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This article presented the World Health Organization’s (WHO) recommendations on the use of Rabies vaccines excerpted from the Rabies vaccines: WHO position paper – April 2018 published in the Weekly Epidemiological Record [1] This position paper replaces the 2010 WHO position paper on rabies vaccines [2] . It presents new evidence in the field of rabies and the use of rabies vaccines, focussing on programmatic feasibility, simplification of vaccination schedules and improved cost-effectiveness. The recommendations concern the 2 main immunization strategies, namely vaccination for post-exposure prophylaxis and vaccination for pre-exposure prophylaxis. In the context of post-exposure prophylaxis, recommendations are also provided on the use of rabies immunoglobulins. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation tables. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO’s current position on the use of vaccines in the global context. Recommendations on the use of cholera vaccines were discussed by the Strategic Advisory Group of Experts (SAGE) in October 2017; evidence presented at these meetings can be accessed at: http://www.who.int/immunization/sage/meetings/2017/october/presentations_background_docs/en/ . [ABSTRACT FROM AUTHOR]

• Heterologous mRNA boost following GLS-5310 DNA vaccination was well tolerated. • Neutralizing antibody responses were enhanced 110 fold to GMT of 1244.8. • Binding antibody responses were enhanced 1,187-fold to GMT of 405,920. • Boosted antibody responses similar to other vaccine combinations. • Boosted T cell responses were many-fold higher than other vaccine combinations. Heterologous boost regimens are being increasingly considered against SARS-CoV-2. We report results for the 32 of 45 participants in the Phase 1 CoV2-001 clinical trial (Kim et al., Int J Iinfect Dis 2023, 128:112–120) who elected to receive an EUA-approved SARS-CoV-2 mRNA vaccine 6 to 8 months following a two-dose primary vaccination with the GLS-5310 bi-cistronic DNA vaccine given intradermally and followed by application of suction using the GeneDerm device. Receipt of EUA-approved mRNA vaccines after GLS-5310 vaccination was well-tolerated, with no reported adverse events. Immune responses were enhanced such that binding antibody titers, neutralizing antibody titers, and T-cell responses increased 1,187-fold, 110-fold, and 2.9-fold, respectively. This paper is the first description of the immune responses following heterologous vaccination with a DNA primary series and mRNA boost. [ABSTRACT FROM AUTHOR]

Vaccines against bovine babesiosis must, ideally, induce a humoral immune response characterized by neutralizing antibodies against conserved epitopes and a cellular Th1 immune response. In Babesia bovis , proteins such as AMA-1, MSA-2c, and RAP-1 have been characterized and antibodies against these proteins have shown a neutralizing effect, demonstrating the implication of B and T-cell epitopes in the immune response. There is evidence of the existence of B and T-cell epitopes in these proteins, however, it remains to be defined, the presence of conserved peptides in strains from around the world containing B and T-cell epitopes, and their role in the generation of a long-lasting immunity. The aim in this paper was to identify peptides of Babesia bovis AMA-1, MSA-2c, and RAP-1 that elicit a neutralizing and long-lasting Th1 immune response. Peptides containing B-cell epitopes of AMA-1, MSA-2c and RAP-1, were identified. The immune response generated by each peptide was characterized in cattle. All peptides tested induced antibodies that recognized intraerythrocytic parasites, however, only 5 peptides generated neutralizing antibodies in vitro : P2AMA-1 (6.28%), P3MSA-2c (10.27%), P4MSA-2c (10.42%), P1RAP-1 (32.45%), and P4RAP-1 (36.98%). When these neutralizing antibodies were evaluated as a pool, the inhibition percentage of invasion increased to 52.37%. When the T cellular response was evaluated, two peptides: P3MSA2c and P2AMA1 induced a higher percentage (>70%) of activated CD4 +/CD45RO+ T cells than unstimulated cells. Additionally, both peptides induced the production of gamma interferon (IFN−) in PBMCs from vaccinated cattle after one year proving the implication of a long-lasting Th1 immune response. In conclusion, we identified conserved peptides containing B and T-cell epitopes in antigens of B. bovis that elicit a Th1 immune response and showed evidence that peptides from the same protein elicit different immune responses, which has implication for vaccine development in bovine babesiosis. [ABSTRACT FROM AUTHOR]

