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Fowl adenoviruses (FAdVs) are promising vectors for poultry vaccines and gene therapy. The commonly used human cytomegalovirus (CMV) promoter in recombinant FAdV-9 viruses (recFAdV-9s) leads to foreign gene expression that elicits an antibody response. Despite its strength, studies have shown that the CMV promoter is prone to silencing by methylation hampering the in vivo application of vectors containing this promoter. Therefore, to improve our virus vector system and circumvent potential limitations of silencing, we engineered recFAdV-9s with foreign gene expression cassettes carrying the CMV enhancer/chicken β-actin (CAG) or the human elongation factor 1 alpha (EF1α) promoters with or without the posttranscriptional regulatory element of woodchuck hepatitis virus (WPRE). Chicken hepatoma cells (CH-SAH) infected with recFAdV-9s carrying either CAG or EF1α promoters expressed higher levels of foreign protein than those infected with recFAdV-9 carrying the CMV promoter. Incorporation of the WPRE element rendered lower gene expression regardless of promoter type. Surprisingly, most chickens inoculated with recFAdV-9 containing the CMV promoter had the highest antibody response to foreign protein compared to other promoters. Our findings suggest the importance of promoter selection for candidate virus vector vaccines based on humoral immune response rather than foreign protein expression levels in vitro., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The human leukocyte antigen (HLA) system plays critical roles in regulating immune responses to various vaccines. This study aimed to evaluate the association of HLA class II gene polymorphisms and the long-term duration of anti-HBs response in children vaccinated against hepatitis B during infancy., Methods: Totally 297 children 5-7years after the completion of primary vaccination against hepatitis B in infancy, without booster immunization or natural resolved infection, were enrolled. Of them, 86 children with anti-HBs <10mIU/ml were considered as long-term non- or hypo-responders, and 211 others with anti-HBs ≥10mIU/ml were defined as long-term responders. Ten alleles in HLA-DR and -DQ subregions were detected by polymerase chain reaction with sequence-specific primers., Results: The frequency of HLA-DQB1∗0401 was 15.1% in the long-term non- or hypo-responder group, relatively higher than 7.6% in the long-term responder group (OR=2.17, 95% CI 1.01-4.73), however, the difference had no statistical significance after Bonferroni correction (P=0.470). The frequencies of seven HLA-DRB1 alleles, including ∗01, ∗03, ∗04, ∗07, ∗08, ∗11, and ∗1301/1302, and two HLA-DQB1 alleles, including ∗0201 and ∗0501, were each similarly distributed in the long-term non- or hypo-responders and responders respectively., Conclusion: None of the ten HLA class II gene alleles previously reported to be related with short-term antibody response to hepatitis B vaccine is associated with the long-term antibody response after vaccination during infantile., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Although immune response to vaccines can be influenced by several parameters, human genetic variations are thought to strongly influence the variability in vaccine responsiveness. Systematic reviews and meta-analyses are needed to clarify the genetic contribution to this variability, which may affect the efficacy of existing vaccines. We performed a systematic literature search to identify all studies describing the associations of allelic variants or single nucleotide polymorphisms in immune response genes with vaccine responses until July 2013. The studies fulfilling inclusion criteria were meta-analyzed. Thirteen studies (11,686 subjects) evaluated the associations of human leukocyte antigen (HLA) and other immunity gene variations with the responses to single vaccines, including MMR-II (measles and rubella virus), HepB (hepatitis virus), influenza virus, and MenC (serogroup C meningococcus) vaccines. Seven HLA genetic variants were included in the meta-analyses. The pooled ORs showed that DRB1*07 (2.46 [95% CI=1.60-3.77]; P for heterogeneity=0.117; I(2)=49.1%), DQA1*02:01 (2.21 [95% CI=1.22-4.00]; P for heterogeneity=0.995; I(2)=0.0%), DQB1*02:01 (2.03 [95% CI=1.35-3.07]; P for heterogeneity=0.449; I(2)=0.0%), and DQB1*03:03 (3.31 [95% CI=1.12-9.78]; P for heterogeneity=0.188; I(2)=42.4%) were associated with a significant decrease of antibody responses to MMR-II, HepB, and influenza vaccines. The pooled ORs showed that DRB1*13 (0.52 [95% CI=0.32-0.84]; P for heterogeneity=0.001; I(2)=85.1%) and DRB1*13:01 (0.19 [95% CI=0.06-0.58]; P for heterogeneity=0.367; I(2)=0.0%) were associated with a significant increase of antibody responses to the above vaccines. While our findings reinforce the concept that individuals with a particular HLA allelic composition are more likely to respond efficiently to vaccines, future studies should be encouraged to further elucidate the link between genetic variation and variability of the human immune response to vaccines., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background and Aim: Evidence is accumulating that several markers in the human leukocyte antigen (HLA) region have been associated with decreased or increased antibody response to hepatitis B vaccine in different individuals. This meta-analysis is to assess the associations of HLA class II DRB1 and DQB1 alleles with immunologic response to hepatitis B vaccine in healthy people., Methods: A systematic review of cohort studies in healthy people was performed. We searched databases for relevant studies that were published in English or Chinese up to February 17, 2012. