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
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Status | Active |
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Effective start/end date | 4/1/24 → 3/31/27 |
Funding
- Henry M Jackson Foundation for the Advancement of Military Medicine Incorporated: $107,936.00
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