• RSV neutralization assays are complex biological assays used for measurement of functional antibody responses. • A broad variety of RSV neutralization assay formats are currently in use. • Use of the 1st International Standard for Antiserum to RSV is necessary to harmonize neutralization assay output across formats. • This paper outlines good practices for key assay components and data analysis to promote the quality and consistency of RSV neutralization assay results. Respiratory syncytial virus (RSV) is a leading cause of respiratory illness among children and infants worldwide, yet no licensed vaccine exists to reduce the risk of disease. At least 16 RSV vaccine candidates are currently in clinical development and many are designed to induce robust virus neutralizing immune responses. RSV neutralizing antibody (nAb)-mediated interventions such as intravenous immunoglobulin (IVIG) and palivizumab provide passive protection against serious lower respiratory tract disease due to RSV, validating nAbs as a correlate of protection. To identify correlates of protection for vaccine candidates that have demonstrated their protective efficacy, an investigator can use assays designed to measure nAb responses. However, there is no standard method of measurement; individual laboratories have developed their own methods to measure the ability of nAbs to reduce the infectivity of a defined virus dose in a variety of cell lines, leading to establishment of the broad variety of RSV neutralization assay formats currently in use. Standardizing the RSV neutralization assay is an essential step toward better assessment of nAb responses to vaccine candidates. Use of a common reference standard by all makes comparing the immunogenicity of different vaccine candidates feasible. In the context of vaccine development, the WHO 1st International Standard for Antiserum to RSV (RSV IS) has been shown to be suitable for harmonizing results across laboratories and assay formats used to measure nAb titers to RSV/A and RSV/B in human sera. This review describes the broad variety of RSV virus neutralization assay formats currently in use and the importance of the RSV IS for harmonization of results across formats and across laboratories. It also outlines good practices for key assay components and data analysis to promote the quality and consistency of measuring RSV nAb titers in serum specimens. [ABSTRACT FROM AUTHOR]

Different schedules for pediatric use of the 13-valent pneumococcal conjugate vaccine (PCV-13) are recommended in different countries and the U.S. Advisory Committee on Immunization Practices (ACIP) has considered potential of changing from 3 primary doses plus a booster (3p + 1) to two primary doses plus a booster (2p + 1) for protection against Streptococcus pneumoniae. In this paper, we report results of IgG antibody measured by ELISA and opsonophagocytic assay (OPA) after 2p, 3p, at child age 15 months of pre-booster and 18 months (post-booster) in serum samples opportunistically available from a prior study that focused on PCV effectiveness against AOM. A total of ~ 100 sera for each of the 4 study time points (390 sera tested) from 169 children were tested. Geometric mean concentrations (GMCs) and percentage of children exceeding the presumed protective antibody thresholds measured by ELISA and OPA were calculated. 2p doses produced lower antibody levels measured by ELISA but not OPA until the booster dose for serotypes 6A, 6B, 5 and 23F only. Booster dosing at 15 months resulted in significant increases in antibody. There was no difference in the percentage of children with ≥ correlate of protection (COP) for OPA for 2p vs 3p doses except for serotype 23F. A 2p + 0 or 3p + 0 schedule would likely result in many children failing to sustain protective levels of antibody into the second year of life. We conclude that protection from invasive pneumococcal infection in early childhood would be similar for most serotypes in PCV13 using a 2p + 1 or 3p + 1 but not a 2p + 0 or 3p + 0 schedule. [ABSTRACT FROM AUTHOR]

