Extinction of the Human Leukocyte Antigen Homozygosity Effect After Two Doses of the Measles-Mumps-Rubella Vaccine (original) (raw)
Related papers
The Journal of Infectious Diseases, 2006
To elucidate the contribution of human leukocyte antigen (HLA) haplotypes and their genotypic combinations to immune status after measles-mumps-rubella (MMR) vaccination, 346 children 12-18 years of age were studied. The class I A*29-Cw*16-B*44 haplotype was associated with lower levels of immunoglobulin G (IgG) antibody to both measles ( ) and mumps ( ) viral antigens. The A*26-Cw*12-B*38 haplotype P p .08 P p .03 was associated with higher cellular immune responses to measles ( ) and mumps ( ) vaccine P p .02 P p .01 viruses. Subjects with the class II DRB1*03-DQB1*02-DPB1*04 haplotype had higher lymphoproliferative responses to measles virus ( ) and mumps virus ( ). The DRB1*15/16-DQB1*06-DPB1*03 hap-P p .01 P p .006 lotype was associated with high levels of IgG antibody to measles virus ( ) but low levels of IgG antibody P p .09 to rubella virus ( ), whereas DRB1*04-DQB1*03-DPB1*03 was associated with high lymphoproliferative P p .02 responses to both measles ( ) and rubella ( ) vaccine viruses. A*26-Cw*12-B*38 was associated P p .01 P p .002 with both mumps virus-specific humoral ( ) and cell-mediated ( ) immune responses after 2 P p .007 P p .01 doses of MMR vaccine. Haplotype DRB1*04-DQB1*03-DPB1*03 was associated with both lower rubella virus IgG antibody levels ( ) and higher rubella virus-specific lymphoproliferation ( ). Better char-P p .02 P p .002 acterization of such HLA profiles could inform and improve the design of novel epitope-rich vaccines and help to predict protective immune responses at the individual and population level.
HLA homozygosity does not adversely affect measles vaccine-induced cytokine responses
Virology, 2007
The association between HLA homozygosity and measles-specific Th 1 (IFN-γ, IL-2 and IL-12p40) and Th 2 (IL-4 and IL-10) cytokine responses were assessed in a group of 339 healthy schoolchildren 12-18 years of age previously immunized with two doses of live-attenuated measles virus vaccine. No associations were observed between class I HLA homozygosity and measles-specific cytokine levels. Children who were homozygous at the class II DRB1, DQA1, DPA1 and DPB1 loci had higher median IFN-γ secretion levels compared with children who were heterozygous for DRB1 (77.7 vs. 39.5 pg/ml, p = 0.05), DQA1 (60.9 vs. 36.6 pg/ml, p = 0.03), DPA1 (46.1 vs. 27.1 pg/ml, p = 0.01) and DPB1 (61.5 vs. 36.0 pg/ml, p = 0.01) loci, respectively. Homozygosity at increasing numbers of HLA loci ( > =4) was associated with increased IFN-γ secretion levels (test for trend p-value = 0.01). Our results suggest that HLA homozygosity showed no disadvantage for measles-specific cytokine responses and instead was associated with increased IFN-γ levels.
Vaccine, 2004
Associations between human leukocyte antigen (HLA) genes and very high levels of antibodies (or hyperseroresponsiveness) to measles antigens in a genetically heterogeneous human population are poorly understood. We studied the association between antibody levels after measles vaccination and HLA class I and II alleles among 170 US schoolchildren who received one dose of measles-mumps-rubella II vaccine. Vaccine recipients were divided into two groups: 93 recipients who were seropositive and 77 recipients who were hyperseropositive (the upper 10th percentile of antibody levels of all subjects). Out of all the alleles analyzed, HLA-B(*)7 (odds ratio (OR) 1.9; P = 0.05), DQA1(*)0104 (OR 4.6; P = 0.02) and DPA1(*)0202 (OR 4.8; P = 0.04) alleles were positively associated with hyperseropositivity, whereas HLA-B(*)44 (OR 0.4; P = 0.02), DRB1(*)01 (OR 0.6; P = 0.09), DRB1(*)08 (OR 0.3; P = 0.04), DQB1(*)0301 (OR 0.5; P = 0.04), and DPB1(*)0401 (OR 0.6; P = 0.03) alleles were negatively ass...
