inoshima, Yasuo; Yanai, Tokuma; Goryo, Masanobu; Ishiguro, Naotaka

    2013-06-01

    Avian AA amyloidosis is commonly observed in adult birds afflicted with bacterial infections or chronic inflammatory disorders. Experimental AA amyloidosis in birds can be induced by repeated inflammatory stimulation, such as injection with casein or vaccination with oil-emulsified bacterins. However, the transmission of amyloidosis among avian species has not been studied well to date. In the present study, we confirm the potential induction of avian AA amyloidosis by inoculation of Salmonella enteritidis (SE) vaccine or Mycoplasma gallisepticum vaccine. To determine the transmission of chicken AA amyloidosis among white hens, we induced experimental AA amyloidosis in vaccinated chickens by intravenous or oral administration of chicken AA fibrils. Amyloid deposits were observed in chickens injected with SE and inoculated with chicken AA fibrils intravenously (21/26: 81%) and orally (8/12: 67%). These results suggest that chicken AA amyloidosis can be induced by vaccinations, and may be transmitted among like species by oral administration. PMID:23548152

  8. Stability of vaccinia-vectored recombinant oral rabies vaccine under field conditions: A 3-year study

    PubMed Central

    Hermann, Joseph R.; Fry, Alethea M.; Siev, David; Slate, Dennis; Lewis, Charles; Gatewood, Donna M.

    2011-01-01

    Rabies is an incurable zoonotic disease caused by rabies virus, a member of the rhabdovirus family. It is transmitted through the bite of an infected animal. Control methods, including oral rabies vaccination (ORV) programs, have led to a reduction in the spread and prevalence of the disease in wildlife. This study evaluated the stability of RABORAL, a recombinant vaccinia virus vaccine that is used in oral rabies vaccination programs. The vaccine was studied in various field microenvironments in order to describe its viability and facilitate effective baiting strategies. Field microenvironments influenced the stability of this vaccine in this study. This study emphasizes the importance of understanding how vaccines perform under varying field conditions in order to plan effective baiting strategies. PMID:22468025

  9. Comparison of oral and intramuscular recombinant canine distemper vaccination in African wild dogs (Lycaon pictus).

    PubMed

    Connolly, Maren; Thomas, Patrick; Woodroffe, Rosie; Raphael, Bonnie L

    2013-12-01

    A series of three doses of recombinant canary-pox-vectored canine distemper virus vaccine was administered at 1-mo intervals, orally (n = 8) or intramuscularly (n = 13), to 21 previously unvaccinated juvenile African wild dogs (Lycaon pictus) at the Wildlife Conservation Society's Bronx Zoo. Titers were measured by serum neutralization at each vaccination and at intervals over a period of 3.5-21.5 mo after the initial vaccination. All postvaccination titers were negative for orally vaccinated animals at all sampling time points. Of the animals that received intramuscular vaccinations, 100% had presumed protective titers by the end of the course of vaccination, but only 50% of those sampled at 6.5 mo postvaccination had positive titers. None of the three animals sampled at 21.5 mo postvaccination had positive titers. PMID:24450046

  10. Oral rabies vaccination in north america: opportunities, complexities, and challenges.

    PubMed

    Slate, Dennis; Algeo, Timothy P; Nelson, Kathleen M; Chipman, Richard B; Donovan, Dennis; Blanton, Jesse D; Niezgoda, Michael; Rupprecht, Charles E

    2009-01-01

    Steps to facilitate inter-jurisdictional collaboration nationally and continentally have been critical for implementing and conducting coordinated wildlife rabies management programs that rely heavily on oral rabies vaccination (ORV). Formation of a national rabies management team has been pivotal for coordinated ORV programs in the United States of America. The signing of the North American Rabies Management Plan extended a collaborative framework for coordination of surveillance, control, and research in border areas among Canada, Mexico, and the US. Advances in enhanced surveillance have facilitated sampling of greater scope and intensity near ORV zones for improved rabies management decision-making in real time. The value of enhanced surveillance as a complement to public health surveillance was best illustrated in Ohio during 2007, where 19 rabies cases were detected that were critical for the formulation of focused contingency actions for controlling rabies in this strategically key area. Diverse complexities and challenges are commonplace when applying ORV to control rabies in wild meso-carnivores. Nevertheless, intervention has resulted in notable successes, including the elimination of an arctic fox (Vulpes lagopus) rabies virus variant in most of southern Ontario, Canada, with ancillary benefits of elimination extending into Quebec and the northeastern US. Progress continues with ORV toward preventing the spread and working toward elimination of a unique variant of gray fox (Urocyon cinereoargenteus) rabies in west central Texas. Elimination of rabies in coyotes (Canis latrans) through ORV contributed to the US being declared free of canine rabies in 2007. Raccoon (Procyon lotor) rabies control continues to present the greatest challenges among meso-carnivore rabies reservoirs, yet to date intervention has prevented this variant from gaining a broad geographic foothold beyond ORV zones designed to prevent its spread from the eastern US. Progress continues

  11. Post-licensure deployment of oral cholera vaccines: a systematic review

    PubMed Central

    Martin, Stephen; Lopez, Anna Lena; Bellos, Anna; Ali, Mohammad; Alberti, Kathryn; Anh, Dang Duc; Costa, Alejandro; Grais, Rebecca F; Legros, Dominique; Luquero, Francisco J; Ghai, Megan B; Perea, William; Sack, David A

    2014-01-01

    Abstract Objective To describe and analyse the characteristics of oral cholera vaccination campaigns; including location, target population, logistics, vaccine coverage and delivery costs. Methods We searched PubMed, the World Health Organization (WHO) website and the Cochrane database with no date or language restrictions. We contacted public health personnel, experts in the field and in ministries of health and did targeted web searches. Findings A total of 33 documents were included in the analysis. One country, Viet Nam, incorporates oral cholera vaccination into its public health programme and has administered approximately 10.9 million vaccine doses between 1997 and 2012. In addition, over 3 million doses of the two WHO pre-qualified oral cholera vaccines have been administered in more than 16 campaigns around the world between 1997 and 2014. These campaigns have either been pre-emptive or reactive and have taken place under diverse conditions, such as in refugee camps or natural disasters. Estimated two-dose coverage ranged from 46 to 88% of the target population. Approximate delivery cost per fully immunized person ranged from 0.11–3.99 United States dollars. Conclusion Experience with oral cholera vaccination campaigns continues to increase. Public health officials may draw on this experience and conduct oral cholera vaccination campaigns more frequently. PMID:25552772

  12. An orally administered DNA vaccine targeting vascular endothelial growth factor receptor-3 inhibits lung carcinoma growth.

    PubMed

    Chen, Yan; Liu, Xin; Jin, Cong Guo; Zhou, Yong Chun; Navab, Roya; Jakobsen, Kristine Raaby; Chen, Xiao Qun; Li, Jia; Li, Ting Ting; Luo, Lu; Wang, Xi Cai

    2016-02-01

    Lung cancer is the leading cause of mortality and 5-year survival rate is very low worldwide. Recent studies show that vascular endothelial growth factor receptor-3 (VEGFR-3) signaling pathway contributes to lung cancer progression. So we hypothesize that an oral DNA vaccine that targets VEGFR-3 carried by attenuated Salmonella enterica serovar typhimurium strain SL3261 has impacts on lung cancer progression. In this study, the oral VEGFR-3-based vaccine-immunized mice showed appreciable inhibition of tumor growth and tumor lymphatic microvessels in lung cancer mice model. Moreover, the oral VEGFR-3-based vaccine-immunized mice showed remarkable increases in both VEGFR-3-specific antibody levels and cytotoxic activity. Furthermore, the oral VEGFR-3-based vaccine-immunized mice showed a significant increase in the levels of T helper type 1 (Th1) cell intracellular cytokine expression (IL-2, IFN-γ, and TNF-α). After inoculation with murine Lewis lung carcinoma (LLC) cells, CD4(+) or CD8(+) T cell numbers obviously declined in control groups whereas high levels were maintained in the oral VEGFR-3-based vaccine group. These results demonstrated that the oral VEGFR-3-based vaccine could induce specific humoral and cellular immune responses and then significantly inhibit lung carcinoma growth via suppressing lymphangiogenesis. PMID:26376999

  13. Oral Vaccination With Vaccinia Virus Expressing the Tick Antigen Subolesin Inhibits Tick Feeding and Transmission of Borrelia burgdorferi Vaccination

    PubMed Central

    Bensaci, Mekki; Bhattacharya, Debaditya; Clark, Roger; Hu, Linden T.

    2014-01-01

    Immunization with the Ixodes scapularis protein, subolesin, has previously been shown to protect hosts against tick infestation and to decrease acquisition of Anaplsma marginale and Babesia bigemina. Here we report the efficacy of subolesin expressed from Vaccinia virus for use as an orally delivered reservoir–targeted vaccine for prevention of tick infestation and acquisition/transmission of Borrelia burgdorferi to its tick and mouse hosts. We cloned subolesin into Vaccinia virus and showed that it is expressed from mammalian cells infected with the recombinant virus in vitro. We then vaccinated mice by oral gavage. A single dose of the vaccine was sufficient for mice to generate antibody response to subolesin. Vaccination with the subolesin expressing Vaccinia virus inhibited tick infestation by 52% compared to control vaccination with Vaccinia virus and reduced uptake of B. burgdorferi among the surviving ticks that fed to repletion by 34%. There was a reduction in transmission of B. burgdorferi to uninfected vaccinated mice of 40% compared to controls. These results suggest that subolesin has potential as a component of a reservoir targeted vaccine to decrease B. burgdorferi, Babesia and Anaplasma species infections in their natural hosts. PMID:22864146

  14. Oral vaccination and protection of red foxes (Vulpes vulpes) against rabies using ONRAB, an adenovirus-rabies recombinant vaccine.

    PubMed

    Brown, L J; Rosatte, R C; Fehlner-Gardiner, C; Bachmann, P; Ellison, J A; Jackson, F R; Taylor, J S; Davies, C; Donovan, D

    2014-02-12

    Twenty-seven red foxes (Vulpes vulpes) were each offered a bait containing ONRAB, a recombinant oral rabies vaccine that uses a human adenovirus vector to express the immunogenic rabies virus glycoprotein; 10 controls received no vaccine baits. Serum samples collected from all foxes before treatment, and each week post-treatment for 16 weeks, were tested for the presence of rabies virus neutralizing antibody (RVNA). In the bait group, a fox was considered a responder to vaccination if serum samples from 3 or more consecutive weeks had RVNA ≥0.5 IU/ml. Using this criterion, 79% of adult foxes (11/14) and 46% of juveniles (6/13) responded to vaccination with ONRAB. Serum RVNA of adults first tested positive (≥0.5 IU/ml) between weeks 1 and 3, about 4 weeks earlier than in juveniles. Adults also responded with higher levels of RVNA and these levels were maintained longer. Serum samples from juveniles tested positive for 1-4 consecutive weeks; in adults the range was 2-15 weeks, with almost half of adults maintaining titres above 0.5 IU/ml for 9 or more consecutive weeks. Based on the kinetics of the antibody response to ONRAB, the best time to sample sera of wild adult foxes for evidence of vaccination is 7-11 weeks following bait distribution. Thirty-four foxes (25 ONRAB, 9 controls) were challenged with vulpine street virus 547 days post-vaccination. All controls developed rabies whereas eight of 13 adult vaccinates (62%) and four of 12 juvenile vaccinates (33%) survived. All foxes classed as non-responders to vaccination developed rabies. Of foxes considered responders to vaccination, 80% of adults (8/10) and 67% of juveniles (4/6) survived challenge. The duration of immunity conferred to foxes would appear adequate for bi-annual and annual bait distribution schedules as vaccinates were challenged 1.5 years post-vaccination. PMID:24374501

  15. Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.

    PubMed

    Zhang, Lei; Zeng, Zhanzhuang; Hu, Chaohua; Bellis, Susan L; Yang, Wendi; Su, Yintao; Zhang, Xinyan; Wu, Yunkun

    2016-01-01

    Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(D,L-lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia, an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae, a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination. PMID:26624805

  16. Oral rabies vaccination variation in tetracycline biomarking among Ohio raccoons.

    PubMed

    Algeo, Timothy P; Norhenberg, Gary; Hale, Robert; Montoney, Andrew; Chipman, Richard B; Slate, Dennis

    2013-04-01

    Oral rabies vaccination (ORV) programs have traditionally relied on tetracycline marking as an index to bait uptake. Whether tetracycline serves well in this capacity depends on its deposition affinity and ability to be detected consistently among tissues selected for analysis from target species. We evaluated samples from 760 hunter-harvested raccoons (Procyon lotor) from areas in Ohio where ORV had been conducted during 1998, 1999, and 2001. Tetracycline marking was evaluated within and among first premolar (PM1), second premolar (PM2), and canine (CN) teeth, and mandibular bone (MB) by side (left versus right); and by tissue type. Tetracycline detection ranged from 6.5% in PM1 in 1998 to 56.3% in right-side MB in 2001. PM1 teeth were less frequently marked (21.7%) than PM2 (27.7%), CN (33.0%), or MB (42.0%). Tetracycline detection was similar in left and right PM1, PM2, and CN teeth, but differed in MB. Tetracycline marking was significantly different among all tissue types. PMID:23568908

  17. 77 FR 49409 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... rabies in the United States. On July 9, 2012, we published in the Federal Register (77 FR 40322- 40323... Animal and Plant Health Inspection Service Oral Rabies Vaccine Trial; Availability of an Environmental... with the proposed field trial to test the safety and efficacy of an experimental oral rabies...

  18. Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study

    PubMed Central

    Ivers, Louise C; Hilaire, Isabelle J; Teng, Jessica E; Almazor, Charles P; Jerome, J Gregory; Ternier, Ralph; Boncy, Jacques; Buteau, Josiane; Murray, Megan B; Harris, Jason B; Franke, Molly F

    2015-01-01

    Background Between April and June 2012, a reactive cholera vaccination campaign was conducted in Haiti using an oral inactivated bivalent whole-cell vaccine (BivWC). Methods We conducted a case-control study to estimate field effectiveness of the vaccine. Cases had acute watery diarrhea, sought treatment at one of three participating cholera treatment units from October 24, 2012 through March 9, 2014, and had a stool sample positive for cholera by culture. For each case, four controls (individuals who did not seek treatment for acute watery diarrhea) were matched by location of residence, calendar time, and age. We also conducted a bias-indicator case-control study to assess the likelihood of bias in the vaccine effectiveness (VE) study. Findings During the study period, 114 eligible individuals presented with acute watery diarrhea and were enrolled. 47 were analyzed as cases in the VE case-control study and 42 as cases in the bias-indicator study. In multivariable analyses, VE was 63% [95% confidence interval (CI): 8%–85%] by self-reported vaccination and 58% [95% CI: 13%–80%] for verified vaccination. Neither self-reported nor verified vaccination was significantly associated with non-cholera diarrhea (VE: 18% [95% CI: −208%–−78%] by self-report and −21% [95%CI: −238%–57%] for verified vaccination). Interpretation BivWC oral cholera vaccine was effective in protecting against cholera in Haiti during the study period –from 4 through 24 months after vaccination. Vaccination is an important component of epidemic cholera control efforts. Funding National Institutes of Health, Delivering Oral Vaccines Effectively project, Department of Global Health and Social Medicine at Harvard Medical School. PMID:25701994

  19. Pregnancy Outcomes after a Mass Vaccination Campaign with an Oral Cholera Vaccine in Guinea: A Retrospective Cohort Study

    PubMed Central

    Grout, Lise; Martinez-Pino, Isabel; Ciglenecki, Iza; Keita, Sakoba; Diallo, Alpha Amadou; Traore, Balla; Delamou, Daloka; Toure, Oumar; Nicholas, Sarala; Rusch, Barbara; Staderini, Nelly; Serafini, Micaela; Grais, Rebecca F.; Luquero, Francisco J.