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of HLA alleles response to hepatitis B vaccine were pooled by using of a fixed-effects or random-effects model depending on absence or presence of significant heterogeneity. All statistical tests were two-sided., Results: Fifteen studies were included in this meta-analysis after scanning 774 potentially relevant articles. A total of 2308 subjects (including 1215 responders, 873 nonresponders and 220 control populations) were included. For DRB1 alleles, pooled ORs showed that three HLA variants, DRB1*01, DRB1*1301 and DRB1*15 were associated with a significant increase antibody response to hepatitis B vaccine, their pooled ORs were 2.73, 5.94 and 2.29 respectively. While DRB1 *03 (DRB1*0301), DRB1*04, DRB1*07 and DRB1*1302 were opposite, their pooled ORs were 0.55(0.42), 0.57, 0.24 and 0.25 respectively. And for DQB1 alleles, pooled ORs showed that DQB1*05 (DQB1*0501), DQB1*06, DQB1*0602 were associated with a significant increase antibody response to hepatitis B vaccine. Their merger ORs were 1.85, 2.35, 2.34 and 3.32 respectively. While DQB1*02 (pooled OR=0.27) was adverse. Sensitivity and specificity analysis of HLA alleles showed that DRB1*1301and DQB1*0602 had high specificity (94.2% and 90.1%) but low sensitivity (25.1% and 26.3%), respectively., Conclusion: It was suggested that specific HLA class II alleles (DRB1 and DQB1) were associated with antibody response to HepB., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite an effective vaccine, measles remains a major health problem globally, particularly in developing countries. More than 30% of children show primary vaccine failure and therefore remain vulnerable to measles. Genetic variation in key innate pathogen recognition receptors, such as the measles cell entry receptors CD46 and SLAM, measles attachment receptor DC-SIGN, the antiviral toll-like receptors (TLR)3, TLR7 and TLR8, and the cytosolic antiviral receptor RIG-I, may significantly affect measles IgG antibody responses. Measles is still highly prevalent in developing countries such as those in Africa however there is no previous data on the effect of these innate immune genes in a resident African population. Polymorphisms (n=29) in the candidate genes were genotyped in a cohort of vaccinated children (n=238) aged 6 months-14 years from Mozambique, Africa who either had vaccine failure and contracted measles (cases; n=66) or controls (n=172). Contrasting previous associations with measles responses in Caucasians and/or strong evidence for candidacy, we found little indication that these key innate immune genes affect measles IgG responses in our cohort of Mozambican children. We did however identify that CD46 and TLR8 variants may be involved in the occurrence of measles vaccine failure. This study highlights the importance of genetic studies in resident, non-Caucasian populations, from areas where determining the factors that may affect measles control is of a high priority., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Several lines of evidence have supported a host genetic contribution to vaccine response, but genome-wide assessments for specific determinants have been sparse. Here we describe a genome-wide association study (GWAS) of protective antigen-specific antibody (AbPA) responses among 726 European-Americans who received Anthrax Vaccine Adsorbed (AVA) as part of a clinical trial. After quality control, 736,996 SNPs were tested for association with the AbPA response to 3 or 4 AVA vaccinations given over a 6-month period. No SNP achieved the threshold of genome-wide significance (p=5 × 10(-8)), but suggestive associations (p<1 × 10(-5)) were observed for SNPs in or near the class II region of the major histocompatibility complex (MHC), in the promoter region of SPSB1, and adjacent to MEX3C. Multivariable regression modeling suggested that much of the association signal within the MHC corresponded to previously identified HLA DR-DQ haplotypes involving component HLA-DRB1 alleles of *15:01, *01:01, or *01:02. We estimated the proportion of additive genetic variance explained by common SNP variation for the AbPA response after the 6 month vaccination. This analysis indicated a significant, albeit imprecisely estimated, contribution of variation tagged by common polymorphisms (p=0.032). Future studies will be required to replicate these findings in European Americans and to further elucidate the host genetic factors underlying variable immune response to AVA., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We performed a genome-wide association study (GWAS) of antibody levels in a multi-ethnic group of 1071 healthy smallpox vaccine recipients. In Caucasians, the most prominent association was found with promoter SNP rs10489759 in the LOC647132 pseudogene on chromosome 1 (p=7.77×10(-8)). In African-Americans, we identified eight genetic loci at p<5×10(-7). The SNP association with the lowest p-value (rs10508727, p=1.05×10(-10)) was in the Mohawk homeobox (MKX) gene on chromosome 10. Other candidate genes included LOC388460, GPR158, ZHX2, SPIRE1, GREM2, CSMD1, and RUNX1. In Hispanics, the top six associations between genetic variants and antibody levels had p-values less than 5×10(-7), with p=1.78×10(-10) for the strongest statistical association (promoter SNP rs12256830 in the PCDH15 gene). In addition, SNP rs4748153 in the immune response gene PRKCQ (protein kinase C, theta) was significantly associated with neutralizing antibody levels (p=2.51×10(-8)). Additional SNP associations in Hispanics (p≤3.40×10(-7)) were mapped to the KIF6/LOC100131899, CYP2C9, and ANKLE2/GOLGA3 genes. This study has identified candidate SNPs that may be important in regulating humoral immunity to smallpox vaccination. Replication studies, as well as studies elucidating the functional consequences of contributing genes and polymorphisms, are underway., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The magnitude of the immune response to vaccinations can be influenced by genetic variability. In the present study, we aimed to investigate whether cytokine or cytokine receptor gene polymorphisms were associated with variations in the immune response to childhood vaccination. The study group consisted of 141 healthy infants who had been immunized with hepatitis B vaccine (HBV), 7-valent pneumococcal conjugate (PCV7), and diphtheria, tetanus, acellular pertussis (DTaP) vaccines according to standard childhood immunization schedules. Genotype analysis was performed on genomic DNA using a 5' nuclease PCR assay. Post vaccination total, isotypic, and antigen-specific serum antibody levels were measured using multiplex immunoassays. Significant associations were observed between SNPs in the TNFalpha, IL-12B, IL-4Ralpha, and IL-10 genes and vaccine-specific immune responses (p<0.05). In addition, SNPs in the IL-1beta, TNFalpha, IL-2, IL-4, IL-10, IL-4Ralpha, and IL-12B genes were associated with variations in serum levels of immunoglobulins (IgG, IgA, IgM) and IgG isotypes (IgG1-IgG3) (p<0.05). These data suggest that genetic variations in cytokine genes can influence vaccine-induced immune responses in infants, which in turn may influence vaccine efficacy.

