Vaccine (VACCINE)

Publications in this journal

• Article: Kinetics of the inflammatory response following intramuscular injection of aluminum adjuvant.

  Fangjia Lu, Harm Hogenesch
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  ABSTRACT: Aluminum-containing adjuvants are widely used in human and veterinary vaccines, but their mechanism of action is not well understood. Recent evidence suggests an important role for inflammation in the immune response to aluminum-adjuvanted vaccines. To better understand this process, vaccines with aluminum adjuvant were injected into naïve or previously immunized mice and the injection sites were characterized for the corresponding primary and secondary inflammatory response at different time points after immunization. Inflammatory cells appeared at the injection site between 2h and 6h after vaccination, dominated by neutrophils at first, followed by macrophages, and later eosinophils and MHCII(+) cells. The number of cells at the injection site increased over time, except neutrophils, which decreased in number after day 2. There was extensive phagocytosis of aluminum adjuvant particles by macrophages. In secondary immunized mice, a faster and more robust recruitment of eosinophils, macrophages, and antigen presenting cells was observed at the injection site. The enhanced recruitment of inflammatory cells in previously immunized mice coincided with increased expression of relevant chemokines at the injection site. Since neutrophils accumulated first in response to aluminum-adjuvanted vaccines, their role was evaluated by depleting them prior to vaccination. Neutrophil depletion transiently reduced the recruitment of macrophages but it did not change the recruitment of eosinophils and MHCII(+) cells or the quality and magnitude of the antibody response.
  Vaccine 06/2013;
• Article: Review of hepatitis B surveillance in China: Improving information to frame future directions in prevention and control.

  Fuqiang Cui, Jan Drobeniuc, Steve Hadler, Yvan J Hutin, Fubao Ma, Steve Wiersma, Fuzhen Wang, Jiang Wu, Hui Zheng, Liwei Zhou, Shuyan Zuo
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  ABSTRACT: BACKGROUND: As the WHO verified that China reached the target of 1% prevalence of chronic hepatitis B infection among children targeted by universal hepatitis B immunization of newborns, the country considered new options for hepatitis B prevention and control. We reviewed hepatitis B surveillance in the broader context of viral hepatitis surveillance to propose recommendations to improve the system. METHODS: We described surveillance for viral hepatitis in China with a specific focus on hepatitis B. We assessed critical attributes of the system, including data quality, predictive positive value and usefulness. RESULTS: While remarkable progress in hepatitis B immunization of infants and children has likely almost eliminated transmission in younger age groups, reported rates of hepatitis B increased steadily in China between 1990 and 2008, probably because of a failure to distinguish acute from chronic infections. Elements that prevented a clearer separation between acute and chronic cases included (1) missed opportunity to report cases accurately among clinicians, (2) low availability and use of tests to detect IgM against the hepatitis B core antigen (IgM anti-HBc) and (3) lack of systems to sort, manage and analyze surveillance data. CONCLUSIONS: To improve hepatitis B surveillance, China may consider (1) training clinicians to diagnose acute cases and to use IgM anti-HBc to confirm them, (2) improving access and use of validated IgM anti-HBc tests and (3) developing data management and analysis techniques that sort out acute from chronic cases.
  Vaccine 06/2013;
• Article: Seroprevalence of measles, mumps and rubella among children in American Samoa, 2011, and progress towards West Pacific Region goals of elimination.