Abstract: As women vaccinated against measles transfer low amounts of antibodies, an increasing number of infants lack early protection through maternal antibodies until being immunised themselves. This paper reviews the literature on disease burden of measles in the population too young to be immunized according to the respective national recommendations during recent outbreaks in EU and EEA/EFTA countries. In addition, specific control strategies adopted to protect this young population are reviewed. Pubmed, Unbound Medline, Web of Knowledge and the Eurosurveillance database were searched using MESH terms: measles and epidemiology, measles and infants, prevalence of measles, measles and outbreaks and measles and epidemic. Additionally, data from Euvac.net and ECDC were consulted. Databases were searched from January 2001 to September 2011. Fifty-three papers were included in the analysis. The percentage of all measles cases during outbreaks affecting young infants ranged from 0.25% to 83.0%. Specific control strategies were adopted: e.g. administration of the first or second vaccine dose earlier than recommended. Infants younger than 12 months are often involved in measles outbreaks, and advancing the first vaccine dose could reduce the burden of disease. However, immunization before 9 months of age is not systematically recommended because of dysmature humoral immune responses of infants. High coverage and timely administration of the recommended series of vaccines are the most important measures to decrease measles incidence and measles circulation and protect vulnerable infants from infection. [Copyright &y& Elsevier]

Determining a recommended dosage schedule is a crucial component of vaccine administration, and is often subject to reassessment. Ideally, recommendations will be supported by multiple arm clinical trials. However, the considerable cost in both resources and time means that a method of predicting post-vaccine humoral antibody levels associated with a hypothetical schedule using data collected from a currently implemented schedule would be of significant benefit to vaccination practice. In this paper we propose such a methodology, which permits statistical estimation of the population mean and standard deviation of log transformed antibody titers of various post-vaccination time points of a hypothetical schedule, using a longitudinal sample of antibody titers from an observed schedule. The method is based on the decomposition of humoral antibody kinetic history into distinct phases, for example, peak phase, decay phase and post-booster phase. The method is feasible because each phase has its own discernable kinetic laws. Of particular interest will be estimation of antibody levels immediately preceding a booster dose (typically the lowest level attained during the schedule), and the antibody levels following a booster dose. [ABSTRACT FROM AUTHOR]

Since inactivated influenza vaccines mainly confer protective immunity by inducing strain-specific antibodies to the viral hemagglutinin, these vaccines only afford protection against infection with antigenically matching influenza virus strains. Due to the continuous emergence of antigenic drift variants of seasonal influenza viruses and the inevitable future emergence of pandemic influenza viruses, there is considerable interest in the development of influenza vaccines that induce broader protective immunity. It has long been recognized that influenza virus-specific CD8 + T cells directed to epitopes located in the relatively conserved internal proteins can cross-react with various subtypes of influenza A virus. This implies that these CD8 + T cells, induced by prior influenza virus infections or vaccinations, could afford heterosubtypic immunity. Furthermore, influenza virus-specific CD4 + T cells have been shown to be important in protection from infection, either via direct cytotoxic effects or indirectly by providing help to B cells and CD8 + T cells. In the present paper, we review the induction of virus-specific T cell responses by influenza virus infection and the role of virus-specific CD4 + and CD8 + T cells in viral clearance and conferring protection from subsequent infections with homologous or heterologous influenza virus strains. Furthermore, we discuss vector-based vaccination strategies that aim at the induction of a cross-reactive virus-specific T cell response. [ABSTRACT FROM AUTHOR]