    2015-01-01

    Introduction Since 2010, WHO has recommended oral cholera vaccines as an additional strategy for cholera control. During a cholera episode, pregnant women are at high risk of complications, and the risk of fetal death has been reported to be 2–36%. Due to a lack of safety data, pregnant women have been excluded from most cholera vaccination campaigns. In 2012, reactive campaigns using the bivalent killed whole-cell oral cholera vaccine (BivWC), included all people living in the targeted areas aged ≥1 year regardless of pregnancy status, were implemented in Guinea. We aimed to determine whether there was a difference in pregnancy outcomes between vaccinated and non-vaccinated pregnant women. Methods and Findings From 11 November to 4 December 2013, we conducted a retrospective cohort study in Boffa prefecture among women who were pregnant in 2012 during or after the vaccination campaign. The primary outcome was pregnancy loss, as reported by the mother, and fetal malformations, after clinical examination. Primary exposure was the intake of the BivWC vaccine (Shanchol) during pregnancy, as determined by a vaccination card or oral history. We compared the risk of pregnancy loss between vaccinated and non-vaccinated women through binomial regression analysis. A total of 2,494 pregnancies were included in the analysis. The crude incidence of pregnancy loss was 3.7% (95%CI 2.7–4.8) for fetuses exposed to BivWC vaccine and 2.6% (0.7–4.5) for non-exposed fetuses. The incidence of malformation was 0.6% (0.1–1.0) and 1.2% (0.0–2.5) in BivWC-exposed and non-exposed fetuses, respectively. In both crude and adjusted analyses, fetal exposure to BivWC was not significantly associated with pregnancy loss (adjusted risk ratio (aRR = 1.09 [95%CI: 0.5–2.25], p = 0.818) or malformations (aRR = 0.50 [95%CI: 0.13–1.91], p = 0.314). Conclusions In this large retrospective cohort study, we found no association between fetal exposure to BivWC and risk of pregnancy loss or

  20. Oral administration of myostatin-specific recombinant Saccharomyces cerevisiae vaccine in rabbit.

    PubMed

    Liu, Zhongtian; Zhou, Gang; Ren, Chonghua; Xu, Kun; Yan, Qiang; Li, Xinyi; Zhang, Tingting; Zhang, Zhiying

    2016-04-29

    Yeast is considered as a simple and cost-effective host for protein expression, and our previous studies have proved that Saccharomyces cerevisiae can deliver recombinant protein and DNA into mouse dendritic cells and can further induce immune responses as novel vaccines. In order to know whether similar immune responses can be induced in rabbit by oral administration of such recombinant S. cerevisiae vaccine, we orally fed the rabbits with heat-inactivated myostatin-recombinant S. cerevisiae for 5 weeks, and then myostatin-specific antibody in serum was detected successfully by western blotting and ELISA assay. The rabbits treated with myostatin-recombinant S. cerevisiae vaccine grew faster and their muscles were much heavier than that of the control group. As a common experimental animal and a meat livestock with great economic value, rabbit was proved to be the second animal species that have been successfully orally immunized by recombinant S. cerevisiae vaccine after mice. PMID:27005809

  1. Oral vaccination against Helicobacter pylori infection is not effective in mice with Fas ligand deficiency.

    PubMed

    Avitzur, Yaron; Galindo-Mata, Esther; Jones, Nicola L

    2005-12-01

    The aim of this study was to delineate the role of the Fas pathway in vaccination against Helicobacter pylori. C57BL/6 and Fas ligand-deficient (gld) mice were divided into 3 groups: control, H. pylori infected, and orally vaccinated (H. pylori whole cell sonicate and cholera toxin adjuvant). Oral vaccination prevented H. pylori colonization in 78% of C57BL/6 mice compared to only 18% of gld mice. Vaccination did not alter the degree of apoptosis in either strain of mice. Vaccination led to significant increase in interleukin (IL)-5 and IL-10 in C57BL/6 but not gld mice. H. pylori infection increased interferon (IFN)-gamma levels in C57BL/6 but not in gld mice while vaccination had no effect on IFN-gamma levels in either strain. Oral vaccination is not effective in Fas ligand-deficient mice likely owing to lack of effective cytokine responses. This indicates that the Fas pathway plays a critical role in promoting an appropriate effector response following H. pylori vaccination. PMID:16416178

  2. First Outbreak Response Using an Oral Cholera Vaccine in Africa: Vaccine Coverage, Acceptability and Surveillance of Adverse Events, Guinea, 2012

    PubMed Central

    Luquero, Francisco J.; Grout, Lise; Ciglenecki, Iza; Sakoba, Keita; Traore, Bala; Heile, Melat; Dialo, Alpha Amadou; Itama, Christian; Serafini, Micaela; Legros, Dominique; Grais, Rebecca F.

    2013-01-01

    Background Despite World Health Organization (WHO) prequalification of two safe and effective oral cholera vaccines (OCV), concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières organized the first mass vaccination campaign using a two-dose OCV (Shanchol) as an additional control measure to respond to the on-going nationwide epidemic. Overall, 316,250 vaccines were delivered. Here, we present the results of vaccination coverage, acceptability and surveillance of adverse events. Methodology/Principal Findings We performed a cross-sectional cluster survey and implemented adverse event surveillance. The study population included individuals older than 12 months, eligible for vaccination, and residing in the areas targeted for vaccination (Forécariah and Boffa, Guinea). Data sources were household interviews with verification by vaccination card and notifications of adverse events from surveillance at vaccination posts and health centres. In total 5,248 people were included in the survey, 3,993 in Boffa and 1,255 in Forécariah. Overall, 89.4% [95%CI:86.4–91.8%] and 87.7% [95%CI:84.2–90.6%] were vaccinated during the first round and 79.8% [95%CI:75.6–83.4%] and 82.9% [95%CI:76.6–87.7%] during the second round in Boffa and Forécariah respectively. The two dose vaccine coverage (including card and oral reporting) was 75.8% [95%CI: 71.2–75.9%] in Boffa and 75.9% [95%CI: 69.8–80.9%] in Forécariah respectively. Vaccination coverage was higher in children. The main reason for non-vaccination was absence. No severe adverse events were notified. Conclusions/Significance The well-accepted mass vaccination campaign reached high coverage in a remote area with a mobile population. Although OCV should not be foreseen as the long-term solution for global cholera control, they should be

  3. Oral vaccination reduces the incidence of tuberculosis in free-living brushtail possums

    PubMed Central

    Tompkins, D. M.; Ramsey, D. S. L.; Cross, M. L.; Aldwell, F. E.; de Lisle, G. W.; Buddle, B. M.

    2009-01-01

    Bovine tuberculosis (Tb) caused by Mycobacterium bovis has proved refractory to eradication from domestic livestock in countries with wildlife disease reservoirs. Vaccination of wild hosts offers a way of controlling Tb in livestock without wildlife culling. This study was conducted in a Tb-endemic region of New Zealand, where the introduced Australian brushtail possum (Trichosurus vulpecula) is the main wildlife reservoir of Tb. Possums were trapped and vaccinated using a prototype oral-delivery system to deliver the Tb vaccine bacille Calmette–Guerin. Vaccinated and control possums were matched according to age, sex and location, re-trapped bimonthly and assessed for Tb status by palpation and lesion aspiration; the site was depopulated after 2 years and post-mortem examinations were conducted to further identify clinical Tb cases and subclinical infection. Significantly fewer culture-confirmed Tb cases were recorded in vaccinated possums (1/51) compared with control animals (12/71); the transition probability from susceptible to infected was significantly reduced in both males and females by vaccination. Vaccine efficacy was estimated at 95 per cent (87–100%) for females and 96 per cent (82–99%) for males. Hence, this trial demonstrates that orally delivered live bacterial vaccines can significantly protect wildlife against natural disease exposure, indicating that wildlife vaccination, along with existing control methods, could be used to eradicate Tb from domestic animals. PMID:19493904

  4. Co-Circulation and Evolution of Polioviruses and Species C Enteroviruses in a District of Madagascar

    PubMed Central

    Rakoto-Andrianarivelo, Mala; Guillot, Sophie; Iber, Jane; Balanant, Jean; Blondel, Bruno; Riquet, Franck; Martin, Javier; Kew, Olen; Randriamanalina, Bakolalao; Razafinimpiasa, Lalatiana; Rousset, Dominique; Delpeyroux, Francis

    2007-01-01

    Between October 2001 and April 2002, five cases of acute flaccid paralysis (AFP) associated with type 2 vaccine-derived polioviruses (VDPVs) were reported in the southern province of the Republic of Madagascar. To determine viral factors that favor the emergence of these pathogenic VDPVs, we analyzed in detail their genomic and phenotypic characteristics and compared them with co-circulating enteroviruses. These VDPVs appeared to belong to two independent recombinant lineages with sequences from the type 2 strain of the oral poliovaccine (OPV) in the 5′-half of the genome and sequences derived from unidentified species C enteroviruses (HEV-C) in the 3′-half. VDPV strains showed characteristics similar to those of wild neurovirulent viruses including neurovirulence in poliovirus-receptor transgenic mice. We looked for other VDPVs and for circulating enteroviruses in 316 stools collected from healthy children living in the small area where most of the AFP cases occurred. We found vaccine PVs, two VDPVs similar to those found in AFP cases, some echoviruses, and above all, many serotypes of coxsackie A viruses belonging to HEV-C, with substantial genetic diversity. Several coxsackie viruses A17 and A13 carried nucleotide sequences closely related to the 2C and the 3Dpol coding regions of the VDPVs, respectively. There was also evidence of multiple genetic recombination events among the HEV-C resulting in numerous recombinant genotypes. This indicates that co-circulation of HEV-C and OPV strains is associated with evolution by recombination, resulting in unexpectedly extensive viral diversity in small human populations in some tropical regions. This probably contributed to the emergence of recombinant VDPVs. These findings give further insight into viral ecosystems and the evolutionary processes that shape viral biodiversity. PMID:18085822

  5. Risk of polio reintroduction to border regions of Islamic Republic of Iran: seroprevalence study of children with at least 5 doses of oral polio vaccine.

    PubMed

    Izadi, S; Shahmahmoodi, S; Zahraei, S M; Dorostkar, F; Majdzadeh, R

    2014-05-01

    Movements of populations from countries where polio has not been eradicated is a concern in the Islamic Republic of Iran. A cross-sectional, community-based study was implemented in 2010 in 2 districts in Sistan-va-Baluchestan Province near the south-east border. The aim was to determine the seroprevalence of antibodies in children aged 20 (± 2) months who had received at least 5 doses of trivalent oral polio vaccine. Using cluster sampling, 365 children were enrolled for serological testing. Antibody titres ≥ 1:10 were considered positive. Seropositive rates for antibody against poliovirus serotypes 1, 2 and 3 were 94.1%, 96.7% and 78.3% respectively. The lowest seropositive rate was for antibody against polio serotype 3 (PV3) among boys (58.3%). Exclusive breastfeeding showed a direct relationship with antibody response to PV3 (OR = 2.0; 95% CI: 1.1-3.6). Improving community protection against PV3 is an urgent programme priority. PMID:24952285

  6. Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

    PubMed

    Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

    2011-12-15

    Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

  7. Classical swine fever virus Strain 'C'. How long is it detectable after oral vaccination?

    PubMed

    Kaden, V; Lange, E; Riebe, R; Lange, B

    2004-08-01

    To determine the persistence period of C-strain vaccine virus in immunized animals, domestic pigs and wild boars were vaccinated orally and killed on different days post vaccinationem (dpv). Tissue samples were taken at necropsy from both species for detection of C-strain virus. From domestic pigs nasal swabs and faeces were also collected. During the investigation period (2-12 dpv) vaccine virus could never be detected in nasal secretions and in faeces of vaccinated domestic pigs. In contrast, C-strain virus was found in organs until day 8 pv in domestic pigs and until day 9 pv in wild boars. Whereas in domestic pigs virus was detected in tonsils, Ln. mandibularis or in spleen, in wild boar it only was found in tonsils. We conclude that C-strain vaccine virus is not detectable in wild boars longer than 10-12 days after intake of the vaccine baits. PMID:15458487

  8. Protective oral vaccination against infectious salmon anaemia virus in Salmo salar.

    PubMed

    Caruffo, Mario; Maturana, Carlos; Kambalapally, Swetha; Larenas, Julio; Tobar, Jaime A

    2016-07-01

    Infectious salmon anemia (ISA) is a systemic disease caused by an orthomyxovirus, which has a significant economic impact on the production of Atlantic salmon (Salmo salar). Currently, there are several commercial ISA vaccines available, however, those products are applied through injection, causing stress in the fish and leaving them susceptible to infectious diseases due to the injection process and associated handling. In this study, we evaluated an oral vaccine against ISA containing a recombinant viral hemagglutinin-esterase and a fusion protein as antigens. Our findings indicated that oral vaccination is able to protect Atlantic salmon against challenge with a high-virulence Chilean isolate. The oral vaccination was also correlated with the induction of IgM-specific antibodies. On the other hand, the vaccine was unable to modulate expression of the antiviral related gene Mx, showing the importance of the humoral response to the disease survival. This study provides new insights into fish protection and immune response induced by an oral vaccine against ISA, but also promises future development of preventive solutions or validation of the current existing therapies. PMID:26994669

  9. Development of a cost-effective oral vaccination method against viral disease in fish.

    PubMed

    Companjen, A R; Florack, D E A; Bastiaans, J H M W; Matos, C I; Bosch, D; Rombout, J H W M

    2005-01-01

    Different vaccination methods have been applied to protect fish against the detrimental effects of various pathogens. Several studies have shown the potentials of oral vaccination. In theory oral vaccination is an effortless and stress-free method which can be applied at almost any age. In general, however, the vaccine has to be protected to avoid digestion, which results in high costs for application in aquaculture. In this paper we introduce a cost-effective oral vaccination strategy for viral diseases of fish. The vaccines discussed here include fusion proteins consisting of a gut adhesion molecule and a viral peptide expressed in plants. The adhesion molecule mediates binding to and uptake from the gut, whereas the viral peptide functions as vaccine antigen mediating the induction of a humoral immune response. The first pilot studies using a fusion of the gut adhesion molecule and well-characterised heterologous linear B- and T-cell viral epitopes, produced in potato tubers, showed a promising binding and subsequent uptake in the end gut of carp. The results further indicated that a specific humoral immune response was evoked. PMID:15962477

  10. Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection.