  Abdirahman Mahamud, Yolanda Masunu-Faleafaga, Laura Walls, Nobia Williams, Philip Garcia, Eyasu Teshale, Roxanne Williams, Theresa Dulski, William J Bellini, Preeta K Kutty
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  ABSTRACT: INTRODUCTION: In line with the global goals for measles elimination, countries in the West Pacific Region (WPR) have set a goal to eliminate measles by 2012. Due to its contagiousness, high population immunity is needed for achieving and documenting measles elimination. We assessed population immunity to measles, mumps and rubella among first grade children in American Samoa (AS) through a seroprevalance study. METHODS: Using commercial indirect enzyme-linked immunosorbant IgG assays (Wampole Laboratories, Cranbury, NJ) we determined IgG antibodies against the measles, mumps, and rubella (MMR) viruses in sera collected from first grade students in AS in April-May 2011. Vaccination status was retrieved from the immunization cards. Factors associated with seropositivity of measles, mumps, and rubella were analyzed separately. RESULT: Among 509 first grade students, measles, mumps, and rubella seroprevalence were 92%, 90%, and 93%, respectively. The proportions of first grade students with documented one or two doses of MMR vaccine were 93% and 84%, respectively. The vaccination status of 6% of the first graders was unknown and 1% was unvaccinated. Receiving two-doses of MMR vaccines was associated with high measles and mumps seropositivity (p<0.01). CONCLUSION: The high measles seroprevalence among children shows the progress by American Samoa towards measles elimination. Achieving and maintaining high two-dose MMR vaccine coverage in all age groups will aid in attaining the measles elimination status and prevent transmission of measles from potential imported measles cases from other countries.
  Vaccine 06/2013;
• Article: A pilot randomized study to assess immunogenicity, reactogenicity, safety and tolerability of two human papillomavirus vaccines administered intramuscularly and intradermally to females aged 18-26 years.

  E Anthony S Nelson, Hugh Simon Lam, Kai C Choi, Wendy C S Ho, L W Eva Fung, Frankie W T Cheng, Rita Y T Sung, Michael Royals, Paul K S Chan
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  ABSTRACT: Intradermal administration of human papilloma virus (HPV) vaccines could be dose-sparing and cost-saving. This pilot randomized study assessed Cervarix(®) and Gardasil(®) administered either intramuscularly or intradermally, in different doses (full-dose or reduced to 20%) by different methods (needle and syringe or PharmaJet needle-free jet injection device). Following an initial reactogenicity study of 10 male subjects, sexually naïve women aged 18-26 years were randomized to the eight study groups to receive vaccine at 0, 2 and 6 months. 42 female subjects were enrolled and complete data were available for 40 subjects. Intradermal administration of either vaccine raised no safety concerns but was more reactogenic than intramuscular administration, although still tolerable. All subjects demonstrated a seroconversion (titre≥1:320) by Day 95. Further evaluation of intradermal HPV vaccination and its potential for cost reduction in resource poor settings is warranted.
  Vaccine 06/2013;
• Article: Intradermal fractional booster dose of inactivated poliomyelitis vaccine with a jet injector in healthy adults.

  Darius Soonawala, Pauline Verdijk, Alienke J Wijmenga-Monsuur, Claire J Boog, Patrick Koedam, Leo G Visser, Nynke Y Rots
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  ABSTRACT: For global eradication of poliomyelitis, inactivated poliovirus vaccine (IPV) needs to become available in all countries. Using fractional-doses (reduced-doses) may impact affordability and optimize the utilization of the production capacity. Intradermal administration has the potential to lower the dose without reducing immunogenicity. A needle-free jet injector may be a reliable way to administer vaccines intradermally. The primary objective of this randomized controlled trial was to compare the immunogenicity and tolerability of fractional-dose intradermal IPV (Netherlands Vaccine Institute, NVI) booster vaccination administered with a jet injector (PharmaJet) to full-dose and fractional-dose intramuscular vaccination with a needle and syringe. Immunogenicity was assessed by comparing the differences in the post-vaccination log2 geometric mean concentrations of neutralizing antibodies (GMC) between the study groups. A total of 125 Dutch adult volunteers with a well-documented vaccination history were randomized to one of four groups: full-dose intramuscular needle (IM-NS-0.5), full-dose intramuscular jet injector (IM-JI-0.5), 1/5th dose intramuscular needle (IM-NS-0.1), 1/5th dose intradermal jet injector (ID-JI-0.1). Vaccination with the JI was less painful (87% no pain) than vaccination with a NS (60% no pain), but caused more transient erythema (JI 85%, NS 24%) and swelling (JI 50%, NS 5%). Intradermal vaccination caused less vaccination site soreness (ID 16%, IM 52%). At baseline all subjects had seroprotective antibody concentrations. After 28 days, GMC were slightly lower in the ID-JI-0.1 group than in the reference group (IM-NS-0.5). The differences were not statistically significant, but the stringent non-inferiority criterion (i.e. a difference of 1 serum dilution in the microneutralization assay) was not met. After one year, differences in GMC were no longer apparent. In contrast, intramuscular vaccination with a fractional dose administered with a needle (IM-NS-0.1) was statistically inferior to full-dose intramuscular vaccination. This shows that intradermal but not intramuscular delivery of fractional-dose IPV may be sufficient for routine polio vaccination.
  Vaccine 06/2013;
• Article: Attenuated Salmonella enterica serovar Typhimurium lacking the ZnuABC transporter: An efficacious orally-administered mucosal vaccine against salmonellosis in pigs.

