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NIH grant 1R01AI200941-01: Mechanism of cross-reaction and cross-protection for Mayaro virus elicited by chikungunya vaccine
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: William Marciel De Souza. Award: $802421.
Start: 2026-07-24T00:00:00.
Project Summary/Abstract:
Arthritogenic alphaviruses are mosquito-borne viruses that can cause acute and chronic polyarthralgia in
humans, impacting public health and economies worldwide. Chikungunya virus (CHIKV) is the most widespread
arthritogenic alphavirus, causing 16.9 million annual cases, and nearly 2.8 billion people live in areas at risk for
CHIKV infection. In Latin America and the Caribbean, CHIKV geographically co-circulates with Mayaro virus
(MAYV), another arthritogenic alphavirus that is an emerging viral threat. At present, no vaccines or specific
therapeutics are available to treat or prevent MAYV infection. Vimkunya is a virus-like particle (VLP) vaccine
against chikungunya disease approved in the United States of America in February 2025. The protection by
Vimkunya likely relies on antibodies that neutralize CHIKV, and it is hypothesized to provide cross-protection
against MAYV infection. Currently, three key questions about Vimkunya and cross-protection against MAYV
infection need to be addressed: 1) Do neutralizing antibodies elicited by Vimkunya vaccination prevent disease
caused by MAYV infection? 2) Do Vimkunya-elicited antibodies protect against MAYV infection through effector
functions? 3) Does Vimkunya vaccination elicit cross-reactive T and B cell responses that contribute to protection
against Mayaro disease? To address these fundamental unknowns, we will utilize human and rhesus macaque
models to investigate the immune mechanisms of Vimkunya-induced cross-reactivity and cross-protection
against MAYV infection. Aim 1 will use longitudinal blood sampling of humans vaccinated with Vimkunya,
coupled with systems serology, flow cytometry, and single-cell genomics (scRNA-seq) methods to define the
potential mechanisms of cross-reactivity of antibody, B cell, and T cell responses for MAYV. This approach will
determine the mechanisms of cross-reactivity against MAYV elicited by Vimkunya vaccination in humans. Aim 2
will employ a rhesus macaque model that recapitulates Mayaro disease in humans to investigate mechanisms
of Vimkunya-mediated cross-protection for Mayaro disease. We will immunize rhesus macaques with Vimkunya
and collect blood, lymph nodes, and bone marrow cells at baseline and multiple weeks post-vaccination.
Subsequently, we will perform experimental MAYV infection in both the previously immunized and unimmunized
rhesus macaques, coupled with passive antibody transfer and targeted lymphocyte depletion approaches. Then,
we will apply immunological and genomic methods to examine the role of humoral and cellular responses in
cross-protection in an experimental model that recapitulates Mayaro disease as described in humans. This aim
will define the mechanisms of cross-protection against Mayaro disease generated by Vimkunya immunization.
Overall, the long-term goal of this project is to elucidate the immunological mechanisms of Vimkunya-mediated
cross-reaction and cross-protection against MAYV. The knowledge gained in this study will inform future
Vimkunya immunization programs within CHIKV and MAYV co-endemic regions and may contribute to mitigating
the emergence of MAYV in urban settings.document fetched 2026-08-02 08:24