Purported genetic associations found in population studies require validation for confirmation. We previously reported rubella vaccine-induced immune responses and HLA associations in 346 adolescents, age 12-18 years (1st cohort), following two doses of a rubella-containing vaccine. We sought to replicate the associations discovered in that work by verifying these associations in a new cohort of 396 subjects, age 11-19 years (2nd cohort), all having had two doses of a rubella-containing vaccine. We found that B*2705 (median 1st cohort 20.9 IU/ml, p=0.028; 2nd cohort 20.5 IU/ml, p=0.001) and DPA1*0201 (median 1st cohort 32.5 IU/ml, p=0.048; 2nd cohort 25.8 IU/ml, p=0.025) alleles were consistently associated with lower rubella-induced antibodies. Further, DPB1*0401 (median 1st cohort 43.5 IU/ml, p=0.021; 2nd cohort 36.2 IU/ml, p=0.002) alleles were associated with higher antibody levels in both populations. The association of DRB1*04-DQB1*03-DPB1*03 (mean 1st cohort 25.2 IU/ml, p=0.011; 2nd cohort 21.4 IU/ml, p=0.032) and DRB1*15/16-DQB1*06-DPB1*03 (1st cohort 16.3 IU/ml, p=0.043; 2nd cohort 19.1 IU/ml, p=0.023) haplotypes with lower rubella-specific antibodies was observed in both studies. This study provides confirmatory evidence for an association between specific class I and II HLA markers and haplotypes with rubella vaccine-induced humoral responses and lends further weight to their influence on rubella immune responses.