    PubMed

    Zhu, Qing; Talton, James; Zhang, Guofeng; Cunningham, Tshaka; Wang, Zijian; Waters, Robert C; Kirk, James; Eppler, Bärbel; Klinman, Dennis M; Sui, Yongjun; Gagnon, Susan; Belyakov, Igor M; Mumper, Russell J; Berzofsky, Jay A

    2012-08-01

    Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both of these mucosal sites in animal studies, can be achieved successfully by direct intracolorectal (i.c.r.) administration, but this route is clinically impractical. Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract. Therefore, we designed a large intestine-targeted oral delivery with pH-dependent microparticles containing vaccine nanoparticles, which induced colorectal immunity in mice comparably to colorectal vaccination and protected against rectal and vaginal viral challenge. Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system. Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa. PMID:22797811

  11. Global routine vaccination coverage, 2009.

    PubMed

    2010-10-29

    The widespread use of vaccines has greatly improved global public health, preventing millions of childhood hospitalizations and deaths each year. Vaccination of children also is projected to avert adult deaths through the prevention of hepatitis B (HepB) virus--related chronic liver disease and liver cancer and human papilloma virus--related cervical cancer. When the World Health Organization (WHO) began the Expanded Programme on Immunization in 1974, <5% of the world's children had been fully vaccinated with bacille Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP) vaccine, oral poliovirus vaccine, and measles-containing vaccine (MCV) during the first year of life. Since then, increased vaccination coverage has resulted in substantial reductions in morbidity and mortality, including a >99% decline in polio incidence since 1988, with eradication on the horizon, and a 78% decline in measles-associated mortality from 2000 to 2008 With the introduction of Haemophilus influenzae type b (Hib) vaccine, HepB vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine into many countries' routine vaccination schedules, further reductions in morbidity and mortality are expected. However, based on an annual global birth cohort of approximately 130 million, an estimated 23 million infants worldwide still do not receive the benefits of routine vaccination (i.e., 3 doses of DTP during the first year of life). The Global Immunization Vision and Strategy (GIVS), developed in 2005 by WHO and UNICEF, assists countries in strengthening immunization programs and vaccinating more persons. GIVS aims to achieve 90% national 3-dose DTP (DTP3) coverage by age 12 months in all countries, and 80% coverage in every district or equivalent administrative unit by 2010 (and to sustain these levels through 2015). This report summarizes global routine vaccination coverage during 2000--2009 and progress toward achieving GIVS goals. PMID:21030941

  12. Oral vaccination and protection of striped skunks (Mephitis mephitis) against rabies using ONRAB®.

    PubMed

    Brown, L J; Rosatte, R C; Fehlner-Gardiner, C; Ellison, J A; Jackson, F R; Bachmann, P; Taylor, J S; Franka, R; Donovan, D

    2014-06-17

    Skunks are one of the most important rabies vector species in North America due to their wide geographic distribution, high susceptibility to the rabies virus, and tendency to inhabit areas around human dwellings and domestic animals. Oral vaccination is a cost-effective, socially acceptable technique often used to control rabies in terrestrial wildlife; however, control of rabies in skunks has proven especially challenging due to the lack of a vaccine effective by the oral route in this species. In this study, we examined the antibody response of captive striped skunks (Mephitis mephitis) to ONRAB(®) and tested the protection afforded by the vaccine against rabies virus. Thirty-one skunks were each offered one ONRAB(®) vaccine bait, 25 skunks were administered ONRAB(®) via direct instillation into the oral cavity (DIOC) and ten controls received no vaccine. A blood sample was collected from controls and vaccinates 6 weeks prior to treatment, and then 5 and 7 weeks post-vaccination (PV). A competitive ELISA was used to detect rabies antibody (RAb). Pre-vaccination sera for all skunks, and sera for all controls throughout the serology study, were negative for RAb. Fifty-eight percent (18/31) of skunks in the bait group and 100% (25/25) of skunks that received ONRAB(®) DIOC had detectable RAb by 7 week PV. All 10 controls succumbed to experimental rabies infection. In the group of skunks administered ONRAB(®) DIOC, 100% (23/23) survived challenge 247 days PV. Survival of skunks presented ONRAB(®) baits was 81% (25/31). In the bait group, all 18 skunks that had detectable RAb by 7 week PV survived challenge. Seven additional skunks without detectable RAb prior to week 7 PV also survived. Lack of any remarkable pathology in study animals, together with positive serology and challenge results, supports that ONRAB(®) is a safe and effective oral rabies vaccine for use in skunks. PMID:24814554

  13. Duration of the immune response to MMR vaccine in children of two age-different groups.

    PubMed

    Li Volti, S; Giammanco-Bilancia, G; Grassi, M; Garozzo, R; Gluck, R; Giammanco, G

    1993-05-01

    A combined vaccine against measles, mumps and rubella (MMR) was administered to both a group of children aged 10-12 months simultaneously with booster doses of compulsory diphtheria-tetanus toxoids and oral poliovirus vaccine and a group of children aged 15-24 months who had previously received booster doses of the compulsory vaccines. Apart from one subject belonging to the second group who was non responder and one from the same group who did not seroconvert against the mumps virus alone, 5 to 6 weeks after MMR vaccine administration we found protective levels of antibodies against measles, mumps and rubella viruses in all children. The follow up of both groups at 3 years did not reveal difference between the two groups. Protective levels of serum antibodies against measles and mumps were found in the two groups, although a significant decline of rubella antibodies was shown (p < 0.05). Since the immunogenicity of the vaccines in the two groups did not differ, we recommend that the scientific community reconsider the vaccination schedule until now recommended. In our opinion the MMR vaccine should be administered simultaneously with booster doses of diphtheria-tetanus toxoids and oral poliovirus vaccine at 10-12 months of age because this policy improves parents' compliance, markedly reduces community costs and simplifies routine immunization schedule. PMID:8405317

  14. Deaths following vaccination: What does the evidence show?

    PubMed Central

    Miller, Elaine R.; Moro, Pedro L.; Cano, Maria; Shimabukuro, Tom

    2015-01-01

    Vaccines are rigorously tested and monitored and are among the safest medical products we use. Millions of vaccinations are given to children and adults in the United States each year. Serious adverse reactions are rare. However, because of the high volume of use, coincidental adverse events including deaths, that are temporally associated with vaccination, do occur. When death occurs shortly following vaccination, loved ones and others might naturally question whether it was related to vaccination. A large body of evidence supports the safety of vaccines, and multiple studies and scientific reviews have found no association between vaccination and deaths except in rare cases. During the US multi-state measles outbreak of 2014–2015, unsubstantiated claims of deaths caused by measles, mumps, and rubella (MMR) vaccine began circulating on the Internet, prompting responses by public health officials to address common misinterpretations and misuses of vaccine safety surveillance data, particularly around spontaneous reports submitted to the US Vaccine Adverse Event Reporting System (VAERS). We summarize epidemiologic data on deaths following vaccination, including examples where reasonable scientific evidence exists to support that vaccination caused or contributed to deaths. Rare cases where a known or plausible theoretical risk of death following vaccination exists include anaphylaxis, vaccine-strain systemic infection after administration of live vaccines to severely immunocompromised persons, intussusception after rotavirus vaccine, Guillain-Barré syndrome after inactivated influenza vaccine, fall-related injuries associated with syncope after vaccination, yellow fever vaccine-associated viscerotropic disease or associated neurologic disease, serious complications from smallpox vaccine including eczema vaccinatum, progressive vaccinia, postvaccinal encephalitis, myocarditis, and dilated cardiomyopathy, and vaccine-associated paralytic poliomyelitis from oral

  15. Deaths following vaccination: What does the evidence show?

    PubMed

    Miller, Elaine R; Moro, Pedro L; Cano, Maria; Shimabukuro, Tom T

    2015-06-26

    Vaccines are rigorously tested and monitored and are among the safest medical products we use. Millions of vaccinations are given to children and adults in the United States each year. Serious adverse reactions are rare. However, because of the high volume of use, coincidental adverse events including deaths, that are temporally associated with vaccination, do occur. When death occurs shortly following vaccination, loved ones and others might naturally question whether it was related to vaccination. A large body of evidence supports the safety of vaccines, and multiple studies and scientific reviews have found no association between vaccination and deaths except in rare cases. During the US multi-state measles outbreak of 2014-2015, unsubstantiated claims of deaths caused by measles, mumps, and rubella (MMR) vaccine began circulating on the Internet, prompting responses by public health officials to address common misinterpretations and misuses of vaccine safety surveillance data, particularly around spontaneous reports submitted to the US Vaccine Adverse Event Reporting System (VAERS). We summarize epidemiologic data on deaths following vaccination, including examples where reasonable scientific evidence exists to support that vaccination caused or contributed to deaths. Rare cases where a known or plausible theoretical risk of death following vaccination exists include anaphylaxis, vaccine-strain systemic infection after administration of live vaccines to severely immunocompromised persons, intussusception after rotavirus vaccine, Guillain-Barré syndrome after inactivated influenza vaccine, fall-related injuries associated with syncope after vaccination, yellow fever vaccine-associated viscerotropic disease or associated neurologic disease, serious complications from smallpox vaccine including eczema vaccinatum, progressive vaccinia, postvaccinal encephalitis, myocarditis, and dilated cardiomyopathy, and vaccine-associated paralytic poliomyelitis from oral

  16. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine.

    PubMed

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-04-01

    Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways. PMID:23453730

  17. Molecular Properties of Poliovirus Isolates: Nucleotide Sequence Analysis, Typing by PCR and Real-Time RT-PCR.

    PubMed

    Burns, Cara C; Kilpatrick, David R; Iber, Jane C; Chen, Qi; Kew, Olen M

    2016-01-01

    Virologic surveillance is essential to the success of the World Health Organization initiative to eradicate poliomyelitis. Molecular methods have been used to detect polioviruses in tissue culture isolates derived from stool samples obtained through surveillance for acute flaccid paralysis. This chapter describes the use of realtime PCR assays to identify and serotype polioviruses. In particular, a degenerate, inosine-containing, panpoliovirus (panPV) PCR primer set is used to distinguish polioviruses from NPEVs. The high degree of nucleotide sequence diversity among polioviruses presents a challenge to the systematic design of nucleic acid-based reagents. To accommodate the wide variability and rapid evolution of poliovirus genomes, degenerate codon positions on the template were matched to mixed-base or deoxyinosine residues on both the primers and the TaqMan™ probes. Additional assays distinguish between Sabin vaccine strains and non-Sabin strains. This chapter also describes the use of generic poliovirus specific primers, along with degenerate and inosine-containing primers, for routine VP1 sequencing of poliovirus isolates. These primers, along with nondegenerate serotype-specific Sabin primers, can also be used to sequence individual polioviruses in mixtures. PMID:26983735

  18. Phylogenetic Analysis of Poliovirus Sequences.

    PubMed

    Jorba, Jaume

    2016-01-01

    Comparative genomic sequencing is a major surveillance tool in the Polio Laboratory Network. Due to the rapid evolution of polioviruses (~1 % per year), pathways of virus transmission can be reconstructed from the pathways of genomic evolution. Here, we describe three main phylogenetic methods; estimation of genetic distances, reconstruction of a maximum-likelihood (ML) tree, and estimation of substitution rates using Bayesian Markov chain Monte Carlo (MCMC). The data set used consists of complete capsid sequences from a survey of poliovirus sequences available in GenBank. PMID:26983737

  19. Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine

    PubMed Central

    Sirskyj, Danylo; Kumar, Ashok; Azizi, Ali

    2016-01-01

    Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future. PMID:27384558

  20. Use of rhodamine B as a biomarker for oral plague vaccination of prairie dogs.

    PubMed

    Fernandez, Julia Rodriguez-Ramos; Rocke, Tonie E

    2011-07-01

    Oral vaccination against Yersinia pestis could provide a feasible approach for controlling plague in prairie dogs (Cynomys spp.) for conservation and public health purposes. Biomarkers are useful in wildlife vaccination programs to demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential biomarker for oral plague vaccination because it allows nonlethal sampling of animals through hair, blood, and feces. We found that RB is an appropriate marker for bait uptake studies of <60 days in black-tailed prairie dogs (C. ludovicianus) when used at concentrations <0.5% of bait mass dosed to deliver >10 mg RB per kg target animal mass. Whiskers with follicles provided the best sample for RB detection. PMID:21719849

  1. Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine.

    PubMed

    Sirskyj, Danylo; Kumar, Ashok; Azizi, Ali

    2016-01-01

    Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future. PMID:27384558

  2. An oral Aujeszky's disease vaccine (YS-400) induces neutralizing antibody in pigs

    PubMed Central

    2016-01-01

    Purpose Aujeszky's disease (AD) is an economically important disease affecting both wild and domestic pigs of the species Sus scrofa. A previous study yielded serological evidence of AD in Korean wild boars, which could spread AD to other animals. A new Aujeszky's disease virus (ADV) bait vaccine is required to prevent AD outbreaks in swine. In the present study, we investigated the safety and immunogenicity of a gE-deleted marker vaccine, strain YS-400, in young domestic pigs. Materials and Methods The YS-400 strain was propagated in Vero cells, and the trial ADV bait vaccine (a vaccine blister in a matrix including an attractant) was prepared. Pigs were orally immunized with the vaccine (2 mL, 107.5 TCID50/mL) delivered using a syringe or in the bait vaccine. The animals were observed for 9 weeks after vaccination, and immunogenicity was assessed using a virus neutralization (VN) test and enzyme linked immunosorbent assay. Results The YS-400 strain was non-pathogenic to pigs when given orally and induced high VN titers (1:32-1:128) 6 weeks post-administration. Of the pigs given the ADV bait vaccine twice or three times, 40% were seropositive by 2 weeks, and 100% were seropositive by 7 weeks after the first dose. Pigs that consumed the AD bait vaccine three times developed VN titers that were slightly higher than those of pigs given the vaccine twice. Conclusion Domestic pigs given the trial ADV bait vaccine exhibited no adverse effects and developed high VN titers against ADV, indicating that the YS-400 strain is safe and can prevent ADV infection in domestic pigs. PMID:27489803

  3. Alga-produced cholera toxin-Pfs25 fusion proteins as oral vaccines.

    PubMed

    Gregory, James A; Topol, Aaron B; Doerner, David Z; Mayfield, Stephen

    2013-07-01

    Infectious diseases disproportionately affect indigent regions and are the greatest cause of childhood mortality in developing countries. Practical, low-cost vaccines for use in these countries are paramount to reducing disease burdens and concomitant poverty. Algae are a promising low-cost system for producing vaccines that can be orally delivered, thereby avoiding expensive purification and injectable delivery. We engineered the chloroplast of the eukaryotic alga Chlamydomonas reinhardtii to produce a chimeric protein consisting of the 25-kDa Plasmodium falciparum surface protein (Pfs25) fused to the β subunit of the cholera toxin (CtxB) to investigate an alga-based whole-cell oral vaccine. Pfs25 is a promising malaria transmission-blocking vaccine candidate that has been difficult to produce in traditional recombinant systems due to its structurally complex tandem repeats of epidermal growth factor-like domains. The noncatalytic CtxB domain of the cholera holotoxin assembles into a pentameric structure and acts as a mucosal adjuvant by binding GM1 ganglioside receptors on gut epithelial cells. We demonstrate that CtxB-Pfs25 accumulates as a soluble, properly folded and functional protein within algal chloroplasts, and it is stable in freeze-dried alga cells at ambient temperatures. In mice, oral vaccination using freeze-dried algae that produce CtxB-Pfs25 elicited CtxB-specific serum IgG antibodies and both CtxB- and Pfs25-specific secretory IgA antibodies. These data suggest that algae are a promising system for production and oral delivery of vaccine antigens, but as an orally delivered adjuvant, CtxB is best suited for eliciting secretory IgA antibodies for vaccine antigens against pathogens that invade mucosal surfaces using this strategy. PMID:23603678

  4. Human Enterovirus 71 Protein Displayed on the Surface of Saccharomyces cerevisiae as an Oral Vaccine.

    PubMed

    Zhang, Congdang; Wang, Yi; Ma, Shuzhi; Li, Leike; Chen, Liyun; Yan, Huimin; Peng, Tao

    2016-06-01

    Human enterovirus 71 (EV-A71), a major agent of hand, foot, and mouth disease, has become an important public health issue in recent years. No effective antiviral or vaccines against EV-A71 infection are currently available. EV-A71 infection intrudes bodies through the gastric mucosal surface and it is necessary to enhance mucosal immune response to protect children from these pathogens. Recently, the majority of EV-A71 vaccine candidates have been developed for parenteral immunization. However, parenteral vaccine candidates often induce poor mucosal responses. On the other hand, oral vaccines could induce effective mucosal and systemic immunity, and could be easily and safely administered. Thus, proper oral vaccines have attached more interest compared with parenteral vaccine. In this study, the major immunogenic capsid protein of EV-A71 was displayed on the surface of Saccharomyces cerevisiae. Oral immunization of mice with surface-displayed VP1 S. cerevisiae induced systemic humoral and mucosal immune responses, including virus-neutralizing titers, VP1-specific antibody, and the induction of Th1 immune responses in the spleen. Furthermore, oral immunization of mother mice with surface-displayed VP1 S. cerevisiae conferred protection to neonatal mice against the lethal EV-A71 infection. Furthermore, we observed that multiple boost immunization as well as higher immunization dosage could induce higher EV-A71-specific immune response. Our results demonstrated that surface-displayed VP1 S. cerevisiae could be used as potential oral vaccine against EV-A71 infection. PMID:27259043

  5. Plant-made oral vaccines against human infectious diseases-Are we there yet?

    PubMed

    Chan, Hui-Ting; Daniell, Henry

    2015-10-01

    Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches. PMID:26387509

  6. Plant-made oral vaccines against human infectious diseases—Are we there yet?

    PubMed Central

    Chan, Hui-Ting; Daniell, Henry

    2016-01-01

    Summary Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches. PMID:26387509

  7. Potential for use of retinoic acid as an oral vaccine adjuvant

    PubMed Central

    Mwanza-Lisulo, Mpala; Kelly, Paul

    2015-01-01

    Despite the heavy burden of diarrhoeal disease across much of the tropical world, only two diarrhoea-causing pathogens, cholera and rotavirus, are the target of commercially available vaccines. Oral vaccines are generally less immunogenic than the best parenteral vaccines, but the reasons for this are still debated. Over the past decade, several lines of evidence from work in experimental animals have suggested that all-trans retinoic acid (ATRA), a form of vitamin A which is highly transcriptionally active, can alter the homing receptor expression of T lymphocytes. Increased expression of α4β7 integrin and the chemokine receptor CCR9 following exposure to ATRA can be used to redirect T cells to the gut. Early work in human volunteers suggests that oral ATRA administration 1 h prior to dosing with oral typhoid vaccine can augment secretion of specific IgA against vaccine-derived lipopolysaccharide into gut secretions. In this review, we set out the rationale for using ATRA in this way and assess its likely applicability to vaccination programmes for protection of children in low-income countries from the considerable mortality caused by diarrhoeal disease. Comparison of recent work in experimental animals, non-human primates and men suggests that a more detailed understanding of ATRA dosage and kinetics will be important to taking forward translational work into human vaccinology. PMID:25964457

  8. Oral vaccination against raccoon rabies: landscape heterogeneity and timing of distribution influence wildlife contact rates with the ONRAB vaccine bait.

