Antibody effector analysis of prime versus prime-boost immunizations with a recombinant measles-vectored chikungunya virus vaccine
Roland Tschismarov, Raphaël M. Zellweger, Min Jie Koh, Yan Shan Leong, Jenny G. Low, Eng Eong Ooi, Christian W. Mandl, Katrin Ramsauer, Ruklanthi de Alwis
Roland Tschismarov, Raphaël M. Zellweger, Min Jie Koh, Yan Shan Leong, Jenny G. Low, Eng Eong Ooi, Christian W. Mandl, Katrin Ramsauer, Ruklanthi de Alwis
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Research Article Immunology Vaccines

Antibody effector analysis of prime versus prime-boost immunizations with a recombinant measles-vectored chikungunya virus vaccine

Abstract

Chikungunya is a mosquito-borne disease that causes periodic but explosive epidemics of acute disease throughout the tropical world. Vaccine development against chikungunya virus (CHIKV) has been hampered by an inability to conduct efficacy trials due to the unpredictability of CHIKV outbreaks. Therefore, immune correlates are being explored to gain inference into vaccine-induced protection. This study is an in-depth serological characterization of Fab- and Fc-mediated antibody responses in selected phase II clinical trial participants following immunization with the recombinant measles-vectored CHIKV vaccine, MV-CHIK. Antibody comparisons were conducted between participants who received prime and those who received prime-boost vaccine regimens. MV-CHIK vaccination elicited potent Fab-mediated antibody responses (such as CHIKV-specific IgG, neutralization, and avidity), including dominant IgG3 responses, which translated into strong antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. At 1 month, prime-boost immunization led to significantly greater responses in every measured Fab and Fc antibody parameter. Interestingly, prime-boost-elicited antibodies decreased rapidly over time, until at 6 months both vaccine regimens displayed similar antibody profiles. Nonetheless, antibody avidity and antibody-dependent cellular phagocytosis remained significantly greater following boost immunization. Our observations suggest that a prime-boost administration of MV-CHIK will be more appropriate for CHIKV-endemic regions, while a prime-only regimen may be sufficient for travel purposes or outbreak situations.

Authors

Roland Tschismarov, Raphaël M. Zellweger, Min Jie Koh, Yan Shan Leong, Jenny G. Low, Eng Eong Ooi, Christian W. Mandl, Katrin Ramsauer, Ruklanthi de Alwis

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Figure 1

Study design and characterization of the CHIK-specific IgG response elicited by MV-CHIK prime and prime-boost vaccination strategies.

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Study design and characterization of the CHIK-specific IgG response elic...
(A) Participants were vaccinated with either MV-CHIK prime at day 0 (P only) or prime (at month –1) and boost (at day 0) (P+B), and serum antibody responses were compared at 1 and 6 months after vaccination. MV-vaccinated groups served as controls. (B–F) Total IgG binding to CHIKV virus was measured using ELISA and compared (B) between groups and (C) at 1 and 6 months for paired MV-CHIK–vaccinated samples. (D) Fold change in IgG (mean ± 95% CI) in response to CHIKV virus was compared between MV-CHIK P only and P+B. IgG binding to 2 CHIK surface glycoproteins, E1 and E2, was measured using Luminex immunoassay and compared between groups at (E) 1 month and (F) 6 months after vaccination. (G) Distribution of the CHIK antigens targeted by the antibody response was estimated by the ratio of E2-specific to E1-specific IgG (mean ± 95% CI) and compared between prime and prime-boost MV-CHIK vaccinations. IgG responses between groups were compared using Mann-Whitney U test, while paired analysis between groups at 1 and 6 months was conducted using paired Wilcoxon signed-rank test (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001).