Seasonal influenza causes significant morbidity, mortality, and economic costs. Vaccines against influenza, though both safe and effective, are imperfect. Notably, these vaccines result in significant immune response variability across the population. The mechanism for this variability, in part, appears to lie in the polymorphisms of key immune response genes. Despite the importance of this variability, little in the way of genetic polymorphisms and its association with vaccine immune response to viral vaccines has been performed. Herein, we review and synthesize what is known about the immune response pathway and influenza viral immunity and then present original data from our laboratory on the immunogenetic relationships between HLA, cytokine and cytokine receptor gene polymorphisms and the variations in humoral immune response to inactivated seasonal influenza vaccine. Finally, we propose that a better understanding of vaccine immunogenetics offers insight towards the development of better influenza vaccines.

N-linked glycosylations of viral proteins have been implicated in immunogenicity. In this study, the effects of the N-linked glycosylation of the hepatitis C virus (HCV) E1 protein, a naturally poor immunogen, on the induction of specific immune response were examined. We constructed the plasmids containing the genes encoding both wild type and mutant E1 proteins in which N-linked glycosylation sites are mutated individually or in combination by site-directed mutagenesis. The immunogenicity of wild type E1 and six mutated E1 proteins was analyzed in BALB/C mice using a DNA-based vaccination approach. We found that E1-M2 mutant (at site of N209SS) significantly enhanced E1-specific CD8(+)T cells cytotoxic T lymphocytes (CTL) activities, expression of IFN-gamma producing T cells, and suppression of tumor growth. While E1-M4 mutant (at site of N305CS) induced the highest specific antibody response among all groups. Moreover, E1 wild-type vaccinated mice developed a mixture of IgG1 and Ig2a, but E1-M2 mutant induced only IgG2a isotype, and E1-M4 mutant dominantly developed IgG1 isotype. Our data showed that N-linked glycosylation can limit both cellular and antibody response to the HCV E1 protein and deletion of the N-glycosylation sites at N209SS and N305CS of hepatitis C virus envelope protein E1 provided potential applications for the development of DNA vaccine with enhanced immunogenicity.

