TY - JOUR
T1 - Genetic associations with measles PRNT and IgG antibody response to MMR vaccination in 6- and 15-month-old children
AU - Sørensen, Jesper Kiehn
AU - Jensen, Andreas
AU - Zimakoff, Anne Cathrine
AU - Vittrup, Dorthe Maria
AU - Malon, Michelle
AU - Kim, Sejun
AU - Hatley, Emma Victoria
AU - Bybjerg-Grauholm, Jonas
AU - Kaur, Simranjeet
AU - Pociot, Flemming
AU - Stensballe, Lone Graff
AU - Svensson, Jannet
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025
Y1 - 2025
N2 - Background: Measles immunization is a cornerstone in public health, yet vaccine failure affects up to 10 % of the population, leaving some vaccinated individuals susceptible to infection. Many factors influence vaccine responses, and we hypothesize that host genetic factors impact vaccine response to measles, mumps, and rubella (MMR) vaccination. Methods: We performed Human Leukocyte Antigen (HLA) associations and a genome-wide association study of measles plaque reduction neutralization test (PRNT) and Immunoglobin G (IgG) in 607 infants from a randomized, double-blind vaccine trial of the MMR vaccine. We examined HLA and Single Nucleotide Polymorphism (SNP) associations with measles vaccine response at 5–7 months and again at 15 months. Association analyses for SNPs were performed using linear and logistic regression, while HLA associations only utilized linear regression. Results: Two novel regions associated with post-vaccine measles PRNT levels were identified - one on chromosome 1 and one on chromosome 9. The most significant SNP at chromosome 9 is the intronic SNP rs77498152 within the LINGO2-gene (p-value = 1.1∙10−9), and on chromosome 1, the intronic SNP rs3005891 (p-value = 2.2∙10−8) in the LOC124904186 gene. Associations of 4-digit HLA type alleles and measles PRNT revealed the HLA-A*2902 (p = 0.006) and measles IgG HLA-B*1801 (p = 0.0025) as the most strongly associated HLA types; both were associated with a lower response. Conclusion: In an MMR vaccine trial, this study identified novel genetic regions on chromosomes 1 and 9 associated with measles PRNT in healthy infants. Four-digit HLA types were associated with both Measles IgG and PRNT. Associations between SNPs and HLA have been investigated previously, and we suspect the difference in results is due to dissimilarities between cohorts and study design, especially regarding participants' age and time from immunization to immune outcome measurement.
AB - Background: Measles immunization is a cornerstone in public health, yet vaccine failure affects up to 10 % of the population, leaving some vaccinated individuals susceptible to infection. Many factors influence vaccine responses, and we hypothesize that host genetic factors impact vaccine response to measles, mumps, and rubella (MMR) vaccination. Methods: We performed Human Leukocyte Antigen (HLA) associations and a genome-wide association study of measles plaque reduction neutralization test (PRNT) and Immunoglobin G (IgG) in 607 infants from a randomized, double-blind vaccine trial of the MMR vaccine. We examined HLA and Single Nucleotide Polymorphism (SNP) associations with measles vaccine response at 5–7 months and again at 15 months. Association analyses for SNPs were performed using linear and logistic regression, while HLA associations only utilized linear regression. Results: Two novel regions associated with post-vaccine measles PRNT levels were identified - one on chromosome 1 and one on chromosome 9. The most significant SNP at chromosome 9 is the intronic SNP rs77498152 within the LINGO2-gene (p-value = 1.1∙10−9), and on chromosome 1, the intronic SNP rs3005891 (p-value = 2.2∙10−8) in the LOC124904186 gene. Associations of 4-digit HLA type alleles and measles PRNT revealed the HLA-A*2902 (p = 0.006) and measles IgG HLA-B*1801 (p = 0.0025) as the most strongly associated HLA types; both were associated with a lower response. Conclusion: In an MMR vaccine trial, this study identified novel genetic regions on chromosomes 1 and 9 associated with measles PRNT in healthy infants. Four-digit HLA types were associated with both Measles IgG and PRNT. Associations between SNPs and HLA have been investigated previously, and we suspect the difference in results is due to dissimilarities between cohorts and study design, especially regarding participants' age and time from immunization to immune outcome measurement.
U2 - 10.1016/j.vaccine.2025.126788
DO - 10.1016/j.vaccine.2025.126788
M3 - Journal article
C2 - 39914254
AN - SCOPUS:85216829505
VL - 50
JO - Vaccine
JF - Vaccine
SN - 0264-410X
M1 - 126788
ER -