  Matteo Gradassi, Michele Pesciaroli, Nicola Martinelli, Jessica Ruggeri, Paola Petrucci, Walid Hamdy Hassan, Manuela Raffatellu, Frine Eleonora Scaglione, Serena Ammendola, Andrea Battistoni, Giovanni L Alborali, Paolo Pasquali
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  ABSTRACT: We have recently demonstrated that an attenuated strain of Salmonella enterica serovar Typhimurium unable to synthesize the zinc transporter ZnuABC (S. Typhimurium ΔznuABC), is able to protect mice against systemic and enteric salmonellosis and is safe in pigs. Here, we have tested the protective effects of S. Typhimurium ΔznuABC in pigs. Resistance to challenge with the fully virulent strain S. Typhimurium ATCC 14028 was assessed in animals vaccinated with S. Typhimurium ΔznuABC (two dosages tested), in controls vaccinated with a formalin-inactivated virulent strain and in unvaccinated controls. Clinical signs of salmonellosis, faecal shedding and bacterial colonization of organs were used to assess vaccine-induced protection. After the challenge, pigs vaccinated with the attenuated S. Typhimurium ΔznuABC strain did not display clinical signs of salmonellosis (fever or diarrhoea). The vaccine also reduced intestinal tract colonization and faecal shedding of the fully virulent Salmonella strain, as compared to control groups. S. Typhimurium ΔznuABC represents a promising candidate vaccine against salmonellosis in pigs.
  Vaccine 06/2013;
• Article: Systematic review of economic evaluation analyses of available vaccines in Spain from 1990 to 2012.

  Isabel Cortés, Santiago-Pérez Camarero, Juan Del Llano, Luz María Peña, Alvaro Hidalgo-Vega
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  ABSTRACT: OBJECTIVE: The objective of this survey was to describe the evolution of economic evaluation studies on vaccines available in Spain. METHODS: We conducted a systematic review of the economic evaluations published by Spanish researchers in major bibliographic databases available online from 1990 to 2012. For all references identified, we limited them to full economic evaluation carried out in Spanish vaccine programs. The following variables were analyzed: type of study, year of publication, vaccine evaluated, the herd immunity and the main methodological aspects proposed by international guidelines. The type of vaccines studied were Hepatitis A and B, Rotavirus, Influenza, Varicella, Tetanus, Measles, Human papillomavirus, Streptococcus pneumoniae infection and Neisseria meningitides serogroup C infection. RESULTS: A total of 34 references was included in the study. The number of economic evaluations has been increasing over the years by 86%. For many of the vaccines there were no economic evaluations, while others such as the vaccine against S. pneumoniae infection took up most of the studies. The non-vaccinated comparison was the most used strategy. The cost-effectiveness model was selected in 60% of cases. The most common health outcome was "cost per case prevented" and in 82% of the studies did not consider herd immunity. The results showed a cost-effectiveness ratio which was below breakeven. CONCLUSIONS: It is clear that the existence of a huge gap in this kind of work compared to other countries. Although the quality of the work discussed here was significant, we found many areas which could be improved. The reviewed literature exposed the great benefit of vaccination for society by analysing the health outcomes achieved for decades since its implementation. However, the evidence on the efficiency and effectiveness vaccination is not very high, and there are few studies about economic evaluation.
  Vaccine 06/2013;
• Article: The legal foundation of the production and use of herd-specific vaccines in Europe.

