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Profiling of measles-specific humoral immunity in individuals following two doses of MMR vaccine using proteome microarrays.

ABSTRACT: Comprehensive evaluation of measles-specific humoral immunity after vaccination is important for determining new and/or additional correlates of vaccine immunogenicity and efficacy.We used a novel proteome microarray technology and statistical modeling to identify factors and models associated with measles-specific functional protective immunity in 150 measles vaccine recipients representing the extremes of neutralizing antibody response after two vaccine doses.Our findings demonstrate a high seroprevalence of antibodies directed to the measles virus (MV) phosphoprotein (P), nucleoprotein (N), as well as antibodies to the large polymerase (L) protein (fragment 1234 to 1900 AA). Antibodies to these proteins, in addition to anti-F antibodies (and, to a lesser extent, anti-H antibodies), were correlated with neutralizing antibody titer and/or were associated with and predictive of neutralizing antibody response.Our results identify antibodies to specific measles virus proteins and statistical models for monitoring and assessment of measles-specific functional protective immunity in vaccinated individuals.

SUBMITTER: Haralambieva IH

PROVIDER: S-EPMC4379563 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Profiling of measles-specific humoral immunity in individuals following two doses of MMR vaccine using proteome microarrays.

Haralambieva Iana H IH Simon Whitney L WL Kennedy Richard B RB Ovsyannikova Inna G IG Warner Nathaniel D ND Grill Diane E DE Poland Gregory A GA

Viruses 20150310 3

<h4>Introduction</h4>Comprehensive evaluation of measles-specific humoral immunity after vaccination is important for determining new and/or additional correlates of vaccine immunogenicity and efficacy.<h4>Methods</h4>We used a novel proteome microarray technology and statistical modeling to identify factors and models associated with measles-specific functional protective immunity in 150 measles vaccine recipients representing the extremes of neutralizing antibody response after two vaccine dos ...[more]

PMID: 25763865

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Project description:Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella (MMR) vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction for FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and African-Americans.

Dataset Information

Profiling of measles-specific humoral immunity in individuals following two doses of MMR vaccine using proteome microarrays.

Publications

Profiling of measles-specific humoral immunity in individuals following two doses of MMR vaccine using proteome microarrays.

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