Consistency of HLA associations between two independent measles vaccine cohorts: A replication study

Inna G. Ovsyannikova; V. Shane Pankratz; Robert A. Vierkant; Robert M. Jacobson; Gregory A. Poland

doi:10.1016/j.vaccine.2012.01.038

Consistency of HLA associations between two independent measles vaccine cohorts: A replication study

Inna G. Ovsyannikova, V. Shane Pankratz, Robert A. Vierkant, Robert M. Jacobson, Gregory A. Poland

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33 Scopus citations

Abstract

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 and 18 years of age; and cohort two, 388 children between 11 and 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 (1st cohort p= 0.01; 2nd cohort p= 0.07), DQA1*0201 (1st cohort p= 0.03; 2nd cohort p= 0.03), DQB1cellular0303 (1st cohort p= 0.10; 2 cohort p= 0.02), DQB1*0602 (1st cohort p= 0.07; 2nd cohort p= 0.10), and DRB1*0701 (1st cohort p= 0.03; 2nd cohort p= 0.07) alleles and measles-specific antibody levels. Suggestive, yet consistent, associations were observed between the B7 (1st cohort p= 0.01; 2nd 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.

Original language	English (US)
Pages (from-to)	2146-2152
Number of pages	7
Journal	Vaccine
Volume	30
Issue number	12
DOIs	https://doi.org/10.1016/j.vaccine.2012.01.038
State	Published - Mar 9 2012

Keywords

Antibodies
Cytokines
HLA genotypes
Haplotypes
Measles vaccine
Replication study

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2012.01.038

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title = "Consistency of HLA associations between two independent measles vaccine cohorts: A replication study",

abstract = "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 and 18 years of age; and cohort two, 388 children between 11 and 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 (1st cohort p= 0.01; 2nd cohort p= 0.07), DQA1*0201 (1st cohort p= 0.03; 2nd cohort p= 0.03), DQB1cellular0303 (1st cohort p= 0.10; 2 cohort p= 0.02), DQB1*0602 (1st cohort p= 0.07; 2nd cohort p= 0.10), and DRB1*0701 (1st cohort p= 0.03; 2nd cohort p= 0.07) alleles and measles-specific antibody levels. Suggestive, yet consistent, associations were observed between the B7 (1st cohort p= 0.01; 2nd 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.",

keywords = "Antibodies, Cytokines, HLA genotypes, Haplotypes, Measles vaccine, Replication study",

author = "Ovsyannikova, {Inna G.} and {Shane Pankratz}, V. and Vierkant, {Robert A.} and Jacobson, {Robert M.} and Poland, {Gregory A.}",

note = "Funding Information: We thank the Mayo Clinic Vaccine Research Group staff and subjects who participated in our studies. We thank Megan M. O{\textquoteright}Byrne and Caroline L. Vitse for their help with this manuscript. This work was supported by NIH grants AI 33144 , AI 48793 and 5UL1RR024150-03 from the National Center for Research Resources (NCRR) , a component of the National Institutes of Health, and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. ",

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doi = "10.1016/j.vaccine.2012.01.038",

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AU - Ovsyannikova, Inna G.

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AU - Vierkant, Robert A.

AU - Jacobson, Robert M.

AU - Poland, Gregory A.

N1 - Funding Information: We thank the Mayo Clinic Vaccine Research Group staff and subjects who participated in our studies. We thank Megan M. O’Byrne and Caroline L. Vitse for their help with this manuscript. This work was supported by NIH grants AI 33144 , AI 48793 and 5UL1RR024150-03 from the National Center for Research Resources (NCRR) , a component of the National Institutes of Health, and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

PY - 2012/3/9

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N2 - 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 and 18 years of age; and cohort two, 388 children between 11 and 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 (1st cohort p= 0.01; 2nd cohort p= 0.07), DQA1*0201 (1st cohort p= 0.03; 2nd cohort p= 0.03), DQB1cellular0303 (1st cohort p= 0.10; 2 cohort p= 0.02), DQB1*0602 (1st cohort p= 0.07; 2nd cohort p= 0.10), and DRB1*0701 (1st cohort p= 0.03; 2nd cohort p= 0.07) alleles and measles-specific antibody levels. Suggestive, yet consistent, associations were observed between the B7 (1st cohort p= 0.01; 2nd 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.

AB - 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 and 18 years of age; and cohort two, 388 children between 11 and 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 (1st cohort p= 0.01; 2nd cohort p= 0.07), DQA1*0201 (1st cohort p= 0.03; 2nd cohort p= 0.03), DQB1cellular0303 (1st cohort p= 0.10; 2 cohort p= 0.02), DQB1*0602 (1st cohort p= 0.07; 2nd cohort p= 0.10), and DRB1*0701 (1st cohort p= 0.03; 2nd cohort p= 0.07) alleles and measles-specific antibody levels. Suggestive, yet consistent, associations were observed between the B7 (1st cohort p= 0.01; 2nd 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.

KW - Antibodies

KW - Cytokines

KW - HLA genotypes

KW - Haplotypes

KW - Measles vaccine

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Consistency of HLA associations between two independent measles vaccine cohorts: A replication study

Abstract

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