Evaluation of Antibody Responses Elicited by Zika Vaccination in Flavivirus-Naive and -Experienced Individuals

Grants and Contracts Details

Description

Zika virus (ZIKV), a member of the flavivirus genus, recently precipitated widespread cases of 1 neurological pathology and congenital neurologic defects. In response, a multilateral coalition of 2 investigators began developing vaccine candidates that elicited potent ZIKV-neutralizing antibodies, 3 which correlated with protection from ZIKV challenge in animal models (reviewed in1-4). Despite these 4 advances, it remains unclear how the ZIKV immunization response is shaped in humans with and 5 without prior flavivirus exposure, such as dengue virus (DENV), Japanese encephalitis (JEV), or yellow 6 fever virus (YFV), which have significant epidemiologic overlap with ZIKV. Our long-term goal is to 7 understand the underlying mechanisms of humoral immunity generated by flavivirus vaccination, which 8 can provide long-term protection in flavivirus-naïve and/or flavivirus-experienced populations. Such 9 information would guide vaccination strategies in flavivirus-endemic areas or among flavivirus-naïve 10 populations traveling to endemic areas. The overall objective of the proposed research is to 11 evaluate the specificity and function of the B cell antibody repertoire elicited by immunization 12 with a ZIKV vaccine candidate in both flavivirus-naïve and flavivirus-experienced individuals. 13 Our central hypothesis is that the specificity and function of the antibody repertoire will be determined 14 by B cell memory recall responses to cross-reactive epitopes from prior flavivirus-exposure whereas 15 flavivirus-naïve individuals will develop primary B cell responses against ZIKV-specific epitopes. We 16 recently reported that a single-dose immunization of a ZIKV purified inactivated vaccine (ZPIV)5-8 in a 17 dengue (DENV)-experienced individual elicited potent cross-neutralizing antibodies to both ZIKV and 18 DENV9. These data demonstrate that ZPIV immunization in a DENV-experienced individual can boost 19 pre-existing flavivirus immunity and elicit protective responses against ZIKV and DENV. A goal of this 20 proposal is to expand on these findings to determine the prevalence of B cell antibody repertoire elicited 21 in a broader set of flavivirus-experienced individuals compared to flavivirus-naïve individuals following 22 ZIKV vaccination. 23 24
StatusActive
Effective start/end date4/1/243/31/27

Funding

  • Henry M Jackson Foundation for the Advancement of Military Medicine Incorporated: $107,936.00

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