Investigation of sarbecovirus exposure patterns and development of pan-SARS-CoV-2 neutralizing antibody responses in high-risk cohorts in Myanmar

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Principal Investigator: Tierra Smiley Evans
Organization: UNIVERSITY OF CALIFORNIA AT DAVIS
Fiscal Year: 2023
Award: $204,874
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY
Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern pose a
global challenge to the effectiveness of existing and future vaccines. This project will address questions
surrounding the immunological response to different sarbecovirus exposure patterns with implications for
vaccine development by conducting longitudinal repeated surveillance of unique human populations,
previously determined to be highly exposed to a diversity of SARS-CoV-2-related coronaviruses in
Myanmar. There is a timely opportunity to follow these communities, particularly immediately following
SARS-CoV-2 infection and/or vaccination to understand which previous sarbecovirus exposure patterns
expand the likelihood of development of pan-sarbecovirus neutralizing antibodies. We will evaluate the
impact of diverse patterns of natural and vaccination-based sarbecovirus exposure on development of pan-
sarbecovirus neutralizing antibodies by following three specific human cohorts: (1) elephant loggers
engaged in bushmeat hunting (including bats and pangolins) during the process of active deforestation of
Myanmar’s remaining teak forests, (2) bat guano harvesting communities surrounding HpaAn cave systems
in Kayin State and (3) a previously uninvestigated population engaged in religious activities within the Karst
cave systems in the Northern Dawna range. Waxing and waning of specific antibody responses will be
followed over time through use of pre-pandemic archived specimens from these populations and repeated
prospective sampling. We will utilize a novel Luminex bead-based multi-plex sarbecovirus assay, capable
of simultaneously detecting neutralizing antibodies against 21 different hACE2-binding sarbecoviruses.
Exposure patterns to specific sarbecoviruses will be identified and viral characteristics evaluated for their
contribution to the likelihood of developing pan-sarbecovirus antibody responses, including viral genetic and
functional phenotypic similarity and host plasticity (breadth of host species a virus is known to infect).
Patterns of prior natural sarbecovirus exposure coupled with natural SARS-COV-2 infection and / or
vaccination will then be evaluated for contributions to broadly reactive antibody responses. Data generated
through this project will inform on potential cross sarbecovirus clade vaccination strategies that could protect
against both known and future emerging SARS-CoV-2 variants. We will also conduct an in-depth
investigation of behavioral risk factors contributing to zoonotic sarbecovirus spillover that will aid in
mitigation strategies in this critically important ecological region for coronavirus emergence.

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