Abstract: Background: Seroprevalence studies provide important data on performance of immunization programs, susceptible groups and populations at-risk of future outbreaks. Identifying risk factors that affect seroconversion of the oral polio vaccine (OPV) will enable the polio eradication initiatives to increase seroprevalence. This paper describes the first population-based seroprevalence survey in Pakistan. Methods: This study evaluated the seroprevalence of poliovirus (PV) types 1, 2, and 3 antibodies to OPV in an illustrative sample of 554 subjects 6–11 months of age in three geographic locations of Pakistan (Lahore, Karachi, and Peshawar) representing a low socioeconomic at-risk populations. Antibody titers were measured and sero protection rates and geometric median titers were compared among different geographic regions and populations, as were demographics and OPV vaccination history collected by questionnaire. Univariate and multivariate analyses were conducted on subject characteristics to assess for potential risk factors for failure to sero-convert. Results: The average seroprevalence of PV1, PV2, and PV3 was 96.0%, 87.9% and 86.7%, respectively. The lowest sero protection rate for all three serotypes was for Karachi with 90.2%, 73.8%, and 78.8% for PV1, PV2, and PV3, respectively. Significant regional variation in PV3 seroprevalence was found (range: 74.2–100%). In the univariate analysis, age, total and campaign OPV doses were associated with higher seroprevalence, whereas stunting, respondent education and diarrhea in the past six months were significant risk factors for failure to sero-convert. Conclusions: These findings demonstrate consistently high levels of antibody response to PV1 and more geographically varied response to PV2 and PV3. Additionally, important risk factors affecting seropositivity were identified. [Copyright &y& Elsevier]

Abstract: Background: Pertussis is an acute infectious illness, caused by the bacteria Bordetella pertussis and commonly known as “whooping cough”. Waning immunity after vaccination or after natural infection contributes significantly to the increasing incidence rates in adolescents and adults. Prevention of pertussis in industrialized countries is mainly based on immunization with acellular vaccines in combination with other antigens. A booster dose with an adult-formulation tetanus-diphtheria toxoid and acellular pertussis vaccine (Tdap) is now recommended for all adolescents by several countries, and replacement of the decennial Td dose with a single or more doses of Tdap is recommended for adults. Objective: Our review aims at describing the current knowledge on the impact of acellular pertussis vaccination in adolescents and adults, with particular focus on specific risk groups: adolescents, pregnant women and their newborns, and health care workers (HCWs), and secondly at suggesting possible immunization strategies. Methods: Data were retrieved by searches of Pubmed, references, from relevant articles and open-access websites. Results: In countries where an adolescent booster dose was adopted, a certain decrease of incidence rates was observed. No serologic correlate of protection after immunization exists, but subjects with high antibody levels against pertussis antigens are less likely to develop the disease. Tdap vaccine was demonstrated to induce antibodies to pertussis antigens exceeding those associated with efficacy in infants, in both adolescents and adults. Tdap use in pregnant women seems to be safe and might represent a useful tool in order to prevent pertussis cases in the first months of life. Neonatal immunization with monovalent acellular pertussis vaccine can efficiently prime T and B cells and act as a basis for future immune responses. Cocooning strategies involving all those surrounding newborns have started to be implemented. Their impact on infant pertussis cases will be evaluated in the coming years. Coverage in HCWs should be increased, given their important role in pertussis transmission in health care settings. Conclusions: Despite the more recent position paper of WHO gives priority to infant and childhood vaccination against pertussis and leaves adolescent, adult and risk group immunization as an option for the future, data are quickly accumulating to support the need to consider pertussis vaccination as a crucial preventative intervention even in adolescents and special risk groups. [Copyright &y& Elsevier]

Abstract: Aim: We designed this study to investigate if immunoglobuline G-Pertussis toxin (IgG-PT) against Bordetella pertussis in umbilical cord blood can reliably be determined in dried blood spots on filter paper (Guthrie) cards. Patients and methods: We prospectively included 129 mothers and their newborns born in a general hospital in the Netherlands. The relation between IgG-PT against B. pertussis from the umbilical cord measured in dried blood spots (Guthrie card) and in serum samples was studied by means of a Bland–Altman graph, using regression analysis to evaluate the level of agreement of both measurement methods. Results: IgG-PT in Guthrie cards show a high coefficient of correlation with IgG-PT in serum samples from the umbilical cord when calibrated against blood spot calibrators (p <0.05). Conclusion: Maternal IgG-PT against B. pertussis measured in cord blood applied to Guthrie cards and calibrated against blood spot calibrators show good agreement with measurement of IgG-PT in cord serum. This offers new perspectives for future studies concerning B. pertussis antibodies. [Copyright &y& Elsevier]

