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Distinct Humoral Response Development to Measles Virus across Vaccine Platforms
Andy K P Chan1,2, Jacqueline K Brockhurst1,3, Liting Liu1
1W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
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.
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