Distinct Humoral Response Development to Measles Virus across Vaccine Platforms

Abstract Background Different measles vaccine platforms protect against clinical disease, but characteristics of the resulting humoral responses remain incompletely defined. Methods In this study, a phage-display immunoprecipitation sequencing technology, VirScan, was employed to evaluate measles viral epitope coverage by antibodies following wild-type (WT) measles virus (MeV) infection of rhesus macaques, or vaccination with a live-attenuated MeV vaccine (LAMV), the triple measles mumps rubella vaccine (MMR) or a novel recombinant MeV hemagglutinin protein-based vaccine (rMeVH). Vaccinated animals were also challenged with WT MeV to measure antibody epitope reactivity during a recall. Results The results demonstrate that WT MeV infection elicited a broader epitope reactivity profile than LAMV-containing vaccines. Also, rMeVH vaccination not only resulted in a narrow H-protein specific antibody profile, but epitopes recognized were distinct from LAMV-vaccinated or WT-challenged animals. All vaccine groups expanded the breadth of MeV-specific antibody repertoires following WT MeV challenge. In addition, MeV-specific VarScore, a measure of overall antigen-binding, was positively correlated with IgG titer assessed by ELISA, as well as antibody avidity, and neutralizing titers. Conclusions The results demonstrate the distinct effects of vaccination platforms on the breadth and fine specificity of anti-measles induced humoral responses, and the utility of VirScan for comprehensively assessing antibody epitope targets.