Vaccine, 2001
This is the first large cohort study to report a genetic association between humoral antibody level after measles vaccine and the HLA class II genes. The WHO goal to eradicate measles world-wide magnifies the importance of data relating to the influence of immunogenetics on measles vaccine-induced antibody responses. We present here the analysis of 242 individuals who received one dose of measles-mumps-rubella-II (MMR-II) vaccine at the age of 15 months and were genotyped for HLA class II alleles. These subjects fit into one of three categories; 72 were classified as seronegative, 93 were seropositive and 77 were serohyperpositive. HLA-DRB1 * 03 (odds ratio (OR), 2.22) and HLA-DPA1 * 0201 (OR, 1.71) were significantly associated with measles vaccine seronegativity, while additional alleles provided suggestive evidence of association with seronegativity: DQA1 * 0201, DQB1 * 0201, and DQA1 * 0501. The alleles DRB1 * 03 and DQA1 * 0201 remained statistically significant after accounting for the effects of other alleles. These findings are crucial in designing both measles eradication by the use of vaccine, and future vaccines to be used in genetically heterozygous populations.
Consistency of HLA associations between two independent measles vaccine cohorts: A replication study
Vaccine, 2012
Associations between HLA genotypes and measles vaccine humoral and cellular immune responses were examined to better understand immunogenetic drivers of vaccine response. Two independent study cohorts of healthy schoolchildren were examined: cohort one, 346 children between 12-18 years of age; and cohort two, 388 children between 11-19 years of age. All received two age-appropriate doses of measles-containing vaccine. The purpose of this study was to identify and replicate associations between HLA genes and immune responses following measles vaccination found in our first cohort. Associations of comparable magnitudes and with similar p-values were observed between B*3503 (1 st cohort p=0.01; 2 nd cohort p=0.07), DQA1*0201 (1 st cohort p=0.03; 2 nd cohort p=0.03), DQB1*0303 (1 st cohort p=0.10; 2 nd cohort p=0.02), DQB1*0602 (1 st cohort p=0.07; 2 nd cohort p=0.10), and DRB1*0701 (1 st cohort p=0.03; 2 nd cohort p=0.07) alleles and measles-specific antibody levels. Suggestive, yet consistent, associations were observed between the B7(1 st cohort p=0.01; 2 nd cohort p=0.08) supertype and higher measles antibody levels in both cohorts. Also, in both cohorts, the B*0801 and DRB1*0301 alleles, C*0802 and DPA1*0202 alleles, and DRB1*1303 alleles displayed consistent associations with variations in IFN-γ, IL-2 and IL-10 secretion, respectively. This study emphasizes the importance of replicating HLA associations with measles vaccine-induced humoral and cellular immune responses and increases confidence in the results. These data will inform strategies for functional studies and novel vaccine development, including epitope-based measles vaccines. This is the first HLA association replication study with measles vaccine-specific immune responses to date.
Immunogenetics, 2005
Measles virus-specific T cells and the production of cytokines play a critical role in the immune response following measles immunization. To understand the genetic factors that influence variation in IFN-γ and IL-4 responses following measles immunization and to provide insight into the factors influencing both cellular and humoral immunity to measles, we assessed associations between human leukocyte antigen (HLA) class II genes and measles-specific Th1 and Th2-type cytokine responses in peripheral blood lymphocytes from 339 children previously vaccinated with two doses of measlesmumps-rubella vaccine (MMR-II). Median values for measles-specific IFN-γ and IL-4 secretion levels were 40.73 and 9.71 pg/ml, respectively. The global tests suggested associations between measles-specific IFN-γ response and alleles of the DRB1 and DQB1 loci (P=0.07 and P=0.02, respectively). Specifically, DRB1*0301, *0901, and *1501 alleles were significantly associated with IFN-γ secretion. The alleles that suggested evidence of an HLA association with IL-4 secretion were DRB1*0103, *0701, and *1101. Th1 cytokine responses and DQB1 allele associations revealed that the alleles with the strongest association with IFN-γ secretion were DQB1*0201, *0303, *0402, and *0602. Specific alleles with a suggestive association with low measles-specific Th2 cytokine responses were DQB1*0202 and *0503. In addition, DPB1*0101, *0201, and *0601 alleles provided suggestive evidence of an HLA association with measles-induced IFN-γ response, while DPB1*0501 was associated with an IL-4 response. These data suggest that IFN-γ and IL-4 cytokine responses to measles may be genetically restricted in part by HLA class II genes, which in turn can restrict the cellular immune response to measles vaccine.
PloS one, 2017
Human antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to viral antigens. To expand on and improve our previous work with HLA genes, and to explore the genetic contribution of KIR genes to the inter-individual variability in measles vaccine-induced antibody responses, we performed a large population-based study in 2,506 healthy immunized subjects (ages 11 to 41 years) to identify HLA and KIR associations with measles vaccine-induced neutralizing antibodies. After correcting for the large number of statistical tests of allele effects on measles-specific neutralizing antibody titers, no statistically significant associations were found for either HLA or KIR loci. However, suggestive associations worthy of follow-up in other cohorts include B*57:01...