Abstract: Japanese encephalitis is an infectious disease caused by the Japanese encephalitis virus, which is widespread throughout Asia. The worldwide incidence is 50,000 cases per year. There is no specific treatment available, but inactivated mouse brain-derived vaccine was used from the 1950s to prevent infection. However, quality control of mouse brain-derived vaccines is difficult, and therefore a new freeze-dried, cell culture-derived Japanese encephalitis vaccine (inactivated) (JEBIK V; development code: BK-VJE) was developed. In this paper, we report an analysis of neutralizing antibody titers in vaccinated subjects enrolled in clinical study of BK-VJE at various doses, and study of BK-VJE with the mouse brain-derived vaccine as a control. The results show that BK-VJE has superior immunogenicity compared to mouse brain-derived vaccine. [Copyright &y& Elsevier]

Abstract: Meningococcal disease is particularly severe. The case-fatality rate is 7.78% in Europe and 10–14% in the USA. This paper reports the results of a sero-epidemiological study in Italy on meningitis due to Meningococcus C before the introduction of the monovalent conjugate vaccine. In 2003–2004, a total of 577 sera were collected in 17 of the 20 Italian Regions. Serum Bactericidal Assay (SBA) was performed by using rabbit complement serum according to standardized SBA. The results showed that the percentages of protected subjects decreased from 6 to 12 months of age, increased from 1 to 4 years, decreased again until the age of 8 years and from 13 to 16 years, and were particularly high in 9- and 17-year-old subjects. The geometric mean titre of bactericidal antibodies (SBAbs GMT) was low in subjects under 1 year of age, significantly increased in 1–9-year-old children and decreased in adolescents and young adults. Finally, in each one-year age-group, low levels of antibodies were observed in subjects under 1 year of age, in 10-year-old subjects and in 14–16-year-old adolescents. High titres were observed in 3-, 8-, 9- and 17-year-old subjects. Our results therefore indicate that meningococcus C has the highest probability of spreading among 1–4, 8–10 and 14–17-year-old subjects in Italy. [Copyright &y& Elsevier]

Abstract: The outer membrane protein LP2086, a human factor H binding protein, is undergoing clinical trials as a vaccine against invasive serogroup B meningococcal (MnB) disease. As LP2086 is a surface protein, expression of capsular polysaccharide could potentially limit accessibility of anti-LP2086 antibodies to LP2086 expressed on the surface of bacteria. To determine whether variability in expression levels of the serogroup B capsule (Cap B) might interfere with accessibility of anti-LP2086 antibody binding to LP2086, we evaluated the ability of anti-Cap B and anti-LP2086 antibodies to bind to the surface of 1263 invasive clinical MnB strains by flow cytometry. One of the anti-LP2086 monoclonal antibodies used recognizes virtually all LP2086 sequence variants. Our results show no correlation between the amount of Cap B expressed and the binding of anti-LP2086 antibodies. Furthermore, the susceptibility of MnB bacteria to lysis by anti-LP2086 immune sera was independent of the level of Cap B expressed. The data presented in this paper demonstrates that Cap B does not interfere with the binding of antibodies to LP2086 expressed on the outer membrane of MnB clinical isolates. [Copyright &y& Elsevier]