    PubMed

    Boyer, Jean-Philippe; Canac-Marquis, Pierre; Guérin, Daniel; Mainguy, Julien; Pelletier, Fanie

    2011-07-01

    Aerial distribution of oral vaccine baits is one of the available strategies for controlling the spread of infectious wildlife diseases. This technique has commonly been used to control rabies in wild carnivores and, together with other techniques, was used to immunize wild populations of raccoons (Procyon lotor) and striped skunks (Mephitis mephitis) after the detection of the first rabid raccoon in the province of Quebec, Canada, in 2006. Vaccine bait distribution was conducted over large areas where agricultural land is dominant but interspersed with residual forest patches. Our objective was to evaluate the effect of habitat (forest vs. agricultural crops) in space and time on the contact rate between wildlife and the ONRAB(®) vaccine bait, a recent alternative to the V-RG(®). Four transects of eight vaccine baits each were installed parallel to, and at different distances from, the forest's edge (under forest cover, at field-forest edge, and at 50 and 200 m from forest edge in agricultural crops) at three sites composed of various crop types interspersed with forest patches. This experiment was conducted during three periods (late spring, 1-7 June; summer, 27 July-2 August; and fall, 24-30 October) in 2009. Contact rates with vaccine baits were monitored for 7 days in each period to evaluate the potential temporal variations generated within the habitat types. Contact rates with ONRAB vaccine baits were highest under forest cover and in the fall. Of 13 species observed in proximity to the vaccine baits, raccoons were the most frequent (49.5%, n=55 visits). Our study underlines the importance of taking into account landscape heterogeneity and timing of distribution when planning the distribution of vaccine baits to control rabies in raccoons. PMID:21719823

  9. Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

    PubMed

    Herzog, Christian

    2016-01-01

    Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. PMID:27425792

  10. The relation between acute persisting spinal paralysis and poliomyelitis vaccine (oral): results of a WHO enquiry*

    PubMed Central

    1976-01-01

    The present report presents the findings in 8 countries at the end of the first 5 years of an international investigation into the possible relationship between acute persisting spinal paralysis and the use of oral poliomyelitis vaccine. The most striking finding was the high association with type 3 virus in the recipient cases and with type 2 virus in the “contacts” and “possible contacts”. Most of the cases in the recipient groups occurred in children under 5 years of age in all countries, but in the “contact” groups in the countries in which vaccination is offered through the year, many of the cases occurred in the non-immune parents of recently vaccinated infants. There were marked differences among countries, and it was not possible to pinpoint a single factor as the sole cause. However, the quality of the vaccine clearly played an important role. For some time, and certainly at the beginning of this enquiry, some of the countries were using vaccine from the same source without continuous external control and were using seed viruses at high passage levels. The situation changed during the enquiry and the incidence of paralytic cases decreased. The enquiry will be continued and particular efforts will be made to establish the cause of the associated paralysis. The findings of the enquiry confirm that oral Sabin poliomyelitis vaccines are among the safest vaccines in use today. PMID:1086727

  11. Development of two salmonella-based oral vaccines against human respiratory syncytial virus.

    PubMed

    Azizi Jalilian, F; Yusoff, K; Suhaimi, S; Amini, R; Sekawi, Z; Jahanshiri, F

    2015-01-01

    Human respiratory syncytial virus is the most common cause of bronchiolitis and other respiratory infections in infants and the elderly worldwide. We have developed two new oral vaccines using Salmonella typhi TY21a to carry and express the immunogenic epitopes of RSV fusion (F) and attachment (G) glycoproteins on its surface, separately. To evaluate the efficacy of the designed vaccines, BALB/c mice were orally immunized and then infected with RSV. Immune response analyses showed that cellmediated, mucosal and humoral immunity in the vaccinated mice were significantly enhanced compared to the control group. Both vaccines generated a balanced Th1/Th2 immune response which is crucial for efficiency of vaccines against RSV. Furthermore, histopathological examination proved that these vaccines were safe as they did not cause any Th2-associated adverse effects in the lungs of RSV-infected mice. The findings of this research suggest that Salmonella-F and Salmonella-G vaccine candidates may have strong potential to prevent RSV infection. PMID:25864737

  12. The golden jubilee of vaccination against poliomyelitis.

    PubMed

    John, T Jacob

    2004-01-01

    Inactivated poliovirus vaccine (IPV), developed in the USA by Jonas Salk in the early 1950s, was field tested in 1954, and found to be safe and effective. The year 2004 marks the golden jubilee of this breakthrough. From 1955 IPV was used extensively in the US and polio incidence declined by more than 95 per cent. However, in 1962, when oral poliovirus vaccine (OPV) became available, the national policy was shifted to its exclusive use, for reasons other than science and economics. The World Health Organisation (WHO) also adopted the policy of the exclusive use of OPV in developing countries. Thus IPV fell into disrepute in much of the world, while Northern European countries continued to use it. New research led to improving its potency, reducing its manufacturing costs and combining it with the diphtheria-tetanus-pertussis (DTP) vaccine to simplify its administration and reduce programmatic costs. All countries that chose to persist with IPV eliminated poliovirus circulation without OPV-induced polio or the risk of live vaccine viruses reverting to wild-like nature. IPV is highly immunogenic, confers mucosal immunity and exerts herd protective effect, all qualities of a good vaccine. It can be used in harmony with the extendend programme on immunization (EPI) schedule of infant immunisation with DTP, thus reducing programmatic costs. During the last ten years IPV has once again regained its popularity and some 25 industrialised countries use it exclusively. The demand is increasing from other countries and the supply has not caught up, leaving market forces to dictate the sale price of IPV. Anticipating such a turn of events India had launched its own IPV manufacturing programme in 1987, but the project was closed in 1992. Today it is not clear if we can complete the job of global polio eradication without IPV, on account of the genetic instability of OPV and the consequent tendency of vaccine viruses to revert to wild-like properties. The option to use IPV is

  13. Strategies for Developing Oral Vaccines for Human Papillomavirus (HPV) Induced Cancer using Nanoparticle mediated Delivery System.

    PubMed

    Uddin, Mohammad Nasir; Kouzi, Samir A; Hussain, Muhammad Delwar

    2015-01-01

    Human Papillomaviruses (HPV) are a diverse group of small non-enveloped DNA viruses. Some HPVs are classified as low-risk as they are very rarely associated with neoplasia or cancer in the general population, and cause lenient warts. Other HPVs are considered as high-risk types because they are responsible for several important human cancers, including cervical cancer, a large proportion of other anogenital cancers, and a growing number of head and neck cancers. Transmission of HPV occurs primarily by skin-to-skin contact. The risk of contracting genital HPV infection and cervical cancer is influenced by sexual activity. Currently two prophylactic HPV vaccines, Gardasil® (Merck, USA) and Cervarix® (GlaxoSmithKline, UK), are available and recommended for mass immunization of adolescents. However, these vaccines have limitations as they are expensive and require cold chain storage and trained personnel to administer them by injection. The use of nano or micro particulate vaccines could address most of these limitations as they are stable at room temperature, inexpensive to produce and distribute to resource poor regions, and can be administered orally without the need for adjuvants in the formulation. Also it is possible to increase the efficiency of these particulate vaccines by decorating the surface of the nano or micro particulates with suitable ligands for targeted delivery. Oral vaccines, which can be delivered using particulate formulations, have the added potential to stimulate mucosa-associated lymphoid tissue located in the digestive tract and the gut-associated lymphoid tissue, both of which are important for the induction of effective mucosal response against many viruses. In addition, oral vaccines provide the opportunity to reduce production and administration costs and are very patient compliant. This review elaborately discusses different strategies that can be pursued to develop a nano or micro particulate oral vaccine for HPV induced cancers and

  14. A developing country perspective on vaccine-associated paralytic poliomyelitis.

    PubMed Central

    John, T. Jacob

    2004-01-01

    When the Expanded Programme on Immunization was established and oral poliovirus vaccine (OPV) was introduced for developing countries to use exclusively, national leaders of public health had no opportunity to make an informed choice between OPV and the inactivated poliovirus vaccine (IPV). Today, as progress is made towards the goal of global eradication of poliomyelitis attributable to wild polioviruses, all developing countries where OPV is used face the risk of vaccine-associated paralytic poliomyelitis (VAPP). Until recently, awareness of VAPP has been poor and quantitative risk analysis scanty but it is now well known that the continued use of OPV perpetuates the risk of VAPP. Discontinuation or declining immunization coverage of OPV will increase the risk of emergence of circulating vaccine-derived polioviruses (cVDPV) that re-acquire wild virus-like properties and may cause outbreaks of polio. To eliminate the risk of cVDPV, either very high immunization coverage must be maintained as long as OPV is in use, or IPV should replace OPV. Stopping OPV without first achieving high immunization coverage with IPV is unwise on account of the possibility of emergence of cVDPV. Increasing numbers of developed nations prefer IPV, and manufacturing capacities have not been scaled up, so its price remains prohibitively high and unaffordable by developing countries, where, in addition, large-scale field experience with IPV is lacking. Under these circumstances, a policy shift to increase the use of IPV in national immunization programmes in developing countries is a necessary first step; once IPV coverage reaches high levels (over 85%), the withdrawal of OPV may begin. PMID:15106301

  15. Feasibility and efficacy of oral rabies vaccine SAG2 in endangered Ethiopian wolves.

    PubMed

    Sillero-Zubiri, Claudio; Marino, Jorgelina; Gordon, Christopher H; Bedin, Eric; Hussein, Alo; Regassa, Fekede; Banyard, Ashley; Fooks, Anthony R

    2016-09-14

    Diseases are a major cause of population declines in endangered populations of several canid species. Parenteral vaccination efforts to protect Ethiopian wolves (Canis simensis) from rabies have targeted the domestic dog reservoir, or the wolves themselves in response to confirmed outbreaks. Oral vaccination offers a more cost-efficient, safe and proactive approach to protect Ethiopian wolves and other threatened canids from rabies. Field trials of the oral vaccine Rabigen® SAG2Dog were undertaken in the Bale Mountains of southeastern Ethiopia. Four different bait types and three delivery methods were tested in twelve Ethiopian wolf packs, and the oral vaccine (using the preferred bait) was trialled in three packs. Vaccine uptake and immunization rates were measured through direct observations and in live-trapped animals through the assessment of biomarker levels and serological status. Commercial baits were never taken by wolves; goat meat baits had the highest uptake, compared to rodent and intestine baits. Targeted delivery from horseback and nocturnal delivery within a pack's territory performed favourably compared to random bait distribution. Bait uptake by non-target species was lowest during the nocturnal blind distribution. Of 21 wolves trapped after vaccination, 14 were positive for the biomarker iophenoxic acid (i.e. ingested the bait and most likely pierced the sachet with the vaccine). Of these, 86% (n=12/14) had levels considered sufficient to provide protective immunity to wildlife (⩾0.20IU/ml), and 50% (n=7/14) demonstrated antibody titres above the universally recognised threshold (⩾0.5IU/ml) -the baseline average was 0.09IU/ml (n=12 wolves). All but one of the wolves vaccinated in 2014 were alive 14months later. Our trials confirm the potential for SAG2, delivered in a goat meat bait, to effectively protect Ethiopian wolves against rabies, supporting the initiative for a more efficient and proactive approach to manage and eventually eliminate

  16. Protection of gruntlings against classical swine fever virus-infection after oral vaccination of sows with C-strain vaccine.

    PubMed

    Kaden, V; Lange, E; Müller, T; Teuffert, J; Teifke, J P; Riebe, R

    2006-12-01

    The objective of this study was to investigate the maternal protection of gruntlings derived from wild sows vaccinated orally against classical swine fever (CSF) using C-strain vaccine. Three vaccinated sows and one unvaccinated control sow were included. Challenge infection of the progeny was carried out either intranasally or by contact at the beginning of the third month of life (61-65 days post-natum). Whereas, two of three litters had maternal antibodies, the progeny of one vaccinated sow was seronegative at challenge. The progeny of the control sow, which was challenged by contact infection, developed moderate clinical signs except for one animal which became ill and died. Two gruntlings derived from the vaccinated sows also died of CSF, although one of them had a relatively high maternal antibody titre (128 ND(50)). The transient infection and partial virus shedding observed in a small number of gruntlings with maternal antibodies and the fact that one animal with maternal antibodies became ill and died confirm the incomplete maternal protection at this age. The reason for this incomplete protection is discussed. As none of the surviving gruntlings could be shown to carry CSFV or viral RNA at the end of the experiment (36 or 70 d.p.i.), it may be concluded that these animals do not represent a potential CSFV reservoir. PMID:17123422

  17. Room temperature stabilization of oral, live attenuated Salmonella enterica serovar Typhi-vectored vaccines.

    PubMed

    Ohtake, Satoshi; Martin, Russell; Saxena, Atul; Pham, Binh; Chiueh, Gary; Osorio, Manuel; Kopecko, Dennis; Xu, Deqi; Lechuga-Ballesteros, David; Truong-Le, Vu

    2011-03-24

    Foam drying, a modified freeze drying process, was utilized to produce a heat-stable, live attenuated Salmonella Typhi 'Ty21a' bacterial vaccine. Ty21a vaccine was formulated with pharmaceutically approved stabilizers, including sugars, plasticizers, amino acids, and proteins. Growth media and harvesting conditions of the bacteria were also studied to enhance resistance to desiccation stress encountered during processing as well as subsequent storage at elevated temperatures. The optimized Ty21a vaccine, formulated with trehalose, methionine, and gelatin, demonstrated stability for approximately 12 weeks at 37°C (i.e., time required for the vaccine to decrease in potency by 1log(10)CFU) and no loss in titer at 4 and 25°C following storage for the same duration. Furthermore, the foam dried Ty21a elicited a similar immunogenic response in mice as well as protection in challenge studies compared to Vivotif™, the commercial Ty21a vaccine. The enhanced heat stability of the Ty21a oral vaccine, or Ty21a derivatives expressing foreign antigens (e.g. anthrax), could mitigate risks of vaccine potency loss during long-term storage, shipping, delivery to geographical areas with warmer climates or during emergency distribution following a bioterrorist attack. Because the foam drying process is conducted using conventional freeze dryers and can be readily implemented at any freeze drying manufacturing facility, this technology appears ready and appropriate for large scale processing of foam dried vaccines. PMID:21300096

  18. Room Temperature Stabilization of Oral, Live Attenuated Salmonella enterica serovar Typhi-Vectored Vaccines

    PubMed Central

    Ohtake, Satoshi; Martin, Russell; Saxena, Atul; Pham, Binh; Chiueh, Gary; Osorio, Manuel; Kopecko, Dennis; Xu, DeQi; Lechuga-Ballesteros, David; Truong-Le, Vu

    2011-01-01

    Foam drying, a modified freeze drying process, was utilized to produce a heat-stable, live attenuated Salmonella Typhi ‘Ty21a’ bacterial vaccine. Ty21a vaccine was formulated with pharmaceutically approved stabilizers, including sugars, plasticizers, amino acids, and proteins. Growth media and harvesting conditions of the bacteria were also studied to enhance resistance to desiccation stress encountered during processing as well as subsequent storage at elevated temperatures. The optimized Ty21a vaccine, formulated with trehalose, methionine, and gelatin, demonstrated stability for approximately 12 weeks at 37°C (i.e., time required for the vaccine to decrease in potency by 1log10 CFU) and no loss in titer at 4 and 25°C following storage for the same duration. Furthermore, the foam dried Ty21a elicited a similar immunogenic response in mice as well as protection in challenge studies compared to Vivotif™, the commercial Ty21a vaccine. The enhanced heat stability of the Ty21a oral vaccine, or Ty21a derivatives expressing foreign antigens (e.g. anthrax), could mitigate risks of vaccine potency loss during long term storage, shipping, delivery to geographical areas with warmer climates or during emergency distribution following a bioterrorist attack. Because the foam drying process is conducted using conventional freeze dryers and can be readily implemented at any freeze drying manufacturing facility, this technology appears ready and appropriate for large scale processing of foam dried vaccines. PMID:21300096

  19. Oral vaccination of first-feeding Atlantic salmon, Salmo salar L., confers greater protection against yersiniosis than immersion vaccination.