  Y Attia, I Schmerold, A Hönel
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  ABSTRACT: In veterinary medicine, herd-specific vaccines are primarily used in farm animals if traditional vaccines are either unavailable or do not perform as expected. As autogenous products, these vaccines are exempt from Directive 2001/82/EC, and therefore the production and use of herd-specific vaccines are regulated differently in each member state of the European Union (EU). This study is an overview of the diverse legal statuses of herd-specific vaccines among European countries. The study was conducted by analyzing legal documents, tailored questionnaires answered by subject-related authorities from sixteen European countries, and related literature. These analyses revealed that tremendous heterogeneity exists with respect to the legal requirements for the production and use of herd-specific vaccines among the countries that were examined. In particular, certain countries have detailed and precise regulations for these vaccines, whereas the legislation regarding these vaccines is vague or even nonexistent in other nations. The implementation of standardized definitions, guidelines for vaccine use in the field, and regulations for vaccine production are essential prerequisites for achieving legal consistency across Europe. These measures would also help countries enact pertinent national legislation with less divergence regarding the production and use of herd-specific vaccines and ensure the existence of comparable safety and quality standards for these vaccines among European countries.
  Vaccine 06/2013;
• Article: Control of humoral immunity and auto-immunity by the CXCR4/CXCL12 axis in lupus patients following influenza vaccine.

  Odile Launay, Stéphane Paul, Amélie Servettaz, Gwénaëlle Roguet, Flore Rozenberg, Frédéric Lucht, Claude Lambert, Emilie Presles, Claire Goulvestre, Jean-François Meritet, Florence Galtier, Claude Dubray, Pierre Lebon, Bernard Weill, Frédéric Batteux
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  ABSTRACT: BACKGROUND: CXCR4 is a chemokine receptor with multiple effects on the immune system, upregulated in patients with SLE, and correlated with disease severity. OBJECTIVE: This study has investigated whether the levels of CXCR4 expressed on leucocyte subsets in lupus patients are correlated with the efficacy and the safety of the influenza vaccine. METHODS: Twenty-seven patients were vaccinated and vaccine immunogenicity and tolerance were evaluated. CXCR4 was assayed on leucocyte subsets and correlated with clinical and immunological signs of diseases activity. RESULTS: A significant increase in the titres of antibodies to the three viral strains was observed along with trends towards an increased vaccine efficacy in patients with quiescent disease vs patients with active disease. Recent flu vaccine history and, to a lesser extent, immunosuppressive treatment may influence vaccine immunogenicity. Influenza immunization was not associated with clinical side-effects or clinical lupus flare but with an increase in rheumatoid factor levels. Our study also confirms the correlation of CXCR4 expression with biological autoimmunity as shown by the correlation between the percentage of CXCR4-positive T cells and the ANA titres at D0, and the reverse correlation between CXCR4 expression and vaccine immunogenicity as demonstrated by the higher percentage of CXCR4-positive T cells at D0 and D30 in non-responders vs responders. CONCLUSION: Altogether, our study confirms the efficacy and the safety of flu vaccine in SLE patients, highlights the role of CXCR4 as a surrogate marker for autoimmunity in lupus and shows that CXCR4 expression on T cells is predictive of vaccine efficacy in SLE patients.
  Vaccine 06/2013;
• Article: Live attenuated tularemia vaccines: Recent developments and future goals.