Plasmid-based IL-12 has been demonstrated to successfully enhance the immunogenicity of DNA vaccines, thus enabling a reduction of the amount of DNA required for immunization. IL-15 is thought to affect the maintenance and enhance effector function of CD8(+) memory T cells. Since the ability to elicit a long-term memory response is a desirable attribute of a prophylactic vaccine, we sought to evaluate the ability of these plasmid-based cytokines to serve as vaccine adjuvants in rhesus macaques. Macaques were immunized with plasmid DNA encoding SIVgag in combination with plasmid IL-12, IL-15, or a combination of IL-12 and IL-15. The plasmid-based cytokines were monitored for their ability to augment SIVgag-specific cellular and humoral immune responses and to alter the clinical outcome following pathogenic SHIV(89.6P) challenge. Macaques receiving SIVgag pDNA in combination with plasmid IL-12 alone, or in combination with plasmid IL-12 and IL-15, demonstrated significantly elevated cell-mediated and humoral immune responses resulting in an improved clinical outcome following virus challenge compared to macaques receiving SIVgag pDNA alone. Macaques receiving SIVgag pDNA in combination with plasmid IL-15 alone demonstrated minor increases in cell-mediated and humoral immune responses, however, the clinical outcome following virus challenge was not improved. These results have important implications for the continued development of plasmid DNA vaccines for the prevention of HIV-1 infection.

In this report, we describe a short peptide, containing a T helper- and a B-cell epitope, located in the Gag protein of the caprine arthritis encephalitis virus (CAEV). This T-cell epitope is capable of inducing a robust T-cell proliferative response in vaccinated goats with different genetic backgrounds and to provide help for a strong antibody response to the B-cell epitope, indicating that it may function as a universal antigen-carrier for goat vaccines. The primary immune response of goats homozygous for MHC class I and II genes showed an MHC-dependent partitioning in rapid-high and slow-low responses, whereas the memory immune response was strong in both groups, demonstrating that a vaccine based on this immunodominant T helper epitope is capable to overcome genetic differences.

There is an ever-growing interest in plant molecular farming as a system for producing valuable recombinant pharmaceutical molecules, such as single-chain variable fragments, on an industrial/agricultural scale and it appears that it is going to become a reality. Human epidermal growth factor receptor-2 (HER2) is an oncogene involved in abnormal cell growth in breast cancer and is considered for the development of new cancer therapies. We describe here the cloning and expression of a scFv-alpha HER2 that has been produced in Escherichia coli and in plants using both stable and transient systems in tobacco and Nicotiana benthamiana. Single-chain antibodies (ScFvs) extracted and purified from E. coli and plant tissues were tested for functionality and specificity by flow cytometry analysis on several cell lines and showed positive results when used on breast cancer slides coming from human frozen tissues. As a result, scFv-alpha HER2 represents a good opportunity for application and use in diagnosis and therapy.

Several reports have indicated that combinatorial regimens with DNA and protein vaccines can elicit both strong immune responses, to circumvent the limits of each vaccine. Surprisingly little was known on HBV vaccine. Here, we investigated the immunization effects of several regimens in BALB/c mice. The level of total antibody and isotypes of IgG were determined by ELISA. Cellular immune responses were assayed by measuring the production of cytokines and CTL activity after re-stimulation for 7 days in vitro with tumor cells CT26/S stably expressing HBsAg. The efficacy of immunoprotection against the challenge of transplanted CT26/S was also examined. The regimen involving twice priming pVAX(S) encoding HBsAg and once recombinant HBsAg protein (rHBsAg) boosting, induced strong and homogenous antibody responses. This regimen induced significant stronger responses of interleukin-12 and gamma interferon (IFN-gamma) in splenocytes, and elicited stronger CD8+ CTL responses and greater immunopretectional efficacy than those elicited by immunization with rHBsAg or pVAX(S) alone. Our regimen may thus provide a strategy for developing an improved immunization against HBV and many other pathogens.