Abstract: This study aimed to determine the immunogenicity of a 9-valent pneumococcal conjugate vaccine (PCV-9) in a subgroup of Gambian children enrolled in a large vaccine efficacy trial. To place the antibody results in context, in this paper we also report previously unpublished data on serotype-specific clinical vaccine efficacy from the main trial. In the sub-study, a single 2–4ml venous blood specimen was collected from 212 Gambian children 4–6 weeks after the administration of a third dose of PCV-9 or placebo. IgG antibodies to pneumococcal serotype 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F polysaccharides were measured by ELISA. The proportions of infants with antibody concentrations above 0.2, 0.35 and 1.0μg/ml, and the geometric mean concentrations (GMCs) of anti-pneumococcal polysaccharide antibodies were substantially higher for each serotype in children who received three doses of PCV-9 than those in the placebo group. Among PCV-9 recipients, GMCs ranged between 2.61 and 11.09μg/ml with the highest being against serotype 14 and the lowest against 9V polysaccharide. The estimated overall protective antibody level for all nine serotypes, based on the vaccine efficacy against vaccine-type invasive pneumococcal disease (IPD) of 77% (95% CI: 51, 90) observed in the trial, was 2.3μg/ml (95% CI: 1.0, 5.0). The PCV-9 studied was immunogenic in a Gambian population where it was also found to be efficacious. [Copyright &y& Elsevier]

Abstract: The need to enhance the immunogenicity of purified subunit antigens has prompted the development of new adjuvants. The adjuvant emulsion MF59™ has been tested in animals in combination with different antigens and finally evaluated in humans. It was licensed after the successful outcome of preclinical and clinical testing. This paper summarizes the main characteristics of the MF59™ adjuvant, including animal testing, clinical experience with various vaccines, and information from current postmarketing surveillance data. This review supports the hypothesis that MF59™ is a safe adjuvant for human use. [Copyright &y& Elsevier]

Summary: It has been hypothesised that lower vaccine uptake in childhood among some groups, such as children of lone parents or from larger families, may be due to their higher levels of residential mobility. This paper aimed to explore this association in a large cohort of children born in the UK at the turn of the century. Using multi-variable Poisson regression we found that children who lived in families which had moved during pregnancy or more frequently were more likely to be partially immunised with the primary immunisations and unimmunised against measles, mumps and rubella. Mobility was not associated with being unimmunised with the primary vaccines, or with single measles, mumps and rubella antigen vaccine use. These findings suggest that policies are needed to encourage the building and maintenance of relationships between health care professionals and parents, before and after they move, and better use of IT systems to aid follow-up of mobile families. [Copyright &y& Elsevier]

Summary: This paper presents 7- and 10-year follow-up immunogenicity data from two studies, which explored long-term persistence induced by combined tetravalent DTPw-HBV vaccines. The 10-year follow-up study compared two identical antigen-content, but different formulations of DTPw-HBV vaccine (adsorbed on either Al(OH)3 or Al(PO4), whilst the 7-year follow-up study compared two different formulations of DTPw-HBV vaccines containing 5 and 10μg of hepatitis B surface antigen (HBsAg), following a birth dose of HBV. Primary vaccination took place at 2, 4, 6 months and booster dosing at 18 months. A booster dose of local DTPw vaccine was given at 4 years of age to all returning subjects. At the end of the 7-year study, 90.9% subjects receiving 10μg HBsAg had anti-HBs antibody concentrations ≥10mIU/ml; the majority of subjects remained seroprotected against diphtheria and tetanus (≥90.9 and 100%, respectively) and 100% had seropositive levels for pertussis antigens. At the end of the 10-year follow-up study, ≥60.9% subjects had seroprotective concentrations of anti-HBs antibodies; ≥95.2 and 100% subjects were seroprotected against diphtheria and tetanus, respectively; ≥78.3% subjects were seropositive for pertussis. The results demonstrate long-term antibody persistence induced by combined DTPw-HBV vaccine. [Copyright &y& Elsevier]

Summary: Enzyme linked immunosorbent assay (ELISA) has been widely used to measure antibody titers for evaluating the immunogenicity of a vaccine. However, there is as yet no generally accepted way of expressing the ELISA results in the case of experimental vaccines, since there is usually no uniform standard. Both end point and single dilution methods have significant disadvantages. In this paper, we obtained reproducible data with fewer dilutions of samples by addition of serially diluted standard serum to each ELISA plate. Since this ELISA method gives reliable antibody titer with less labor than other methods, it can strongly support vaccine development. [Copyright &y& Elsevier]