  Mark E Marohn, Eileen M Barry
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  ABSTRACT: In the aftermath of the 2001 anthrax attacks in the U.S., numerous efforts were made to increase the level of preparedness against a biological attack both in the US and worldwide. As a result, there has been an increase in research interest in the development of vaccines and other countermeasures against a number of agents with the potential to be used as biological weapons. One such agent, Francisella tularensis, has been the subject of a surge in the level of research being performed, leading to a substantial increase in knowledge of the pathogenic mechanisms of the organism and the induced immune responses. This information has facilitated the development of multiple new Francisella vaccine candidates. Herein we review the latest live attenuated F. tularensis vaccine efforts. Historically, live attenuated vaccines have demonstrated the greatest degree of success in protection against tularemia and the greatest promise in recent efforts to develop of a fully protective vaccine. This review summarizes recent live attenuated Francisella vaccine candidates and the lessons learned from those studies, with the goal of collating known characteristics associated with successful attenuation, immunogenicity, and protection.
  Vaccine 06/2013;
• Article: Quantitation of serogroups in multivalent polysaccharide-based meningococcal vaccines: Optimisation of hydrolysis conditions and chromatographic methods.

  Matthew C Cook, Alex Bliu, Jeremy P Kunkel
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  ABSTRACT: Quantitative determination of the individual polysaccharide components in multivalent meningococcal vaccines is an important step in manufacturing and regulatory control. Current methods are complicated due to the use of multiple chromatographic setups and/or other analytical techniques for the four meningococcal serogroup polysaccharides (A, C, Y, W135). In addition, different methods are sometimes used depending on whether or not the polysaccharide is conjugated to a carrier protein. In an effort to simplify such analyses, hydrolysis conditions were determined for the optimal yield of each characteristic saccharide from the respective repeating units. One condition was identified for mannosamine-6-phosphate from MenA, one for neuraminic acid from MenC, and one for both glucose and galactose from MenY and MenW135, respectively. These conditions, initially assessed for monovalent solutions, were then confirmed for a quadrivalent solution. The monosaccharide products were separated, identified and quantitated using a single HPAEC-PAD protocol, with a customised multi-stage linear gradient eluent profile and one column setup, for determination of all four serogroup components. Comparison to calibration curves constructed from sets of monosaccharide or hydrolysed polysaccharide standards allowed for the quantitation of each characteristic serogroup monosaccharide in polysaccharide and polysaccharide-conjugate vaccines. When required, molecular size separation using a non-cellulosic centrifugal filter device effectively removed all interfering saccharide excipient without loss of serogroup polysaccharides. These methods were used to analyse multiple lots of a number of different monovalent or multivalent real polysaccharide-based vaccine products, in liquid or lyophilised powder formulations, with or without excipients. The methods were demonstrated to be highly reproducible and very useful for the evaluation of antigen content and lot-to-lot consistency of manufacture. The methods described here represent an increase in precision, level of accuracy and efficiency compared to current methods, and may be adaptable for evaluation of other types of polysaccharide-based vaccines.
  Vaccine 06/2013;
• Article: Outer membrane protein A (OmpA) from Shigella flexneri 2a: A promising subunit vaccine candidate.

