Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors

Neelam Dhiman, Gregory A. Poland, Julie M Cunningham, Robert M. Jacobson, Inna G. Ovsyannikova, Robert A. Vierkant, Yanhong Wu, V. Shane Pankratz

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Background: Measles infection requires 2 cellular receptors, signaling lymphocyte activation molecule (SLAM) and CD46. Known and novel single nucleotide polymorphisms (SNPs) in SLAM and CD46 genes might influence the immune response to measles vaccine. Objective: We sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response. Methods: We genotyped known SNPs in SLAM and CD46 genes in 339 subjects vaccinated with 2 doses of measles-mumps-rubella vaccine. We also sequenced the measles virus-binding domains of SLAM and CD46 to identify novel SNPs. Results: Increased representation of minor alleles for rs3796504 and rs164288 in the SLAM gene was associated with an allele dose-related decrease (4-fold) in measles-specific antibodies. Heterozygous genotype TC for rs12076998 located in the untranslated region 33 bp upstream of the measles virus-binding domain of the SLAM gene was associated with higher median antibody levels (1991 vs 1467 IU/L, P = .01) compared with wild-type TT. Within the CD46 gene, the minor allele C for intronic SNP (rs11118580) was associated with an allele dose-related decrease in measles antibodies (1072 vs 1795 IU/L, P < .01). Decreases in minor allele counts for rs3796504, rs164288, and rs1118580 demonstrated a significant (P < .001) additive effect on measles-specific antibodies. Conclusion: Our data suggest that specific SNPs present in both the SLAM and CD46 genes are associated with measurable and significant variations in antibody response after measles vaccination. Clinical implications: Understanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.

Original languageEnglish (US)
Pages (from-to)666-672
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume120
Issue number3
DOIs
StatePublished - Sep 2007

Fingerprint

Measles Vaccine
Virus Receptors
Measles virus
Lymphocyte Activation
Humoral Immunity
Measles
Single Nucleotide Polymorphism
Alleles
Genes
Virus Attachment
Vaccines
Antibodies
Antibody Formation
Measles-Mumps-Rubella Vaccine
Untranslated Regions
Immunogenetics
Vaccination
Genotype

Keywords

  • CD46
  • Measles vaccine
  • measles virus receptors
  • signaling lymphocyte activation molecule
  • single nucleotide polymorphisms

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors. / Dhiman, Neelam; Poland, Gregory A.; Cunningham, Julie M; Jacobson, Robert M.; Ovsyannikova, Inna G.; Vierkant, Robert A.; Wu, Yanhong; Pankratz, V. Shane.

In: Journal of Allergy and Clinical Immunology, Vol. 120, No. 3, 09.2007, p. 666-672.

Research output: Contribution to journalArticle

Dhiman, Neelam ; Poland, Gregory A. ; Cunningham, Julie M ; Jacobson, Robert M. ; Ovsyannikova, Inna G. ; Vierkant, Robert A. ; Wu, Yanhong ; Pankratz, V. Shane. / Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors. In: Journal of Allergy and Clinical Immunology. 2007 ; Vol. 120, No. 3. pp. 666-672.
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T1 - Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors

AU - Dhiman, Neelam

AU - Poland, Gregory A.

AU - Cunningham, Julie M

AU - Jacobson, Robert M.

AU - Ovsyannikova, Inna G.

AU - Vierkant, Robert A.

AU - Wu, Yanhong

AU - Pankratz, V. Shane

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N2 - Background: Measles infection requires 2 cellular receptors, signaling lymphocyte activation molecule (SLAM) and CD46. Known and novel single nucleotide polymorphisms (SNPs) in SLAM and CD46 genes might influence the immune response to measles vaccine. Objective: We sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response. Methods: We genotyped known SNPs in SLAM and CD46 genes in 339 subjects vaccinated with 2 doses of measles-mumps-rubella vaccine. We also sequenced the measles virus-binding domains of SLAM and CD46 to identify novel SNPs. Results: Increased representation of minor alleles for rs3796504 and rs164288 in the SLAM gene was associated with an allele dose-related decrease (4-fold) in measles-specific antibodies. Heterozygous genotype TC for rs12076998 located in the untranslated region 33 bp upstream of the measles virus-binding domain of the SLAM gene was associated with higher median antibody levels (1991 vs 1467 IU/L, P = .01) compared with wild-type TT. Within the CD46 gene, the minor allele C for intronic SNP (rs11118580) was associated with an allele dose-related decrease in measles antibodies (1072 vs 1795 IU/L, P < .01). Decreases in minor allele counts for rs3796504, rs164288, and rs1118580 demonstrated a significant (P < .001) additive effect on measles-specific antibodies. Conclusion: Our data suggest that specific SNPs present in both the SLAM and CD46 genes are associated with measurable and significant variations in antibody response after measles vaccination. Clinical implications: Understanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.

AB - Background: Measles infection requires 2 cellular receptors, signaling lymphocyte activation molecule (SLAM) and CD46. Known and novel single nucleotide polymorphisms (SNPs) in SLAM and CD46 genes might influence the immune response to measles vaccine. Objective: We sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response. Methods: We genotyped known SNPs in SLAM and CD46 genes in 339 subjects vaccinated with 2 doses of measles-mumps-rubella vaccine. We also sequenced the measles virus-binding domains of SLAM and CD46 to identify novel SNPs. Results: Increased representation of minor alleles for rs3796504 and rs164288 in the SLAM gene was associated with an allele dose-related decrease (4-fold) in measles-specific antibodies. Heterozygous genotype TC for rs12076998 located in the untranslated region 33 bp upstream of the measles virus-binding domain of the SLAM gene was associated with higher median antibody levels (1991 vs 1467 IU/L, P = .01) compared with wild-type TT. Within the CD46 gene, the minor allele C for intronic SNP (rs11118580) was associated with an allele dose-related decrease in measles antibodies (1072 vs 1795 IU/L, P < .01). Decreases in minor allele counts for rs3796504, rs164288, and rs1118580 demonstrated a significant (P < .001) additive effect on measles-specific antibodies. Conclusion: Our data suggest that specific SNPs present in both the SLAM and CD46 genes are associated with measurable and significant variations in antibody response after measles vaccination. Clinical implications: Understanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.

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