    PubMed

    Ghosh, Bikramjit; Nguyen, Thu D; Crosbie, Philip B B; Nowak, Barbara F; Bridle, Andrew R

    2016-01-27

    Yersinia ruckeri is a ubiquitous pathogen of finfish capable of causing major mortalities in farmed fish stocks. It can be transmitted vertically from parent to progeny as well as horizontally in the water column from both clinically infected fish and asymptomatic carriers, and is consequently capable of infecting fish at early stages of development. Immunisation strategies that can protect small fry are therefore critical for the effective management of fish health, as is the ability to detect covertly infected fish. In this study, first-feeding Atlantic salmon fry (<0.5 g) were immunised either by oral administration of a microencapsulated Y. ruckeri vaccine formulation (0.38 g initial weight), or via immersion in bacterin suspension (0.26 g), with and without a booster immersion vaccination at 1g size. Protection in groups receiving only immersion immunisation did not differ significantly from untreated controls when challenged with Y. ruckeri at approximately 5 g size, while orally immunised fish were significantly better protected than untreated controls (F=4.38, df=4,10, P=0.026), with RPS varying between 29.4% (ORAL) and 51% (ORAL+DIP). A quantitative real-time PCR assay was used to successfully detect covertly infected fish among challenge survivors, indicating more than 50% of surviving fish in each group were infected with no significant differences between immunised fish and untreated controls. PMID:26724544

  20. Safety evaluation of adenovirus type 4 and type 7 vaccine live, oral in military recruits.

    PubMed

    Choudhry, Azhar; Mathena, Julie; Albano, Jessica D; Yacovone, Margaret; Collins, Limone

    2016-08-31

    Before the widespread adoption of vaccination, adenovirus type 4 and type 7 were long associated with respiratory illnesses among military recruits. When supplies were depleted and vaccination was suspended in 1999 for approximately a decade, respiratory illnesses due to adenovirus infections resurged. In March 2011, a new live, oral adenovirus vaccine was licensed by the US Food and Drug Administration and was first universally administered to military recruits in October 2011, leading to rapid, dramatic elimination of the disease within a few months. As part of licensure, a postmarketing study (Sentinel Surveillance Plan) was performed to detect potential safety signals within 42days after immunization of military recruits. This study retrospectively evaluated possible adverse events related to vaccination using data from the Armed Forces Health Surveillance Branch Defense Medical Surveillance System (DMSS) database. Among 100,000 recruits who received the adenovirus vaccine, no statistically significant greater risk of prespecified medical events was observed within 42days after vaccination when compared with a historical cohort of 100,000 unvaccinated recruits. In an initial statistical analysis of International Classification of Disease, 9th Revision, Clinical Modification codes, a statistically significant higher risk for 19 other (not prespecified) medical events occurring in 5 or more recruits was observed among vaccinated compared with unvaccinated groups. After case record data abstraction for attribution and validation, two events (psoriasis [21 vs 7 cases] and serum reactions [12 vs 4 cases]) occurred more frequently in the vaccinated cohort. A causal relation of these rare events with adenovirus vaccination could not be established given confounding factors in the DMSS, such as coadministration of other vaccines and incomplete or inaccurate medical information, for some recruits. Prospective surveillance assessing these uncommon, but potentially

  1. 78 FR 49444 - Oral Rabies Vaccine Trial; Availability of a Supplement to an Environmental Assessment and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-14

    ... in the Federal Register (77 FR 49409-49410, Docket No. APHIS-2012-0052) a notice \\1\\ announcing the... presented in an appendix to the EA. On June 5, 2013, we published in the Federal Register (78 FR 33798... relative to an oral rabies vaccination field trial in New Hampshire, New York, Ohio, Vermont, ] and...

  2. 77 FR 40322 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-09

    ... raccoon (eastern States), coyote (Texas), and gray fox (Texas, New Mexico, and Arizona) rabies virus variants to new areas. While this vaccine has proven to be orally effective in raccoons, coyotes, and foxes..., skunks, foxes, and coyotes. The proposed field trial would take place within approximately 10,483...

  3. 76 FR 56731 - Oral Rabies Vaccine Trial; Availability of an Environmental Assessment and Finding of No...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-14

    ...We are advising the public that an environmental assessment and finding of no significant impact have been prepared by the Animal and Plant Health Inspection Service relative to an oral rabies vaccination field trial in West Virginia. Based on its finding of no significant impact, the Animal and Plant Health Inspection Service has determined that an environmental impact statement need not be......

  4. Genome Sequence of Salmonella enterica Serovar Typhi Oral Vaccine Strain Ty21a.

    PubMed

    Xu, Deqi; Cisar, John O; Poly, Frédéric; Yang, Jinghua; Albanese, Jason; Dharmasena, Madushini; Wai, Tint; Guerry, Patricia; Kopecko, Dennis J

    2013-01-01

    Attenuated Salmonella enterica serovar Typhi strain Ty21a is an important vaccine for controlling typhoid fever and serves as an oral vector for delivering heterologous antigens. The key attenuating features of this randomly mutated strain remain in question. Genome sequencing has revealed 679 single nucleotide polymorphisms (SNPs), and will help define alterations contributing to Ty21a safety and immunogenicity. PMID:23969054

  5. Food-Grade Organisms as Vaccine Biofactories and Oral Delivery Vehicles.

    PubMed

    Rosales-Mendoza, Sergio; Angulo, Carlos; Meza, Beatriz

    2016-02-01

    The use of food-grade organisms as recombinant vaccine expression hosts and delivery vehicles has been explored during the past 25 years, opening new avenues for vaccinology. Considering that oral immunization is a beneficial approach in terms of costs, patient comfort, and protection of mucosal tissues, the use of food-grade organisms can lead to highly advantageous vaccines in terms of costs, easy administration, and safety. The organisms currently used for this purpose are bacteria (Lactobacillus and Bacillus), yeasts, algae, plants, and insect species. Herein, a comparative and updated scenario on the production of oral vaccines in food-grade organisms is provided and placed in perspective. The status of clinical evaluations and the adoption of this technology by the industry are highlighted. PMID:26708345

  6. Controlling of CSFV in European wild boar using oral vaccination: a review.

    PubMed

    Rossi, Sophie; Staubach, Christoph; Blome, Sandra; Guberti, Vittorio; Thulke, Hans-Hermann; Vos, Ad; Koenen, Frank; Le Potier, Marie-Frédérique

    2015-01-01

    Classical swine fever (CSF) is among the most detrimental diseases for the swine industry worldwide. Infected wild boar populations can play a crucial role in CSF epidemiology and controlling wild reservoirs is of utmost importance for preventing domestic outbreaks. Oral mass vaccination (OMV) has been implemented to control CSF in wild boars and limit the spill over to domestic pigs. This retrospective overview of vaccination experiences illustrates the potential for that option. The C-strain live vaccine was confirmed to be highly efficacious and palatable baits were developed for oral delivery in free ranging wild boars. The first field trials were performed in Germany in the 1990's and allowed deploying oral baits at a large scale. The delivery process was further improved during the 2000's among different European countries. Optimal deployment has to be early regarding disease emergence and correctly designed regarding the landscape structure and the natural food sources that can compete with oral baits. OMV deployment is also highly dependent on a local veterinary support working closely with hunters, wildlife and forestry agencies. Vaccination has been the most efficient strategy for CSF control in free ranging wild boar when vaccination is wide spread and lasting for a sufficient period of time. Alternative disease control strategies such as intensified hunting or creating physical boundaries such as fences have been, in contrast, seldom satisfactory and reliable. However, monitoring outbreaks has been challenging during and after vaccination deployment since OMV results in a low probability to detect virus-positive animals and the live-vaccine currently available does not allow serological differentiation of infected from vaccinated animals. The development of a new marker vaccine and companion test is thus a promising option for better monitoring outbreaks during OMV deployment as well as help to better determine when to stop vaccination efforts. After

  7. Controlling of CSFV in European wild boar using oral vaccination: a review

    PubMed Central

    Rossi, Sophie; Staubach, Christoph; Blome, Sandra; Guberti, Vittorio; Thulke, Hans-Hermann; Vos, Ad; Koenen, Frank; Le Potier, Marie-Frédérique

    2015-01-01

    Classical swine fever (CSF) is among the most detrimental diseases for the swine industry worldwide. Infected wild boar populations can play a crucial role in CSF epidemiology and controlling wild reservoirs is of utmost importance for preventing domestic outbreaks. Oral mass vaccination (OMV) has been implemented to control CSF in wild boars and limit the spill over to domestic pigs. This retrospective overview of vaccination experiences illustrates the potential for that option. The C-strain live vaccine was confirmed to be highly efficacious and palatable baits were developed for oral delivery in free ranging wild boars. The first field trials were performed in Germany in the 1990’s and allowed deploying oral baits at a large scale. The delivery process was further improved during the 2000’s among different European countries. Optimal deployment has to be early regarding disease emergence and correctly designed regarding the landscape structure and the natural food sources that can compete with oral baits. OMV deployment is also highly dependent on a local veterinary support working closely with hunters, wildlife and forestry agencies. Vaccination has been the most efficient strategy for CSF control in free ranging wild boar when vaccination is wide spread and lasting for a sufficient period of time. Alternative disease control strategies such as intensified hunting or creating physical boundaries such as fences have been, in contrast, seldom satisfactory and reliable. However, monitoring outbreaks has been challenging during and after vaccination deployment since OMV results in a low probability to detect virus-positive animals and the live-vaccine currently available does not allow serological differentiation of infected from vaccinated animals. The development of a new marker vaccine and companion test is thus a promising option for better monitoring outbreaks during OMV deployment as well as help to better determine when to stop vaccination efforts

  8. Cervical, Anal and Oral HPV in an Adolescent Inner-City Health Clinic Providing Free Vaccinations

    PubMed Central

    Schlecht, Nicolas F.; Burk, Robert D.; Nucci-Sack, Anne; Shankar, Viswanathan; Peake, Ken; Lorde-Rollins, Elizabeth; Porter, Richard; Linares, Lourdes Oriana; Rojas, Mary; Strickler, Howard D.; Diaz, Angela

    2012-01-01

    Objectives Published human papillomavirus (HPV) vaccine trials indicate efficacy is strongest for those naive to the vaccine-types. However, few high-risk young women have been followed and cervical HPV has been the predominant outcome measure. Methods We collected cervical and anal swabs, as well as oral rinse specimens from 645 sexually active inner-city young females attending a large adolescent health-clinic in New York City that offers free care and HPV vaccination. Specimens were tested for HPV-DNA using a MY09/MY11-PCR system. Type-specific prevalence of HPV at each anatomic site was compared for individuals by vaccination dose using generalized estimating equation logistic regression models. Results The majority of subjects reported being of non-Caucasian (92%) and/or Hispanic ethnicity (61%). Median age was 18 years (range:14–20). All had practiced vaginal sex, a third (33%) practiced anal sex, and most (77%) had also engaged in oral sex. At enrollment, 21% had not received the vaccine and 51% had received three doses. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types present in 7%, 6% and 1% of specimens, respectively. Comparing prevalence for vaccine types, the detection of HPV in the cervix of vaccinated compared to unvaccinated adolescents was significantly reduced: HPV6/11 (odds ratio [OR] = 0.19, 95%CI:0.06–0.75), HPV16 (OR = 0.31, 95%CI:0.11–0.88) and HPV18 (OR = 0.14, 95%CI:0.03–0.75). For anal HPV, the risk of detecting vaccine types HPV6/11 (OR = 0.27, 95%CI:0.10–0.72) and HPV18(OR = 0.12, 95%CI:0.01–1.16) were significantly reduced for vaccinated adolescents however, the risk for HPV16 was not significantly decreased (OR = 0.63, 95%CI:0.18–2.20). Conclusion HPV Prevalence is extremely high in inner-city female adolescents. Administration of the HPV vaccine reduced the risk for cervical HPV; however continued follow-up is required

  9. Protection of Monkeys Against Experimental Shigellosis with a Living Attenuated Oral Polyvalent Dysentery Vaccine

    PubMed Central

    Formal, Samuel B.; Kent, T. H.; May, H. C.; Palmer, A.; Falkow, S.; LaBrec, E. H.

    1966-01-01

    Formal, Samuel B. (Walter Reed Army Institute of Research, Washington, D.C.), T. H. Kent, H. C. May, A. Palmer, and E. H. LaBrec. Protection of monkeys against experimental challenge with a living attenuated oral polyvalent dysentery vaccine. J. Bacteriol. 91:17–22. 1966.—Virulent strains of Shigella flexneri 1b, S. flexneri 3, and S. sonnei I were mated with an Hfr strain of Escherichia coli K-12, and hybrids were selected for the xylose marker. One hybrid strain of each of the serotypes was chosen for study of their biological characteristics. Their capacity to cause a fatal enteric infection in starved guinea pigs was reduced, they failed to cause dysentery when fed to monkeys, they caused keratoconjunctivitis in the guinea pig eye, and they penetrated HeLa cells. Two doses of a polyvalent oral vaccine composed of S. flexneri 1b, 2a, and 3, and S. sonnei I hybrid strains were fed to groups of monkeys at an interval of 4 to 7 days, and they, together with controls, were challenged 10 days after the last dose with one or another of the virulent parent dysentery strains. A significant degree of protection was afforded in all vaccinated groups with the exception of one group challenged with S. flexneri 6, a component not included in the vaccine. When animals were challenged with virulent S. flexneri 2a 1 month after oral vaccination, they were also protected. The vaccine produced a rise in serum antibody, but we were not able to detect coproantibody in saline extracts of feces from animals which received the vaccine. PMID:4957431

  10. Next Generation Inactivated Polio Vaccine Manufacturing to Support Post Polio-Eradication Biosafety Goals

    PubMed Central

    Thomassen, Yvonne E.; van ’t Oever, Aart G.; van Oijen, Monique G. C. T.; Wijffels, René H.; van der Pol, Leo A.; Bakker, Wilfried A. M.