Abstract: This paper reviews literature on passively transferred maternal antibodies against measles in infants. The amount and decay of these antibodies can be a result of changing patterns in society: increasing cohorts of women are vaccinated against measles instead of having naturally acquired immunity, the age of first childbirth is increasing and young adults are less exposed to natural boosters. The concentration and persistence of maternal antibodies differ in infants of women vaccinated against measles versus infants of naturally immune women. The date for commencing universal measles vaccination should take into account the presence of these antibodies since they can hamper the immunological response to vaccination. Each country should therefore consider adapting the timing of vaccination in relation to its measles sero-epidemiological situation. The possibility of priming the immune system with an early vaccine dose and boosting later on offers opportunities for vaccination at very young age. [Copyright &y& Elsevier]

Abstract: The envelope glycoprotein G of rabies virus induces the production of neutralising antibodies, which are important in protection against rabies. Therefore, titration of anti-envelope glycoprotein antibodies is a good indicator of the degree of immunity in people during anti-rabies treatment or after vaccination. According to the World Health Organization (WHO) guidelines, a booster vaccine dose should be given if the rabies antibody titre falls below 0.5IU/ml. Titration of anti-rabies antibodies is also useful for plasma centers in the preparation and standardization of human anti-rabies gamma-globulins for therapeutic use and to a lesser extent for the diagnosis of rabies in human sera and cerebrospinal fluid (CSF). This paper presents a new enzyme-linked immunosorbent assay (ELISA), PLATELIA™ RABIES II, developed for rabies envelope glycoprotein antibody detection or titration and its comparison to the current reference method (RFFIT). The data collected during validation of the test in a multicenter study are analysed to give a sound overall knowledge of the capabilities of the PLATELIA™ RABIES II, for instance specificity, linearity, accuracy, precision, detection limit and quantitation limit. To this aim, human serum samples from a total of 1348 vaccinated or non-vaccinated people were tested in parallel using the new ELISA and the RFFIT for the presence of anti-rabies antibodies. Data generated indicate a linear relationship across the range of titration between the two methods. The sensitivity reaches 98.6% and the specificity 99.4%. This study indicates that this new ELISA test is as sensitive and specific as the current standardized reference method. The method is simple, safe, rapid and can be considered as a useful alternative to the neutralisation test. [Copyright &y& Elsevier]

Abstract: The use of transgenic plants for the production of pharmaceutical compounds has received increasing attention in the last few years. However, many technological and regulatory issues regarding the practical exploitation of this alternative system of production remain to be solved; a situation that explains the lack of commercial products derived from such a system. This paper reports the expression in transgenic plants and cells of a single-chain antibody variable-region fragment (scFv) and a mouse monoclonal antibody to the hepatitis B virus surface antigen (HBsAg). The large-scale purification of the scFv from plants and its use for immunopurification of HBsAg are also described, together with elements concerning regulatory issues and technologies for compliance with good manufacturing and agricultural practices. [Copyright &y& Elsevier]

Abstract: Induction of CTL responses against protein antigens is an important aim in vaccine development. In this paper we present fusion-active virosomes as a vaccine delivery system capable of efficient induction of CTL responses in vivo. Virosomes are reconstituted viral membranes, which do not contain the genetic material of the virus they are derived from. Foreign macromolecules, including protein antigens, can be encapsulated in virosomes during the reconstitution process. Functionally reconstituted virosomes retain the cell binding and fusion characteristics of the native virus. Thus, upon uptake by cells through receptor-mediated endocytosis, virosomes will deliver their content to the cell cytosol. In a previous study, we demonstrated that protein antigens delivered in this manner to dendritic cells are efficiently processed for both MHC class I and class II presentation. Here, we studied in vivo induction of cellular immune responses against virosome-encapsulated ovalbumin (OVA) in mice. As little as 0.75μg OVA delivered by fusion-active virosomes was sufficient to induce a powerful class I MHC-restricted CTL response. All immunization routes that were used (i.m., i.p. and s.c.) resulted in efficient induction of CTL activity. The CTLs induced were cytotoxic in a standard 51Cr-release assay and produced IFNγ in response to OVA peptide. Thus, virosomes represent an ideal antigen delivery system for induction of cellular immunity against encapsulated protein antigens. [Copyright &y& Elsevier]