  Debasis Pore, Manoj K Chakrabarti
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  ABSTRACT: Shigellosis is the leading cause of childhood mortality and morbidity. Despite many years of extensive research a practical vaccine is not yet available against the disease. Recent studies illustrate that bacterial outer membrane proteins are budding target as vaccine antigen. Outer membrane proteins A (OmpA) are among the most immunodominant antigens in the outer membrane of gram negative bacteria and possess many characteristics desired of a vaccine candidate. We observe that OmpA of Shigella flexneri 2a is crossreactive and common antigen among Shigella spp. and the epitope is widely exposed on the cell surface as well as capable of evoking protective immunity in mice. The protective immunity involves participation of both the humoral and cellular immune responses, since OmpA boosts rapid induction of IgG and IgA in both the systemic and mucosal compartments and also activates Th1 cells. The immunopotentiating activity of OmpA is mediated by its ability to bind and stimulate macrophages and up-regulate the surface expression of MHCII, CD80 and CD40, leading to activation of CD4(+) T cells to secrete cytokines and express chemokine receptor and IL-12Rβ2, thereby orchestrating the bridge between innate and adaptive immune responses. This ability is dependent on Toll-like receptor 2 (TLR2), as demonstrated by lack of response by TLR2 knockdown macrophages to OmpA. Hence this property of OmpA to link innate and adaptive immunity via TLR2 offers a novel vista to develop vaccine against shigellosis.
  Vaccine 06/2013;
• Article: Estimating vaccination coverage against tick-borne encephalitis: Comment on: Košnik IG, Lah AK. A campaign to increase the vaccination rate in a highly endemic tick-borne encephalitis region of Slovenia. Vaccine 2013;31(5):732-4.

  Marta Grgič-Vitek
  Vaccine 06/2013;
• Article: Regulation of poxvirus vectored vaccines.

  James S Robertson
  Vaccine 06/2013;
• Article: Serotype distribution of Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease in Brazil before and after ten-pneumococcal conjugate vaccine implementation.

  Silvia R Dos Santos, Lilian F Passadore, Elizabeth H Takagi, Cristiane M Fujii, Cristina R M Yoshioka, Alfredo E Gilio, Marina B Martinez
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  ABSTRACT: The ten-pneumococcal conjugate vaccine (PCV10) was introduced into the national immunization program for childhood vaccination schedules by the Brazilian Health Public Service in March 2010. The aim of this study was to compare Streptococcus pneumoniae serotype distribution, antibiotic resistance patterns, and potential coverage before (January 2006-June 2010) and after (July 2010-September 2012) PCV10 introduction. The incidence of invasive pneumococcal disease (IPD), patient demographics, and disease characteristics were recorded. This study was conducted at the University Hospital of Sao Paulo University in Brazil from January 2006 to September 2012. Serotyping was performed using multiplex PCR typing, and antimicrobial sensitivity by Clinical and Laboratory Standards Institute (CLSI). A total of 259 S. pneumoniae strains were isolated from patients with IPD. The ages of the patients ranged from 3 months to 95 years old. The strains were isolated from cerebrospinal fluid, pleural fluid, and blood. The incidence of IPD among patients at HU-USP changed after the introduction of PCV10. The overall incidence of IPD was 3.42 cases per 1000 admissions in the vaccine pre- implementation period and of 2.99 cases per 1000 admissions in the vaccine post-implementation period. The incidence of IPD among children<2 y.o. attended at HU-USP changed significantly after the introduction of PCV10, from 20.30 to 3.97 of incidence. The incidence of PCV10- serotypes decrease from 16.47 to 0.44 in the same age, before and after PC10 implementation, respectively. Moreover, it was possible to realize the sensitivity to penicillin among isolates increased significantly in the post-vaccine period. Data from this study suggest that PCV10 contributed to decrease with PID rate among children less than 2 y.o. The resistance rate among pneumococcal isolates also could be observed since serotypes with greater resistance to beta lactam antibiotics were not easily isolated after vaccination.
  Vaccine 06/2013;
• Article: The marginal willingness-to-pay for attributes of a hypothetical HIV vaccine.