    2013-01-01

    Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV) is scheduled. Moreover, a manufacturing process, using attenuated virus strains instead of wild-type polioviruses, is demanded to enhance worldwide production of IPV, especially in low- and middle income countries. Therefore, development of an IPV from attenuated (Sabin) poliovirus strains (sIPV) was pursued. Starting from the current IPV production process based on wild type Salk strains, adaptations, such as lower virus cultivation temperature, were implemented. sIPV was produced at industrial scale followed by formulation of both plain and aluminium adjuvanted sIPV. The final products met the quality criteria, were immunogenic in rats, showed no toxicity in rabbits and could be released for testing in the clinic. Concluding, sIPV was developed to manufacturing scale. The technology can be transferred worldwide to support post polio-eradication biosafety goals. PMID:24349497

  11. Enhanced immune response by amphotericin B following NS1 protein prime-oral recombinant Salmonella vaccine boost vaccination protects mice from dengue virus challenge.

    PubMed

    Liu, Wen-Tssann; Lin, Wei-Ting; Tsai, Chung-Chin; Chuang, Chuan-Chang; Liao, Chin-Len; Lin, Huang-Chi; Hung, Yao-Wen; Huang, Shih-Shiung; Liang, Chung-Chih; Hsu, Hui-Ling; Wang, Hsian-Jenn; Liu, Yu-Tien

    2006-07-26

    A recombinant vaccine strain SL3261/pLT105 of attenuated aroA Salmonella enterica serovar Typhimurium SL3261 strain expressing a secreted dengue virus type 2 non-structural NS1 and Yersinia pestis F1 (Caf1) fusion protein, rNS1:Caf1, was generated. Immunological evaluation was performed by prime-boost vaccine regimen. Oral immunization of mice with 1 x 10(9)cfu of SL3261/pLT105 only induced low levels of NS1-specific antibody response and protective immunity following dengue virus challenge. The parenteral NS1 protein priming-oral Salmonella boosting protocol enhanced both NS1-specific serum IgG response and protective efficacy as compared to mice immunized with each type vaccine alone. Addition of an antifungal antibiotic amphotericin B (AmB) to Salmonella vaccine further enhanced the synergic effects of prime-boost vaccine regimen on the elicited NS1-specific serum IgG response and the protective efficacy. Together, the results demonstrated that the rNS1:Caf1 producing Salmonella SL3261/pLT105 strain fails to provide effective protection as an oral vaccine alone despite co-administration of AmB as an adjuvant capable of enhancing the immune responses, and moreover, the protein priming-oral Salmonella vaccine boosting approach in combination with AmB as an immunization regimen may have the potential to be further explored as an alternative approach for dengue vaccine development. PMID:16759760

  12. Assessing the costs and benefits of an oral vaccine for raccoon rabies: a possible model.

    PubMed

    Meltzer, M I

    1996-01-01

    Any cost-benefit analysis of the use of an oral vaccine to control raccoon rabies should include calculating both costs and benefits in terms of $/unit area. Further, cost savings must be adjusted to match the stages of an epizootic: pre-epizootic, epizootic, and post-epizootic. A generic model, which can be adapted to different sites, illustrates the use of threshold analysis to link distribution costs, cost savings, bait density, and vaccine price. Initial results indicate the need to lower the cost of the vaccine, continue research to determine optimal bait densities, and examine distribution plans that do not require continued protection of areas in which raccoon rabies was eliminated through previous vaccination programs. PMID:8969251

  13. Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells

    PubMed Central

    Kwon, Kwang-Chul; Verma, Dheeraj; Singh, Nameirakpam D.; Herzog, Roland; Daniell, Henry

    2012-01-01

    Among 12 billion injections administered annually, unsafe delivery leads to >20 million infections and >100 million reactions. In an emerging new concept, freeze-dried plant cells (lettuce) expressing vaccine antigens/biopharmaceuticals are protected in the stomach from acids/enzymes but are released to the immune or blood circulatory system when plant cell walls are digested by microbes that colonize the gut. Vaccine antigens bioencapsulated in plant cells upon oral delivery after priming, conferred both mucosal and systemic immunity and protection against bacterial, viral or protozoan pathogens or toxin challenge. Oral delivery of autoantigens was effective against complications of type 1diabetes and hemophilia, by developing tolerance. Oral delivery of proinsulin or exendin-4 expressed in plant cells regulated blood glucose levels similar to injections. Therefore, this new platform offers a low cost alternative to deliver different therapeutic proteins to combat infectious or inherited diseases by eliminating inactivated pathogens, expensive purification, cold storage/transportation and sterile injections. PMID:23099275

  14. Effectiveness of Oral Cholera Vaccine in Haiti: 37-Month Follow-Up.

    PubMed

    Sévère, Karine; Rouzier, Vanessa; Anglade, Stravinsky Benedict; Bertil, Claudin; Joseph, Patrice; Deroncelay, Alexandra; Mabou, Marie Marcelle; Wright, Peter F; Guillaume, Florence Duperval; Pape, Jean William

    2016-05-01

    The first oral cholera vaccine (OCV) campaign, since its prequalification by the World Health Organization, in response to an ongoing cholera epidemic (reactive vaccination) was successfully conducted in a poor urban slum of approximately 70,000 inhabitants in Port-au-Prince, Haiti, in 2012. Vaccine coverage was 75% of the target population. This report documents the impact of OCV in reducing the number of culture-confirmed cases of cholera admitted to the Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) cholera treatment center from that community in the 37 months postvaccination (April 2012-April 30, 2015). Of 1,788 patients with culture-confirmed cholera, 1,770 (99%) were either from outside the vaccine area (1,400 cases) or from the vaccinated community who had not received OCV (370 cases). Of the 388 people from the catchment area who developed culture-confirmed cholera, 370 occurred among the 17,643 people who had not been vaccinated (2.1%) and the remaining 18 occurred among the 52,357 people (0.034%) who had been vaccinated (P < 0.001), for an efficacy that approximates 97.5%. Despite not being designed as a randomized control trial, the very high efficacy is a strong evidence for the effectiveness of OCV as part of an integrated package for the control of cholera in outbreak settings. PMID:26928838

  15. Poliomyelitis in the United States: A Historical Perspective and Current Vaccination Policy.

    ERIC Educational Resources Information Center

    Farizo, Karen M.; And Others

    1990-01-01

    Examines poliomyelitis in the United States by reviewing clinical manifestations and outcomes, history, recent epidemiologic characteristics, characteristics of currently available vaccines, controversies surrounding vaccination policy, current poliovirus vaccination recommendations, and prospects for worldwide eradication. Poliomyelitis remains…

  16. Polio Vaccination

    MedlinePlus

    ... inactive polio vaccine OPV=oral polio vaccine Polio Vaccination Pronounced [PO-lee-oh] Recommend on Facebook Tweet ... handling and storage Related Pages Global Vaccines and Immunization Global Polio Also Known As & Abbreviations Polio=poliomyelitis ...

  17. Evidence for CVD 103-HgR as an effective single-dose oral cholera vaccine.

    PubMed

    Jackson, Sarah S; Chen, Wilbur H

    2015-01-01

    We propose the ideal oral cholera vaccine (OCV) should be an inexpensive, single, oral dose that rapidly confers immunity for a long duration, and is well tolerated by individuals vulnerable to cholera. Vaccine trials in industrialized countries of a single oral dose of 5 × 10(8) colony forming units (CFU) of the live, attenuated cholera strain CVD 103-HgR have shown 88-97% serum vibriocidal antibody seroconversion rates, a correlate of protection and documented vaccine efficacy of ≥80% using volunteer challenge studies with wild-type cholera. For individuals of developing countries, a 5 × 10(9) CFU dose of CVD 103-HgR is necessary to elicit similar antibody responses. Presently, a reformulation of CVD 103-HgR is in late-stage clinical development for prospective US FDA licensure; making a cholera vaccine for US travelers potentially accessible in 2016. The availability of CVD 103-HgR should be a welcome addition to the currently available OCVs. PMID:26228388

  18. Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review

    PubMed Central

    Islam, Mohammad Ariful; Firdous, Jannatul; Choi, Yun-Jaie; Yun, Cheol-Heui; Cho, Chong-Su

    2012-01-01

    Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed. PMID:23271909

  19. Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review.

    PubMed

    Islam, Mohammad Ariful; Firdous, Jannatul; Choi, Yun-Jaie; Yun, Cheol-Heui; Cho, Chong-Su

    2012-01-01

    Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed. PMID:23271909

  20. Immunogenic and antigenic activity of an experimental oral rabies vaccine prepared from the strain Vnukovo-32/107.

    PubMed

    Svrcek, S; Durove, A; Ondrejka, R; Závadová, J; Süliová, J; Benísek, Z; Vrtiak, O J; Feketeová, J; Mad'ar, M

    1995-03-01

    The immunogenic and antigenic activity of an experimental live oral rabies vaccine prepared from the strain Vnukovo-32/107 was evaluated on the basis of results obtained in 3 sets of experiments. These were carried out as model experiments on white mice, then on target animals--red foxes (Vulpes vulpes) and a related species--farm-bred polar foxes (Alopex lagopus). For quantitative determination of the immunogenic activity of the orally or subcutaneously administered rabies vaccines in model experiments on mice a method was used that had been developed in our laboratory. Antibodies were detected and quantified by an ELISA kit that had also been developed in our lab. Tenacity of the experimental vaccine (infectious tissue culture medium after yolk addition) was verified at different temperatures; the effects of storage temperature upon virus titre and immunogenic activity were investigated. An important part of the experiments--evaluation of the antigenic and immunogenic activity of the live vaccine at oral vaccination (vaccination baits, conditions simulating field vaccination) was carried out in foxes. The immunogenic activity (challenge experiments with a street virus on day 180 and 360 after vaccination) was evaluated in common foxes (Vulpes vulpes). The results document a high immunogenic and antigenic activity of the experimental live oral rabies vaccine. The strain Vnukovo-32/107 is suitable for the industrial manufacturing of vaccination baits. In the target species--common foxes challenged on day 180 after primovaccination an 83% protection was observed. Challenge on day 180 after revaccination (or day 360 after primovaccination), the orally immunized foxes proved to be 100% protected. For parallel evaluation of the immunogenic activity of an oral vaccine and for antibody titration it is recommended to employ the quantitative mice test and an ELISA technique, respectively. PMID:7762124

  1. Humoral immune response to oral rabies vaccination in raccoon kits: problems and implications.

    PubMed

    Fry, Tricia L; Vandalen, Kaci K; Shriner, Susan A; Moore, Susan M; Hanlon, Cathleen A; Vercauteren, Kurt C

    2013-06-10

    Little is known about the immunogenicity of RABORAL V-RG(®) (V-RG), an oral rabies vaccine, in raccoon kits (Procyon lotor). The objectives of this study were to characterize the immunogenicity of V-RG in young kits and investigate the potential impact of maternal antibodies on response to vaccination of nursing raccoon kits. Raccoon kits (n=30) were vaccinated at either 3 weeks of age, 7 weeks of age, or assigned as contact controls. Nineteen kits (73%) that were whelped by unvaccinated mothers responded to V-RG exposure (orally or indirect contact) by production of detectable rabies virus neutralizing antibodies (RVNA) while 7 (27%) kits did not respond to V-RG exposure. Four kits were whelped by a mother with high levels of RVNA and all four kits acquired maternal rabies antibodies. At approximately 9 months of age, all kits were inoculated with a killed rabies vaccine, IMRAB3(®). The kits which initially responded to V-RG oral vaccination or contact with vaccinated littermates demonstrated a rapid anamnestic response. In contrast, the V-RG non-responders and those with acquired maternal antibodies exhibited a primary immune response to IMRAB3(®), where RVNA levels were substantially lower on days 5 and 7 than the levels in the animals with an anamnestic response. These findings suggest that the naïve contact kits and the nonresponsive kits most likely remained susceptible to rabies virus infection whereas the ones demonstrating response to V-RG would not have been susceptible to a rabies virus infection. PMID:23602534

  2. Recombinant Saccharomyces cerevisiae serves as novel carrier for oral DNA vaccines in Carassius auratus.

    PubMed

    Yan, Nana; Xu, Kun; Li, Xinyi; Liu, Yuwan; Bai, Yichun; Zhang, Xiaohan; Han, Baoquan; Chen, Zhilong; Zhang, Zhiying

    2015-12-01

    Oral delivery of DNA vaccines represents a promising vaccinating method for fish. Recombinant yeast has been proved to be a safe carrier for delivering antigen proteins and DNAs to some species in vivo. However, whether recombinant yeast can be used to deliver functional DNAs for vaccination to fish is still unknown. In this study, red crucian carp (Carassius auratus) was orally administrated with recombinant Saccharomyces cerevisiae harboring CMV-EGFP expression cassette. On day 5 post the first vaccination, EGFP expression in the hindgut was detected under fluorescence microscope. To further study whether the delivered gene could induce specific immune responses, the model antigen ovalbumin (OVA) was used as immunogen, and oral administrations were conducted with recombinant S. cerevisiae harboring pCMV-OVA mammalian gene expression cassette as gene delivery or pADH1-OVA yeast gene expression cassette as protein delivery. Each administration was performed with three different doses, and the OVA-specific serum antibody was detected in all the experimental groups by western blotting and enzyme-linked immunosorbent assay (ELISA). ELISA assay also revealed that pCMV-OVA group with lower dose (pCMV-OVA-L) and pADH1-OVA group with moderate dose (pADH1-OVA-M) triggered relatively stronger antibody response than the other two doses. Moreover, the antibody level induced by pCMV-OVA-L group was significantly higher than pADH1-OVA-M group at the same serum dilutions. All the results suggested that recombinant yeast can be used as a potential carrier for oral DNA vaccines and would help to develop more practical strategies to control infectious diseases in aquaculture. PMID:26481518

  3. Uptake of oral rotavirus vaccine and timeliness of routine immunization in Brazil’s National Immunization Program

    PubMed Central

    Flannery, Brendan; Samad, Samia; de Moraes, José Cássio; Tate, Jacqueline E.; Danovaro-Holliday, M. Carolina; de Oliveira, Lúcia Helena; Rainey, Jeanette J.

    2015-01-01

    Introduction In March, 2006, oral rotavirus vaccine was added to Brazil’s infant immunization schedule with recommended upper age limits for initiating (by age 14 weeks) and completing (by age 24 weeks) the two-dose series to minimize age-specific risk of intussusception following rotavirus vaccination. Several years after introduction, estimated coverage with rotavirus vaccine (83%) was lower compared to coverage for other recommended childhood immunizations (≥94%). Methods We analyzed data from Brazil’s national immunization program on uptake of oral rotavirus vaccine by geographic region and compared administrative coverage estimates for first and second doses of oral rotavirus vaccine (Rota1 and Rota2) with first and second doses of diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP-Hib1 and DTP-Hib2). For 27 Brazilian cities, we compared differences between estimated rotavirus and DTP-Hib coverage in 2010 with delayed receipt of DTP-Hib vaccine among a cohort of children surveyed before rotavirus introduction. Results In 2010, infant vaccination coverage was 99.0% for DTP-Hib1 versus 95.2% for Rota1 (3.8% difference), and 98.4% for DTP-Hib2 versus 83.0% for Rota2 (15.4% difference), with substantial regional variation. Differences between DTP-Hib and rotavirus vaccination coverage in Brazilian cities correlated with delay in DTP-Hib vaccination among children surveyed. Age restrictions for initiating and completing the rotavirus vaccination series likely contributed to lower coverage with rotavirus vaccine in Brazil. Conclusion To maximize benefits of rotavirus vaccination, strategies are needed to improve timeliness of routine immunizations; monitoring rotavirus vaccine uptake and intussusception risk is needed to guide further recommendations for rotavirus vaccination. PMID:23313652

  4. Vaccine-associated paralytic poliomyelitis and BCG-osis in an immigrant child with severe combined immunodeficiency syndrome - Texas, 2013.