The use of foot-and-mouth disease (FMD) vaccines that do not induce antibodies against non-structural proteins (NSP) is extremely relevant for the demonstration of regions “free of FMDV infection” and control strategies. In this study cattle were primed and boosted with five doses of oil vaccines containing high antigenic payloads on days 0, 90, 130, 160 and 200. The serological response against NSP was measured using four commercially available assays: two 3ABC-ELISAs; one 3B-ELISA (and complementary 3A-ELISA) and an enzyme-immunotransfer blot assay (EITB). Additionally, locally produced NSP antibodies detection reagents and VIAA antibodies were evaluated. A high level of specific immune response against vaccine strains was shown. After four doses of vaccine, non-reactive animals were detected by any of the NSP assays. After the fifth immunization, 2 of 17 animals were reactive in one ELISA kit, but these samples proved negative by confirmatory tests. Antibodies against NSP were not detected in single dose immunized cattle. The principle of the NSP-ELISA used as a screening test for large sero-surveys in South America is established and this paper emphasizes the importance of using vaccines that have demonstrated no interference with NSP antibodies detection assays. [Copyright &y& Elsevier]

DNA vaccination induces potent cellular immune responses against infectious and parasitic intracellular pathogens. This paper illustrates that DNA immunisation protocols can be adapted to induce high titre antibody responses with potential to improve the treatment of systemic snake envenoming that kills 20,000 people annually in Africa. Envenoming by the saw-scaled vipers and puff adders are responsible for the majority of these deaths. DNA sequences encoding haemorrhagic, pro- and anti-coagulant and other haemostasis-disruptive venom toxins from these vipers showed extensive cross-specific and cross-generic sequence and structural similarities. The predicted antigenic profiles of these toxin sequences are utilised to design DNA immunisation constructs to generate toxin-specific antibodies with potential to polyspecifically neutralise venoms from the most medically-important African vipers. [Copyright &y& Elsevier]

The identification of new vaccine candidates for leptospirosis is of great interest. This paper describes the identification of two homologous immunogenic proteins, LigA-m and LigB-m, of Leptospira interrogans serovar manilae strain UP-MMC-NIID, which show strong similarity with LigA found recently in L. interrogans serovar pomona. Southern blot analysis indicated the conservation of the lig genes among pathogenic leptospires. LigA-m protein was shown to be a surface-exposed lipoprotein expressed during in vitro culture. Both LigA-m and LigB-m induced protective immunity against a challenge with a homologous serovar of L. interrogans in mice. Furthermore, patients’ sera infected with heterologous serovars’ strains contained antibodies against LigA-m and LigB-m. Our results suggest that LigA-m and LigB-m proteins are new vaccine candidates for the prevention of leptospirosis. [Copyright &y& Elsevier]

Abstract: Recombinant hepatitis B vaccine has been used widely in the world since 1991. The side effects of hepatitis B vaccine are seen rarely. In this paper, we present clinical and laboratory progress of an infant who gets severe thrombocytopenia after the second dosage hepatitis B vaccine. Our case is different from other cases because our patient is very young, the number of platelet is the lowest in the literature, and intravenous immunoglobulin (IVIG) are used in the treatment. Although it is a severe thrombocytopenia, the patient has recovered without any bleeding. [Copyright &y& Elsevier]