Genetic associations with a fever after measles-containing vaccines

ABSTRACT

Children have elevated fever risk 1 to 2 weeks after the first dose of a measles-containing vaccine (MCV), which is likely affected by genetic, immunologic, and clinical factors. Fever after MCV is associated with febrile seizures, though may also be associated with higher measles antibody titers. This exploratory study investigated genetic and immunologic associations with a fever after MCV. Concurrent with a randomized Phase 3 clinical trial of 12–15-month-olds who received their first measles-mumps-rubella (MMR) vaccine in which parents recorded post-vaccination temperatures daily, we consented a subset to collect additional blood and performed human leukocyte antigens (HLA) typing. Association between fever 5–12 days after MMR (“MMR-associated”) and HLA type was assessed using logistic regression. We compared 42-day post-vaccination geometric mean titers (GMT) to measles between children who did and did not have fever using a t-test. We enrolled 86 children and performed HLA typing on 82; 13 (15.1%) had MMR-associated fever. Logistic regressions identified associations between MMR-associated fever and HLA Class I loci A-29:02 (P = .036), B-57:01 (P = .018), C-06:02 (P = .006), C-14:02 (P = .022), and Class II loci DRB1-15 (P = .045). However, Bonferroni's adjustment for multiple comparisons suggests that these associations could have been due to chance. Ninety-eight percent of children had protective antibody titers to measles; however, GMT was higher among those with fever compared with children without fever (P = .006). Fever after the measles vaccine correlated with genetic factors and higher immune response. This study suggests a possible genetic susceptibility to MMR-associated fever.

KEYWORDS:

• MMR
• MMRV
• vaccine
• genetic factors
• fever
• antibody
• titers

Acknowledgments

We would like to thank Charlie Chao, MA, CCRP for assistance with sample preparation, shipping, and data management.

Disclosure of potential conflicts of interest

NPK report research support from GlaxoSmithKline for the Phase 3 clinical trial from which the patients in the study were recruited. The measles vaccines which are the focus of this study were provided by GlaxoSmithKline as part of this clinical trial. NPK has received research grants from GlaxoSmithKline, Sanofi Pasteur, Merck, Pfizer, and Protein Science. All other authors have no conflicts of interest relevant to this article to disclose.

All authors attest they meet the ICMJE criteria for authorship.

Supplementary data

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Additional information

Funding

This work was supported by the U.S. Department of Health and Human Services, under a cooperative agreement with the National Vaccine Program Office, to NPK. OZ was funded in part by grant 1K01AI139275-01 from the National Institute of Allergy and Infectious Diseases.