Genome-Wide Association Mapping of the Antibody Response to Diphtheria, Tetanus and Acellular Pertussis Vaccine in Mice

• Published in: The Journal of infectious diseases Vol. 215; no. 3; pp. 466 - 474
• Main Authors: Mosley, Yung-Yi C., Radder, Josiah E., Berndt, Annerose, HogenEsch, Harm
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.02.2017
• Subjects: Animals; Diphtheria-Tetanus-Pertussis Vaccine - immunology; Enzyme-Linked Immunosorbent Assay; Female; Genetic Variation; Genome-Wide Association Study; Immunogenicity, Vaccine - genetics; Immunoglobulin G - immunology; Longevity - genetics; Mice; Mice, Inbred Strains; PATHOGENESIS AND HOST RESPONSE; antibody longevity; antibody titer; genetics; GWAS; antibody avidity; mouse model; pertussis; vaccination; DTaP
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiw587

The objective of the current study was to investigate the genetics of antibody responses to an acellular pertussis vaccine by a genome-wide association study in mice. Female mice of 28 inbred strains received this vaccine at 6, 8, and 12 weeks of age. The antibody titer and avidity of immunoglobulin (Ig) G specific for diphtheria toxin, pertussis toxin, filamentous hemagglutinin and pertactin were measured at 14 and 24 weeks of age. The magnitude, longevity and avidity of IgG differed significantly among mouse strains. There was significant correlation between antigen-specific IgGs for longevity but not for magnitude and avidity. Association mapping and analysis with PolyPhen software identified 6 genetic markers associated with longevity for all 4 antigens, although the expression levels of these genes did not correlate with longevity phenotype. This study provides novel insights into the genetic basis and potential candidate genes for differences in the IgG responses to vaccination.