Background: Complex patterns of cross-reactivity exist between flaviviruses, yet there is no precise understanding of how sequential exposures due to flavivirus infections or vaccinations impact subsequent antibody responses.
Methods: We investigated whether B cell priming from Japanese encephalitis virus (JEV) or yellow fever virus (YFV) vaccination impacted binding and functional antibody responses to flaviviruses following vaccination with a Zika virus (ZIKV) purified inactivated virus (ZPIV) vaccine. Binding antibody responses and Fc gamma receptor engagement against 23 flavivirus antigens were characterized along with neutralization titres and Fc effector responses in 75 participants at six time points.
Findings: We found no evidence that priming with JEV or YFV vaccines improved the magnitude of ZPIV induced antibody responses to ZIKV. Binding antibodies and Fc gamma receptor engagement to ZIKV antigens did not differ significantly across groups, while antibody-dependent cellular phagocytosis (ADCP) and neutralizing responses were higher in the naïve group than in the JEV and YFV primed groups following the second ZPIV immunization (p ≤ 0.02). After a third dose of ZPIV, ADCP responses remained higher in the naïve group than in the primed groups. However, priming affected the quality of the response following ZPIV vaccination, as primed individuals recognized a broader array of flavivirus antigens than individuals in the naïve group.
Interpretation: While a priming vaccination to either JEV or YFV did not boost ZIKV-specific responses upon ZIKV vaccination, the qualitatively different responses elicited in the primed groups highlight the complexity in the cross-reactive antibody responses to flaviviruses.
Funding: This work was supported by a cooperative agreement between The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of the Army [W81XWH-18-2-0040]. The work was also funded in part by the National Institute of Allergy and Infectious Diseases (NIAID) R01AI155983 to SJK and KM.
Competing Interests: Declaration of interests Kayvon Modjarrad is an employee of Pfizer. Rafael De La Barrera is one of the inventors for the WO2017210215A1 Patent: Zika virus vaccine and methods of production. All other authors declare that they have no competing interests. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the Department of Defense, or the Department of Health and Human Services.
(Copyright © 2023 Henry M Jackson Foundation for the Advancement of Military Medicine, Inc. Published by Elsevier B.V. All rights reserved.)