  Michael P Cameron, Peter A Newman, Surachet Roungprakhon, Riccardo Scarpa
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  ABSTRACT: This paper estimates the marginal willingness-to-pay for attributes of a hypothetical HIV vaccine using discrete choice modeling. We use primary data from 326 respondents from Bangkok and Chiang Mai, Thailand, in 2008-2009, selected using purposive, venue-based sampling across two strata. Participants completed a structured questionnaire and full rank discrete choice modeling task administered using computer-assisted personal interviewing. The choice experiment was used to rank eight hypothetical HIV vaccine scenarios, with each scenario comprising seven attributes (including cost) each of which had two levels. The data were analyzed in two alternative specifications: (1) best-worst; and (2) full-rank, using logit likelihood functions estimated with custom routines in Gauss matrix programming language. In the full-rank specification, all vaccine attributes are significant predictors of probability of vaccine choice. The biomedical attributes of the hypothetical HIV vaccine (efficacy, absence of VISP, absence of side effects, and duration of effect) are the most important attributes for HIV vaccine choice. On average respondents are more than twice as likely to accept a vaccine with 99% efficacy, than a vaccine with 50% efficacy. This translates to a willingness to pay US$383 more for a high efficacy vaccine compared with the low efficacy vaccine. Knowledge of the relative importance of determinants of HIV vaccine acceptability is important to ensure the success of future vaccination programs. Future acceptability studies of hypothetical HIV vaccines should use more finely grained biomedical attributes, and could also improve the external validity of results by including more levels of the cost attribute.
  Vaccine 06/2013;
• Article: Influenza vaccine: Development of a novel intranasal and subcutaneous recombinant adjuvant.

  R Segura-Velázquez, J Cervantes, E Acosta, I Sánchez-Betancourt, N Villalobos, L F Rodarte, M Restelli, G Fragoso, E Sciutto
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  ABSTRACT: The synthetic peptide GK-1, derived from Taenia crassiceps, enhances the protection induced by human influenza vaccine in both young and aged mice. Herein, the adjuvant properties of GK-1 fused to the pVIII protein of a heat-inactivated phagemid vector (FGK1) when co-administered with the influenza vaccine were assessed, to evaluate its feasibility as a low-cost adjuvant. In mice, FGK1 significantly increased the expected IgG and IgA anti-influenza antibody levels both in sera and in bronchoalveolar fluids when intranasally or subcutaneously co-administered with influenza vaccine. Single-dose pig co-immunization with FGK1 and influenza vaccine induced serum levels of IgG anti-influenza antibodies similar to those elicited by a two-dose immunization with the influenza vaccine alone. Preclinical evaluation of FGK1 with the influenza vaccine is currently in progress, in order to recommend its use for veterinary purposes.
  Vaccine 06/2013;
• Article: Transplacental transmission of BTV-8 in sheep: BTV viraemia, antibody responses and vaccine efficacy in lambs infected in utero.

  M T W van der Sluijs, D P H Schroer-Joosten, A Fid-Fourkour, M Smit, M P Vrijenhoek, V Moulin, A J de Smit, R J M Moormann
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  ABSTRACT: Bluetongue virus (BTV) is an insect vector transmitted virus which causes an economically important disease in ruminants. BTV infection during pregnancy can result in infection of the foetus, which may lead to the birth of persistently infected or immunotolerant offspring. Since persistently infected animals continuously produce large amounts of virus they could be a source of infection for the insect vector. This could significantly influence the epidemiology of the virus and hence might require additional measures to control a BTV outbreak. Therefore, we investigated the potential of BTV-8 to induce persistent infection or immunotolerance in lambs in an experimental setting. Infection of eighteen 70-75 days pregnant ewes with wild type BTV-8 led to the birth of 25 out of 44 BTV RNA positive lambs (foetal infected, FI). All 23 FI lambs born alive also had anti BTV antibodies at birth; infectious virus could be recovered from 5 out of 25 FI lambs. Viral RNA loads decreased rapidly after birth; 19 out of 20 FI lambs that remained in the experiment until week 14 after birth, were RNA negative at that time. Since persistence of BTV-8 infection could not be demonstrated, we investigated whether foetal infection had an effect on protection against a field virus infection and on efficacy of vaccination. To this end, 5 FI lambs and 5 foetal non-infected (FNI) lambs were vaccinated with the inactivated Bovilis(®) BTV-8 vaccine, five months after birth. Three weeks after the vaccination, all lambs were infected with wild type BTV-8. The foetal infection did not interfere with vaccination efficacy. In contrast, foetal BTV-8 infection induced an immune response which afforded protection against BTV challenge comparable to the level of protection induced by vaccination.
  Vaccine 06/2013;
• Article: Utilizing poxviral vectored vaccines for antibody induction-Progress and prospects.

