Non-replicating adenovirus based mayaro virus vaccine elicits protective immune responses and cross protects against other alphaviruses

John M. Powers, Nicole N. Haese, Michael Denton, Takeshi Ando, Craig Kreklywich, Kiley Bonin, Cassilyn E. Streblow, Nicholas Kreklywich, Patricia Smith, Rebecca Broeckel, Victor Defilippis, Thomas E. Morrison, Mark T. Heise, Daniel N. Streblow

Research output: Contribution to journalArticlepeer-review

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 IFNαR1-/- mice. Passive transfer of immune serum from vaccinated animals similarly prevented infection and disease in WT mice as well as virus-induced demise of IFNαR1-/- 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 IFNαR1-/- 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.

Original languageEnglish (US)
Article numbere0009308
JournalPLoS neglected tropical diseases
Volume15
Issue number4
DOIs
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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