About 10% of health care professionals vaccinated against hepatitis B virus (HBV) fail to develop protective antibodies. We tested the capacity of peripheral blood lymphocytes from 121 health care professionals, including 76 non-responders, to proliferate to four HBV vaccines, examined the proliferating cells' subset, production of IFN-gamma, IL-4 and IL-10, and for 22 subjects, the cytokine production genotype. Specific proliferative responses to at least one HBV antigen were noted in 75% humoral non-responders. These cells differed from the CD4+ strongly proliferating cells of responders. Non-responders frequently displayed a genotype of high TGF-beta and intermediate IL-10 secretion. Most humoral non-responders to HBV thus develop specific cellular immune responses, eventually liable to protect them against viral infection.

Presently, commercially available cell culture rabies vaccines for humans and animals consist of the five inactivated rabies virus proteins. The vaccines elicit a CD4+ helper T-cell response and a humoral B-cell response against the viral glycoprotein (G) resulting in the production of virus neutralizing antibody. Antibody against the viral nucleoprotein (N) is also present, but the mechanism(s) of its protection is unclear. HIV-infected individuals with low CD4+ T-lymphocyte counts and individuals undergoing treatment with immunosuppressive drugs have an impaired neutralizing antibody response after pre- and post-exposure immunization with rabies cell culture vaccines. Here we show the efficacy of live vaccinia-rabies virus recombinants, but not a cell culture vaccine consisting of inactivated rabies virus, to elicit elevated levels of neutralizing antibody in B-lymphocyte deficient A/WySnJ mice. The cell culture vaccine also failed to protect the mice, whereas a single immunization of a vaccinia recombinant expressing the rabies virus G or co-expressing G and N equally protected the mice up to 18 months after vaccination. The data suggest that recombinant poxviruses expressing the rabies virus G, in particular replication defective poxviruses such as canarypox or MVA vaccinia virus that undergo abortive replication in non-avian cells, or the attenuated vaccinia virus NYVAC, should be evaluated as rabies vaccines in immunocompromised individuals.

DNA vaccines have been effective at generating useful immune responses in many animal species. However, it is clearly desirable to increase their potency. The identification of adjuvants that increase their cell-mediated immune (CMI) response is therefore an important goal. Resiquimod is an imiquimod analog proven to activate dendritic cells through TLR-7. The adjuvant capacity of resiquimod has not, to our knowledge, been studied in the context of genetic immunization. Here, we studied resiquimod as an adjuvant for plasmid vaccine therapy by intra-muscular immunization of BALB/c mice with HIV-1 gag DNA vaccine without and with several concentrations of resiquimod (ranging from 5-100nM). We observed that resiquimod moderately enhanced IFN-gamma production as measured by a peptide-based ELISPOT assay compared to that obtained in mice immunized with DNA gag only. Antigen-specific T-cell proliferation studies showed a several-fold increase in the stimulation index in mice immunized with DNA gag +50 nM of resiquimod as compared to mice receiving DNA gag alone. Antibody titer also increased, while the antibody isotyping data showed a strong Th1 biased type response. Analysis of cytokine production in serum samples demonstrated a stronger Th1 cytokine bias in the presence of resiquimod. Furthermore, relevant increase in IL-4 production, as measured by ELISPOT assay, was not observed. Our results show that resiquimod can have modest adjuvant activity, in a DNA formulation, driving the immune system towards a cell-mediated immune response. Additional studies involving this adjuvant for DNA vaccines are underway.

