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 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.