    PubMed

    Trimble, Robert; Atkins, Jane; Quigg, Troy C; Burns, Cara C; Wallace, Gregory S; Thomas, Mary; Mangla, Anil T; Infante, Anthony J

    2014-08-22

    Poliovirus transmission has been eliminated in most of the world through the use of inactivated poliovirus vaccine (IPV) and live, attenuated oral poliovirus vaccine (OPV). In the United States, use of OPV was discontinued by the year 2000 because of the potential for vaccine-associated paralytic polio (VAPP); an average of eight cases were reported each year in the United States during 1980-2000. Polio eradication efforts in other parts of the world continue to rely on OPV to take advantage of transmission of poliovirus vaccine strains to unvaccinated persons in the population, lower cost, and ease of administration. In 2013, an infant aged 7 months who recently immigrated to the United States from India was referred to a hospital in San Antonio, Texas. The infant had fever, an enlarging skin lesion in the deltoid region with axillary lymphadenopathy, decreased activity, and inability to bear weight on the left leg, progressing to paralysis of the left leg over a 6-week period. Recognition of lymphopenia on complete blood count led to immune evaluation, which revealed the presence of severe combined immunodeficiency syndrome (SCIDS), an inherited disorder. A history of OPV and bacille Calmette-Guérin (BCG) vaccination in India led to the diagnoses of VAPP and BCG-osis, which were confirmed microbiologically. This report demonstrates the importance of obtaining a comprehensive clinical history in a child who has recently immigrated to the United States, with recognition that differing vaccine practices in other countries might require additional consideration of potential etiologies. PMID:25144542

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

    PubMed

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

    2008-06-19

    The elimination of rabies from the red fox (Vulpes vulpes) in Western Europe has been achieved by the oral rabies vaccination (ORV) of wildlife with a range of attenuated rabies virus strains. With the exception of the vaccinia rabies glycoprotein recombinant vaccine (VRG), all strains were originally derived from a common ancestor; the Street Alabama Dufferin (SAD) field strain. However, after more than 30 years of ORV it is still not possible to distinguish these vaccine strains and there is little information on the genetic basis for their attenuation. We therefore sequenced and compared the full-length genome of five commercially available SAD vaccine viruses (SAD B19, SAD P5/88, SAG2, SAD VA1 and SAD Bern) and four other SAD strains (the original SAD Bern, SAD VA1, ERA and SAD 1-3670 Wistar). Nucleotide sequencing allowed identifying each vaccine strain unambiguously. Phylogenetic analysis revealed that the majority of the currently used commercial attenuated rabies virus vaccines appear to be derived from SAD B19 rather than from SAD Bern. One commercially available vaccine virus did not contain the SAD strain mentioned in the product information of the producer. Two SAD vaccine strains appeared to consist of mixed genomic sequences. Furthermore, in-del events targeting A-rich sequences (in positive strand) within the 3' non-coding regions of M and G genes were observed in SAD-derivates developed in Europe. Our data also supports the idea of a possible recombination that had occurred during the derivation of the European branch of SAD viruses. If confirmed, this recombination event would be the first one reported among RABV vaccine strains. PMID:18485548

  6. Innovative IPV from attenuated Sabin poliovirus or newly designed alternative seed strains.

    PubMed

    Hamidi, Ahd; Bakker, Wilfried A M

    2012-11-01

    This article gives an overview of the patent literature related to innovative inactivated polio vaccine (i-IPV) based on using Sabin poliovirus strains and newly developed alternative recombinant poliovirus strains. This innovative approach for IPV manufacturing is considered to attribute to the requirement for affordable IPV in the post-polio-eradication era, which is on the horizon. Although IPV is a well-established vaccine, the number of patent applications in this field was seen to have significantly increased in the past decade. Currently, regular IPV appears to be too expensive for universal use. Future affordability may be achieved by using alternative cell lines, alternative virus seed strains, improved and optimized processes, dose sparing, or the use of adjuvants. A relatively short-term option to achieve cost-price reduction is to work on regular IPV, using wild-type poliovirus strains, or on Sabin-IPV, based on using attenuated poliovirus strains. This price reduction can be achieved by introducing efficiency in processing. There are also multiple opportunities to work on dose sparing, for example, by using adjuvants or fractional doses. Renewed interest in this field was clearly reflected in the number and diversity of patent applications. In a later stage, several innovative approaches may become even more attractive, for example the use of recombinant virus strains or even a totally synthetic vaccine. Currently, such work is mainly carried out by research institutes and universities and therefore clinical data are not available. PMID:24236927

  7. Oral vaccination of captive small Indian mongoose (Herpestes auropunctatus) against rabies.

    PubMed

    Vos, Ad; Kretzschmar, Antje; Ortmann, Steffen; Lojkic, Ivana; Habla, Christiane; Müller, Thomas; Kaiser, Christian; Hundt, Boris; Schuster, Peter

    2013-10-01

    The small Indian mongoose (Herpestes auropunctatus), a rabies reservoir species on several Islands in the Caribbean, was successfully immunized against rabies for the first time by offering animals a vaccine bait specifically designed for this small carnivore. The bait contained on average 0.6 mL of the genetically modified replication-competent rabies virus construct SPBN GASGAS (10(8.5) focus-forming units/mL). Three of four mongooses offered a bait developed an immune response above 0.5 IU/mL, but the response was less pronounced than in two animals offered the vaccine by direct oral instillation. PMID:24502736

  8. Exploring the role of environmental enteropathy in malnutrition, infant development and oral vaccine response

    PubMed Central

    Gilmartin, Allissia A.; Petri, William A.

    2015-01-01

    Environmental enteropathy (EE) is a poorly defined state of intestinal inflammation without overt diarrhoea that occurs in individuals exposed over time to poor sanitation and hygiene. It is characterized pathologically by small intestine villous blunting and inflammation. In children from low-income countries, it is implicated as a cause of malnutrition, oral vaccine failure and impaired cognitive development. Here we review the search for non-invasive biomarkers to measure EE non-invasively, and assess the current evidence linking EE to malnutrition, vaccine failure and neurocognitive development. PMID:25964455

  9. Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination

    PubMed Central

    Derbise, Anne; Hanada, Yuri; Khalifé, Manal; Carniel, Elisabeth; Demeure, Christian E.

    2015-01-01

    Background No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably. Methodology/Principal Findings The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1—Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis. Significance VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection

  10. HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions

    PubMed Central

    TESTI, D.; NARDONE, M.; MELONE, P.; CARDELLI, P.; OTTRIA, L.; ARCURI, C.

    2015-01-01

    SUMMARY The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%–90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before “sexual puberty”. The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer. PMID:27555904

  11. HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions.

    PubMed

    Testi, D; Nardone, M; Melone, P; Cardelli, P; Ottria, L; Arcuri, C

    2015-01-01

    The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer. PMID:27555904

  12. Twenty year experience of the oral rabies vaccine SAG2 in wildlife: a global review.

    PubMed

    Mähl, Philippe; Cliquet, Florence; Guiot, Anne-Laure; Niin, Enel; Fournials, Emma; Saint-Jean, Nathalie; Aubert, Michel; Rupprecht, Charles E; Gueguen, Sylvie

    2014-01-01

    The SAG2 vaccine (RABIGEN® SAG2) is a modified live attenuated rabies virus vaccine, selected from the SAD Bern strain in a two-step process of amino acid mutation using neutralizing monoclonal antibodies. The strain is genetically stable and does not spread in vivo or induce a persistent infection. Its absence of residual pathogenicity was extensively demonstrated in multiple target and non target species (such as wild carnivores and rodent species), including non-human primates. The efficacy of SAG2 baits was demonstrated according to the EU requirements for the red fox and raccoon dog. The use of safe and potent rabies vaccines such as SAG2 largely contributed to the elimination of rabies in Estonia, France, Italy and Switzerland. Importantly, these countries were declared free of rabies after few years of oral vaccination campaigns with SAG2 baits distributed with an appropriate strategy. The excellent tolerance of the SAG2 vaccine has been confirmed in the field since its first use in 1993. No safety issues have been reported, and in particular no vaccine-induced rabies cases were diagnosed, after the distribution of more than 20 million SAG2 baits in Europe. PMID:25106552

  13. Social and cultural determinants of oral cholera vaccine uptake in Zanzibar.

    PubMed

    Schaetti, Christian; Ali, Said M; Hutubessy, Raymond; Khatib, Ahmed M; Chaignat, Claire-Lise; Weiss, Mitchell G

    2012-09-01

    Effectiveness of mass cholera vaccination campaigns requires not only technical and financial capacity but also consideration of social and cultural factors affecting vaccine acceptance. This study examined the influence of local community views of cholera on oral cholera vaccine (OCV) uptake in a mass vaccination campaign in 2009 in peri-urban and rural areas of Zanzibar. It used data from interviews conducted before the campaign and followed previous research assessing determinants of anticipated OCV acceptance. OCV uptake was lower than the reported anticipated acceptance. Less than half of the 356 adult respondents (49.7%) drank the required two doses of OCV. Variables referring to socio-cultural features of diarrheal illness that respondents identified with a cholera case vignette explained uptake better than analysis only of socio-demographic characteristics. Somatic features of illness not specific for cholera were negative determinants. Recognition of unconsciousness as a serious sign of dehydration and concern that cholera outbreaks would overwhelm the local healthcare system in the rural area were positive determinants of acceptance. Female gender, rural residence and older age were also positive determinants of OCV uptake. For further vaccine action with OCVs, cholera as a cause of severe dehydration should be distinguished from other causes of diarrhea. Planning should acknowledge rural concern about the relationship of limited capacity of the healthcare system to cope with cholera outbreaks and the priority of a cholera vaccine. Findings recommend particular efforts to increase cholera immunization coverage among young adults, in peri-urban areas and for men. PMID:22894965

  14. Adaptation of the WHO guideline for residual DNA in parenteral vaccines produced on continuous cell lines to a limit for oral vaccines.

    PubMed

    Lebron, J A; Troilol, P J; Pacchione, S; Griffiths, T G; Harper, L B; Mixson, L A; Jackson, B E; Michna, L; Barnum, A B; Denisova, L; Johnson, C N; Maurer, K L; Morgan-Hoffman, S; Niu, Z; Roden, D F; Wang, Z; Wolf, J J; Hamilton, T R; Laux, K M; Soper, K A; Ledwith, B J

    2006-01-01

    Although there is a WHO guidance for a limit on residual DNA for parenterally administered vaccines produced on continuous cell lines, there is no corresponding guidance for oral vaccines. To help determine an oral limit, we performed a study of Vero cell DNA uptake in rats, in which the relative uptake and persistence of Vero cell DNA administered orally was compared to its uptake when delivered intramuscularly (IM). The results of this study allowed the generation of an empirically derived IM versus oral factor (10(6)) representing the relative inefficiency of DNA uptake by oral administration. This factor was then applied to the WHO recommended parenteral limit of 10 ng/dose to determine a corresponding upper limit on the level of residual Vero cell DNA for an oral vaccine of 10 mg. As a conservative approach, this empirically determined limit was reduced 100-fold to 100 microg. Thus, the results of this animal study, together with additional evidence in the literature, support a residual DNA safety limit of 100 microg per dose for an oral vaccine produced on a continuous cell line. PMID:16566435

  15. An oral Mycobacterium bovis BCG vaccine for wildlife produced in the absence of animal-derived reagents.

    PubMed

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2009-09-01

    Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products. PMID:19571109

  16. The Corn Smut ('Huitlacoche') as a New Platform for Oral Vaccines.

    PubMed

    Juárez-Montiel, Margarita; Romero-Maldonado, Andrea; Monreal-Escalante, Elizabeth; Becerra-Flora, Alicia; Korban, Schuyler S; Rosales-Mendoza, Sergio; Jiménez-Bremont, Juan Francisco

    2015-01-01

    The development of new alternative platforms for subunit vaccine production is a priority in the biomedical field. In this study, Ustilago maydis, the causal agent of common corn smut or 'huitlacoche'has been genetically engineered to assess expression and immunogenicity of the B subunit of the cholera toxin (CTB), a relevant immunomodulatory agent in vaccinology. An oligomeric CTB recombinant protein was expressed in corn smut galls at levels of up to 1.3 mg g-1 dry weight (0.8% of the total soluble protein). Mice orally immunized with 'huitlacoche'-derived CTB showed significant humoral responses that were well-correlated with protection against challenge with the cholera toxin (CT). These findings demonstrate the feasibility of using edible corn smut as a safe, effective, and low-cost platform for production and delivery of a subunit oral vaccine. The implications of this platform in the area of molecular pharming are discussed. PMID:26207365

  17. The Corn Smut (‘Huitlacoche’) as a New Platform for Oral Vaccines

    PubMed Central

    Juárez-Montiel, Margarita; Romero-Maldonado, Andrea; Monreal-Escalante, Elizabeth; Becerra-Flora, Alicia; Korban, Schuyler S.; Rosales-Mendoza, Sergio; Jiménez-Bremont, Juan Francisco

    2015-01-01

    The development of new alternative platforms for subunit vaccine production is a priority in the biomedical field. In this study, Ustilago maydis, the causal agent of common corn smut or ‘huitlacoche’has been genetically engineered to assess expression and immunogenicity of the B subunit of the cholera toxin (CTB), a relevant immunomodulatory agent in vaccinology. An oligomeric CTB recombinant protein was expressed in corn smut galls at levels of up to 1.3 mg g-1 dry weight (0.8% of the total soluble protein). Mice orally immunized with ‘huitlacoche’-derived CTB showed significant humoral responses that were well-correlated with protection against challenge with the cholera toxin (CT). These findings demonstrate the feasibility of using edible corn smut as a safe, effective, and low-cost platform for production and delivery of a subunit oral vaccine. The implications of this platform in the area of molecular pharming are discussed. PMID:26207365

  18. Oral rabies vaccination of red foxes and golden jackals in Israel: preliminary bait evaluation.

    PubMed

    Linhart, S B; King, R; Zamir, S; Naveh, U; Davidson, M; Perl, S

    1997-12-01

    Field trials were conducted in late April to early May of 1995 and 1996 in central Israel to assess the potential for controlling rabies in red foxes (Vulpes vulpes) and golden jackals (Canis aureus) by using vaccine-laden baits. Of the bait types which were field tested, polymer fish meal baits were selected as the most suitable for both species. Fish meal baits containing tetracycline hydrochloride, an oral biomarker, were distributed by four-wheel-drive vehicle at a density of approximately 30 baits/km2 in two test areas of 35 km2. Of the animals which were trapped and euthanized seven to ten days after treatment, 65% of foxes and 56% of jackals gave positive results when tested for the biomarker. These results indicate the potential effectiveness of oral rabies vaccination of these species in Israel and possibly elsewhere in the Middle East, where rabies is a problem in wild canids. PMID:9567312

  19. Systemic, nasal and oral live vaccines against Pseudomonas aeruginosa: a clinical trial of immunogenicity in lower airways of human volunteers.