Considerable variability exists in the vaccine response to hepatitis B with 5-10% of healthy young adults demonstrating no or inadequate responses following a standard vaccination schedule. As the interleukin-1beta (IL-1beta) cytokine has been shown to be important in the development of immune responses, we determined whether vaccine efficacy is influenced by genetic polymorphisms associated with IL-1beta expression. Ninety-two healthy individuals who were negative for antibodies to hepatitis B antigen (anti-HBs) were vaccinated against hepatitis B according to a standardized schedule. At selected times, antibody titers and lymphoproliferative capacity to hepatitis B surface antigen (HBsAg) were determined. DNA genotyping for IL-1beta polymorphisms using a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique demonstrated that both the anti-HBs titer and the T-cell lymphoproliferative response to HBsAg are significantly increased in individuals possessing the IL-1beta (+3953) minor allelic variant., (Copyright 2002 Elsevier Science Ltd.)

Context: Estimating the magnitude of the genetic contribution to the overall variation of antibody levels among individuals should help clarify the role of genetic association in the biological mechanism of vaccine response and failure. This, in turn, should help guide the design of improved vaccines with enhanced efficacy., Objective: To explore the magnitude of genetic influence on antibody levels following measles, mumps and rubella vaccines., Design: Cross-sectional survey study., Setting: Olmsted County, Minnesota., Participants: Healthy twin-pairs. Of the 100 twin-pairs enrolled, 45 were monozygotic., Interventions: Determinations of zygosity, vaccine status, and quantitative IgG to measles, mumps, and rubella., Main Outcome Measure: Heritability (ratio of genetic variance to total variance)., Results: The number of vaccine-doses, the age at initial immunization, and the time between immunization and sampling did not differ between monozygotic and dizygotic twin pairs. The genetic variance - the variance in antibody levels presumably due to genetic effects - was 0.49 for measles, 0.54 for mumps, and 0.13 for rubella. Heritability, the ratio of genetic variance to total variance, was 88.5% for measles, with the lower bound of a one-sided 95% confidence interval equal to 52.4%. The heritability was, for mumps, 38.8% with a lower bound of 1.60%. The heritability for rubella was 45.7% with a lower bound of 4.94%., Conclusion: Our data support the concept that genetic influences play a substantial role in the variation of antibody levels following immunization against measles and, to a lesser extent, mumps and rubella.

Sixty bulls were tested for antibodies to the heterologous serotype C1 of FMDV following repeatable vaccinations with a commercial trivalent vaccine (O1, A22, Asia1). Six (10%) bulls were found to possess rather high levels of heterologous neutralizing antibodies which showed accumulative trend with age. Two high positive and two negative bulls for the heterologous serotype C1 were selected for progeny test involving ten daughters of each bull. The four bulls, either positive or negative for the heterologous serotype C1, showed significant phenotypic correlation between their heterologous and homologous titers (O1, A22, Asia1). This correlation between heterologous and homologous antibody titers was not found in the daughters of these bulls. However, two of ten daughters of one positive bull, to C1 showed individual high titers (> or = 1.5). The intradermal (ID) as compared to subcutaneous (SC) route of administration resulted in higher rate of responders to both heterologous serotypes C1 and SAT1. The heterologous immune response to FMDV in Israeli-Friesian cattle was found to be related to the age of the host, multiplicity of vaccinations, route of vaccination, kind and numbers of the antigens used in the vaccine. The homologous immune response is also controlled by genetic factors.

The transporter associated with antigen processing (TAP) gene products transport peptides from the cytosol to the endoplasmic reticulum for processing by the immune system. We hypothesized that polymorphisms within the TAP genes may influence measles vaccine antigen processing and hence antibody response. TAP genotypes were determined for subjects who were measles vaccine nonresponders (n = 32) and hyper-responders (n = 28). TAP1 and TAP2 alleles were determined by PCR amplification of specific alleles (PASA). Measles vaccine nonresponders were more likely to be homozygous at TAP2 position 665 than were hyper-responders (OR = 5.0, P = 0.016). Lastly, a trend was found in the overall distribution of all TAP2 genotype frequencies between hyper-responders and nonresponders (P = 0.08). No association was found between TAP1 polymorphisms and vaccine response. These data reveal an association between TAP2 genotype and measles vaccine antibody response which may explain one mechanism behind vaccine failure.