  Simon J Draper, Matthew G Cottingham, Sarah C Gilbert
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  ABSTRACT: Over the last decade, poxviral vectors emerged as a mainstay approach for the induction of T cell-mediated immunity by vaccination, and their suitability for human use has led to widespread clinical testing of candidate vectors against infectious intracellular pathogens and cancer. In contrast, poxviruses have been widely perceived in the vaccine field as a poor choice of vector for the induction of humoral immunity. However, a growing body of data, from both animal models and recent clinical trials, now suggests that these vectors can be successfully utilized to prime and boost B cells and effective antibody responses. Significant progress has been made in the context of heterologous prime-boost immunization regimes, whereby poxviruses are able to boost responses primed by other vectors, leading to the induction of high-titre antigen-specific antibody responses. In other cases, poxviral vectors have been shown to stimulate humoral immunity against both themselves and encoded transgenes, in particular viral surface proteins such as influenza haemagglutinin. In the veterinary field, recombinant poxviral vectors have made a significant impact with numerous vectors licensed for use against a variety of animal viruses. On-going studies continue to explore the potential of poxviral vectors to modulate qualitative aspects of the humoral response, as well as their amenability to adjuvantation seeking to improve quantitative antibody immunogenicity. Nevertheless, the underlying mechanisms of B cell induction by recombinant poxviruses remain poorly defined, and further work is necessary to help guide the rational optimization of future poxviral vaccine candidates aiming to induce antibodies.
  Vaccine 06/2013;
• Article: An electrochemiluminescence assay for analysis of rabies virus glycoprotein content in rabies vaccines.

  Todd G Smith, James A Ellison, Xiaoyue Ma, Natalia Kuzmina, William Carson, Charles E Rupprecht
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  ABSTRACT: Vaccine potency testing is necessary to evaluate the immunogenicity of inactivated rabies virus (RABV) vaccine preparations before human or veterinary application. Currently, the NIH test is recommended by the WHO expert committee to evaluate RABV vaccine potency. However, numerous disadvantages are inherent concerning cost, number of animals and biosafety requirements. As such, several in vitro methods have been proposed for the evaluation of vaccines based on RABV glycoprotein (G) quality and quantity, which is expected to correlate with vaccine potency. In this study an antigen-capture electrochemiluminescent (ECL) assay was developed utilizing anti-RABV G monoclonal antibodies (MAb) to quantify RABV G. One MAb 2-21-14 was specific for a conformational epitope so that only immunogenic, natively folded G was captured in the assay. A second MAb (62-80-6) that binds a linear epitope or MAb 2-21-14 was used for detection of RABV G. Vaccine efficacy was also assessed in vivo using pre-exposure vaccination of mice. Purified native RABV G induced a RABV neutralizing antibody (rVNA) response with a geometric mean titer of 4.2IU/ml and protected 100% of immunized mice against RABV challenge, while an experimental vaccine with a lower quality and quantity of G induced a rVNA titer<0.05IU/ml and protected <50% of immunized mice. These preliminary results support the hypothesis that in vivo immunogenicity may be predicted from the in vitro measurement of RABV G using an ECL assay. Based upon these results, the ECL assay may have utility in replacement of the NIH test.
  Vaccine 06/2013;