    PubMed

    Bumann, Dirk; Behre, Christoph; Behre, Katharina; Herz, Steffen; Gewecke, Britta; Gessner, J Engelbert; von Specht, Bernd Ulrich; Baumann, Ulrich

    2010-01-01

    Vaccination against Pseudomonas aeruginosa is a desirable, yet challenging strategy for prevention of airway infection in patients with cystic fibrosis. We compared the formation of antibodies in lower airways induced by systemic and mucosal vaccination strategies. We immunised 48 volunteers in six vaccination groups with either a systemic, a nasal, or four newly constructed oral live vaccines based on attenuated live Salmonella (strains CVD908 and Ty21a), followed by a systemic booster vaccination. All vaccines were based on a recombinant fusion protein of the highly conserved P. aeruginosa outer membrane proteins OprF and OprI as antigen. While systemic and mucosal vaccines induced a comparable rise of serum antibody titers, a significant rise of IgA and IgG antibodies in the lower airways was noted only after nasal and oral vaccinations. We conclude that nasal and oral OprF-OprI vaccines are promising candidates for development of antipseudomonal immunisation through inducing a specific antibody response in the lung. PMID:19887136

  20. Clinical Trial of an Oral Live Shigella sonnei Vaccine Candidate, WRSS1, in Thai Adults

    PubMed Central

    Islam, Dilara; Chamnanchanunt, Supat; Ruamsap, Nattaya; Khantapura, Patchariya; Kaewkungwal, Jaranit; Kittitrakul, Chatporn; Luvira, Viravarn; Dhitavat, Jittima; Venkatesan, Malabi M.; Mason, Carl J.; Bodhidatta, Ladaporn

    2016-01-01

    Live attenuated Shigella sonnei vaccine candidate WRSS1, previously tested in U.S. and Israeli volunteers, was evaluated in a population of adult Thai volunteers in which the organism is endemic. In a randomized placebo-controlled, double-blind design, inpatient participants received a single oral dose of 1.6 × 104 CFU of WRSS1. The vaccine was generally well tolerated, with equal numbers of vaccinees and placebo controls showing mild symptoms. Only 3 of 13 vaccinees (23%) had culture-positive stools, while a total of 9 vaccinees were positive by PCR. Lack of vaccine shedding in volunteers correlated with lack of clinical symptoms and immune responses, just as the duration of fecal shedding correlated directly with stronger immune responses. Two months following immunization, 10 vaccinees and 10 newly recruited naive controls received a challenge dose of 1,670 CFU of virulent S. sonnei strain 53G. This dose had previously demonstrated a 75% attack rate for dysentery in Thai volunteers. However, in this study the attack rate for dysentery in naive controls after challenge was 20%. Based on clinical record summaries, 3 vaccinees and 5 naive controls experienced clinically relevant illness (diarrhea/dysentery/fever/shigellosis), and a 40% vaccine efficacy was calculated. When these data are compared to those for the performance of this vaccine candidate in more naive populations, it is clear that a single oral dose of WRSS1 at 104 CFU failed to achieve its full potential in a population in which the organism is endemic. Higher doses and/or repeated immunizations may contribute to improved vaccine shedding and consequent elevation of protective immune responses in a population in which the organism is endemic. (The study has been registered at ClinicalTrials.gov under registration no. NCT01080716.) PMID:27146000

  1. Clinical Trial of an Oral Live Shigella sonnei Vaccine Candidate, WRSS1, in Thai Adults.

    PubMed

    Pitisuttithum, Punnee; Islam, Dilara; Chamnanchanunt, Supat; Ruamsap, Nattaya; Khantapura, Patchariya; Kaewkungwal, Jaranit; Kittitrakul, Chatporn; Luvira, Viravarn; Dhitavat, Jittima; Venkatesan, Malabi M; Mason, Carl J; Bodhidatta, Ladaporn

    2016-07-01

    Live attenuated Shigella sonnei vaccine candidate WRSS1, previously tested in U.S. and Israeli volunteers, was evaluated in a population of adult Thai volunteers in which the organism is endemic. In a randomized placebo-controlled, double-blind design, inpatient participants received a single oral dose of 1.6 × 10(4) CFU of WRSS1. The vaccine was generally well tolerated, with equal numbers of vaccinees and placebo controls showing mild symptoms. Only 3 of 13 vaccinees (23%) had culture-positive stools, while a total of 9 vaccinees were positive by PCR. Lack of vaccine shedding in volunteers correlated with lack of clinical symptoms and immune responses, just as the duration of fecal shedding correlated directly with stronger immune responses. Two months following immunization, 10 vaccinees and 10 newly recruited naive controls received a challenge dose of 1,670 CFU of virulent S. sonnei strain 53G. This dose had previously demonstrated a 75% attack rate for dysentery in Thai volunteers. However, in this study the attack rate for dysentery in naive controls after challenge was 20%. Based on clinical record summaries, 3 vaccinees and 5 naive controls experienced clinically relevant illness (diarrhea/dysentery/fever/shigellosis), and a 40% vaccine efficacy was calculated. When these data are compared to those for the performance of this vaccine candidate in more naive populations, it is clear that a single oral dose of WRSS1 at 10(4) CFU failed to achieve its full potential in a population in which the organism is endemic. Higher doses and/or repeated immunizations may contribute to improved vaccine shedding and consequent elevation of protective immune responses in a population in which the organism is endemic. (The study has been registered at ClinicalTrials.gov under registration no. NCT01080716.). PMID:27146000

  2. Evaluation of the first oral rabies vaccination campaign of the red foxes in Greece.

    PubMed

    Korou, Laskarina-Maria; Tasioudi, Konstantia E; Tzani, Myrsini; Konstantinidis, Athanasios; Plevraki, Aikaterini; Iliadou, Peristera; Kostoglou, Petroula; Kaimaras, Dimitrios; Doudounakis, Spyridon; Mangana-Vougiouka, Olga

    2016-01-01

    Following the late 2012 recurrence of rabies in wild foxes (Vulpes vulpes) in central and north-western Greece, the first oral fox vaccination campaign co-financed by the European Union (EU) and the Greek state budget, was implemented. Initially, it involved 24 regional units of the Greek territory during the period October-December 2013. Vaccine-baits were aerially distributed by fixed-wing aircrafts. Vaccines were scattered along parallel flight paths 500m apart in order to optimize aerial missions and achieve homogeneous distribution. A geographical information system was used to objectively evaluate bait distribution. This system identified areas of inadequate bait density that would require additional flights. A total number of 1,504,821 baits were distributed covering an area of 54,584.29km(2). To assess the effectiveness of oral vaccination campaign a monitoring program was introduced, which entailed examination of serum samples and canine teeth derived from red foxes collected in the field. The laboratory analysis revealed 60% seropositivity and detection of tetracycline biomarker in 70% of the foxes tested. PMID:26616552

  3. Nest box-deployed bait for delivering oral vaccines to white-footed mice

    PubMed Central

    Telford, Sam R.; Cunningham, Jenny A.; Waltari, Eric; Hu, Linden

    2014-01-01

    Although a wide range of interventions are available for use in reducing the public health burden of Lyme disease, additional tools are needed. Vaccinating mouse reservoirs may reduce the prevalence of spirochetal infection due to the powerful vector and reservoir competence-modulating effects of anti-outer surface protein A (OspA) antibody. A delivery system for an oral immunogen would be required for field trials of any candidate vaccine. Accordingly, we tested candidate bait preparations that were designed to be environmentally stable, attractive to mice, and non-nutritive. In addition, we determined whether delivery of such baits within nest boxes could effectively target white-footed mice. A peanut butter-scented bait was preferred by mice over a blueberry-scented one. At a deployment rate of 12.5 nest boxes per hectare, more than half of resident mice ingested a rhodamine-containing bait, as demonstrated by fluorescent staining of their vibrissae. We conclude that a peanut butter-scented hardened bait placed within simple wood nest boxes would effectively deliver vaccine to white-footed mice, thereby providing baseline information critical for designing field trials of a candidate oral vaccine. PMID:21890068

  4. A field trial to determine the feasibility of delivering oral vaccines to wild swine.

    PubMed

    Fletcher, W O; Creekmore, T E; Smith, M S; Nettles, V F

    1990-10-01

    A field study was conducted on Ossabaw Island, Georgia (USA) to determine the feasibility of delivering oral vaccines to wild swine (Sus scrofa). Baits were made of polymerbound fish meal and contained a gelatin capsule as a potential vaccine chamber. Two biomarkers, iophenoxic acid and tetracycline, were incorporated into each bait, and soured chicken mash was used as an attractant. Baits (n = 1,980) were distributed in a grid pattern on a 405-ha test site and monitored for animal disturbance. Within 72 hr, 88% of 393 monitored baits were gone, and observations of track-beds surrounding 100 baits indicated that at least 52% were taken by wild swine. Subsequent testing of 80 wild swine for the biomarkers revealed that 95% of the animals had consumed bait. Track-bed observations indicated that raccoons (Procyon lotor) were the only non-target animal that frequently took baits. Biomarker analyses indicated 44% of 16 raccoons tested had eaten bait. It was concluded that oral vaccine delivery to wild swine should be considered as a feasible method of control or eradication of pseudorabies and/or swine brucellosis in wild swine if effective vaccines become available. PMID:2174467

  5. A novel adjuvanted capsule based strategy for oral vaccination against infectious diarrhoeal pathogens.

    PubMed

    Davitt, Christopher J H; McNeela, Edel A; Longet, Stephanie; Tobias, Joshua; Aversa, Vincenzo; McEntee, Craig P; Rosa, Monica; Coulter, Ivan S; Holmgren, Jan; Lavelle, Ed C

    2016-07-10

    Diarrhoeal infections are a major cause of morbidity and mortality with enterotoxigenic Escherichia coli (ETEC) and cholera imposing a significant global burden. There is currently no licensed vaccine for ETEC. Development of new nonliving oral vaccines has proven difficult due to the physicochemical and immunological challenges associated with the oral route. This demands innovative delivery solutions to protect antigens, control their release and build in immune-stimulatory activity. We describe the Single Multiple Pill® (SmPill®) vaccine formulation which combines the benefits of enteric polymer coating to protect against low gastric pH, a dispersed phase to control release and aid the solubility of non-polar components and an optimized combination of adjuvant and antigen to promote mucosal immunity. We demonstrate the effectiveness of this system with whole cell killed E. coli overexpressing colonization factor antigen I (CFA/I), JT-49. Alpha-galactosylceramide was identified as a potent adjuvant within SmPill® that enhanced the immunogenicity of JT-49. The bacteria associated with the dispersed phase were retained within the capsules at gastric pH but released at intestinal pH. Vaccination with an optimized SmPill® formulation promoted CFA/I-specific immunoglobulin A (IgA) responses in the intestinal mucosa in addition to serum IgG and a solubilized adjuvant was indispensable for efficacy. PMID:27157995

  6. A lipid based multi-compartmental system: Liposomes-in-double emulsion for oral vaccine delivery.

    PubMed

    Liau, Jin Jau; Hook, Sarah; Prestidge, Clive A; Barnes, Timothy J

    2015-11-01

    The gastric mucosa provides the entry point for the majority of pathogens, as well as being the induction site for protective immunity; however, there remain few examples of oral vaccines due to the challenges presented by the gastrointestinal route. In this study, we develop a lipid-based multi-compartmental system for oral vaccine delivery. Specifically, we have optimised the formulation of a water-in-oil-in-water double emulsion prepared from a triglyceride - soya bean oil, using surfactants Span 80/Tween 80 and Pluronic F127 to stabilise the internal and external water phases, respectively. Into the internal water phase, we also incorporated a PEGylated liposome, prepared using hydrogenated phosphatidyl choline as a carrier for our model protein, FITC-labelled ovalbumin. We demonstrated the successful incorporation of intact liposomes into the internal water phase of the double emulsion using imaging techniques including cryo-SEM and confocal microscopy. Finally, we use in vitro release studies of FITC-ovalbumin, to provide further confirmation of the multi-compartmental structure of the double emulsion system and demonstrate significant extended release of the entrapped model antigen compared with PEG-liposomes; these characteristics are attractive for oral vaccine delivery. PMID:26455337

  7. Identification and Manipulation of the Molecular Determinants Influencing Poliovirus Recombination

    PubMed Central

    Runckel, Charles; Westesson, Oscar; Andino, Raul; DeRisi, Joseph L.

    2013-01-01

    The control and prevention of communicable disease is directly impacted by the genetic mutability of the underlying etiological agents. In the case of RNA viruses, genetic recombination may impact public health by facilitating the generation of new viral strains with altered phenotypes and by compromising the genetic stability of live attenuated vaccines. The landscape of homologous recombination within a given RNA viral genome is thought to be influenced by several factors; however, a complete understanding of the genetic determinants of recombination is lacking. Here, we utilize gene synthesis and deep sequencing to create a detailed recombination map of the poliovirus 1 coding region. We identified over 50 thousand breakpoints throughout the genome, and we show the majority of breakpoints to be concentrated in a small number of specific “hotspots,” including those associated with known or predicted RNA secondary structures. Nucleotide base composition was also found to be associated with recombination frequency, suggesting that recombination is modulated across the genome by predictable and alterable motifs. We tested the predictive utility of the nucleotide base composition association by generating an artificial hotspot in the poliovirus genome. Our results imply that modification of these motifs could be extended to whole genome re-designs for the development of recombination-deficient, genetically stable live vaccine strains. PMID:23408891

  8. Oral vaccination with lipid-formulated BCG induces a long-lived, multifunctional CD4(+) T cell memory immune response.

    PubMed

    Ancelet, Lindsay R; Aldwell, Frank E; Rich, Fenella J; Kirman, Joanna R

    2012-01-01

    Oral delivery of BCG in a lipid formulation (Liporale™-BCG) targets delivery of viable bacilli to the mesenteric lymph nodes and confers protection against an aerosol Mycobacterium tuberculosis challenge. The magnitude, quality and duration of the effector and memory immune response induced by Liporale™-BCG vaccination is unknown. Therefore, we compared the effector and memory CD4(+) T cell response in the spleen and lungs of mice vaccinated with Liporale™-BCG to the response induced by subcutaneous BCG vaccination. Liporale™-BCG vaccination induced a long-lived CD4(+) T cell response, evident by the detection of effector CD4(+) T cells in the lungs and a significant increase in the number of Ag85B tetramer-specific CD4(+) T cells in the spleen up to 30 weeks post vaccination. Moreover, following polyclonal stimulation, Liporale™-BCG vaccination, but not s.c. BCG vaccination, induced a significant increase in both the percentage of CD4(+) T cells in the lungs capable of producing IFNγ and the number of multifunctional CD4(+) T cells in the lungs at 30 weeks post vaccination. These results demonstrate that orally delivered Liporale™-BCG vaccine induces a long-lived multifunctional immune response, and could therefore represent a practical and effective means of delivering novel BCG-based TB vaccines. PMID:23049885

  9. Relaxation of purifying selection on the SAD lineage of live attenuated oral vaccines for rabies virus.

    PubMed

    Hughes, Austin L

    2009-09-01

    Analysis of patterns of nucleotide sequence diversity in wild-type rabies virus (RABV) genomes and in the SAD live attenuated oral vaccine lineage was used to test for the relaxation of purifying selection in the latter and provide evidence regarding the genomic regions where such relaxation of selection occurs. The wild-type sequences showed evidence of strong past and ongoing purifying selection both on nonsynonymous sites in coding regions and on non-coding regions, particularly the start, end and 5' UTR regions. SAD vaccine sequences showed a relaxation of purifying selection at nonsynonymous sites in coding regions, resulting a substantial number of amino acid sequence polymorphisms at sites that were invariant in the wild-type sequences. Moreover, SAD vaccine sequences showed high levels of mutation accumulation in the non-coding regions that were most conserved in the wild-type sequences. Understanding the biological effects of the unique mutations accumulated in the vaccine lineage is important because of their potential effects on antigenicity and effectiveness of the vaccine. PMID:19409512

  10. Relaxation of Purifying Selection on the SAD Lineage of Live Attenuated Oral Vaccines for Rabies Virus

    PubMed Central

    Hughes, Austin L.

    2009-01-01

    Analysis of patterns of nucleotide sequence diversity in wild-type rabies virus (RABV) genomes and in the SAD live attenuated oral vaccine lineage was used to test for the relaxation of purifying selection in the latter and provide evidence regarding the genomic regions where such relaxation of selection occurs. The wild-type sequences showed evidence of strong past and ongoing purifying selection both on non-synonymous sites in coding regions and on non-coding regions, particularly the start and end and 5’ UTR regions. SAD vaccine sequences showed a relaxation of purifying selection at nonsynonymous sites in coding regions, resulting a substantial number of amino acid sequence polymorphisms at sites that were invariant in the wild-type sequences. Moreover, SAD vaccine sequences showed high levels of mutation accumulation in the non-coding regions that were most conserved in the wild-type sequences. Understanding the biological effects of the unique mutations accumulated in the vaccine lineage is important because of their potential effects on antigenicity and effectiveness of the vaccine. PMID:19409512