In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 15, No. 4 ( 2021-4-1), p. e0009308-
Abstract:
Mayaro virus (MAYV) is an alphavirus endemic to South and Central America associated with sporadic outbreaks in humans. MAYV infection causes severe joint and muscle pain that can persist for weeks to months. Currently, there are no approved vaccines or therapeutics to prevent MAYV infection or treat the debilitating musculoskeletal inflammatory disease. In the current study, a prophylactic MAYV vaccine expressing the complete viral structural polyprotein was developed based on a non-replicating human adenovirus V (AdV) platform. Vaccination with AdV-MAYV elicited potent neutralizing antibodies that protected WT mice against MAYV challenge by preventing viremia, reducing viral dissemination to tissues and mitigating viral disease. The vaccine also prevented viral-mediated demise in IFN⍺R1 -/- mice. Passive transfer of immune serum from vaccinated animals similarly prevented infection and disease in WT mice as well as virus-induced demise of IFN⍺R1 -/- mice, indicating that antiviral antibodies are protective. Immunization with AdV-MAYV also generated cross-neutralizing antibodies against two related arthritogenic alphaviruses–chikungunya and Una viruses. These cross-neutralizing antibodies were protective against lethal infection in IFN⍺R1 -/- mice following challenge with these heterotypic alphaviruses. These results indicate AdV-MAYV elicits protective immune responses with substantial cross-reactivity and protective efficacy against other arthritogenic alphaviruses. Our findings also highlight the potential for development of a multi-virus targeting vaccine against alphaviruses with endemic and epidemic potential in the Americas.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0009308
DOI:
10.1371/journal.pntd.0009308.g001
DOI:
10.1371/journal.pntd.0009308.g002
DOI:
10.1371/journal.pntd.0009308.g003
DOI:
10.1371/journal.pntd.0009308.g004
DOI:
10.1371/journal.pntd.0009308.g005
DOI:
10.1371/journal.pntd.0009308.g006
DOI:
10.1371/journal.pntd.0009308.g007
DOI:
10.1371/journal.pntd.0009308.g008
DOI:
10.1371/journal.pntd.0009308.g009
DOI:
10.1371/journal.pntd.0009308.g010
DOI:
10.1371/journal.pntd.0009308.s001
DOI:
10.1371/journal.pntd.0009308.s002
DOI:
10.1371/journal.pntd.0009308.s003
DOI:
10.1371/journal.pntd.0009308.s004
DOI:
10.1371/journal.pntd.0009308.r001
DOI:
10.1371/journal.pntd.0009308.r002
DOI:
10.1371/journal.pntd.0009308.r003
DOI:
10.1371/journal.pntd.0009308.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2429704-5
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