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Non-replicating adenovirus based Mayaro virus vaccine elicits protective immune responses and cross protects against
John M Powers1,2, Nicole N Haese1, Michael Denton1
1Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
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.
Insights
A novel adenovirus-based vaccine (AdV-MAYV) effectively protects mice against Mayaro virus infection by eliciting neutralizing antibodies. This vaccine also shows cross-protection against related alphaviruses, offering potential for a broad-spectrum vaccine.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Mayaro virus (MAYV) causes severe, persistent musculoskeletal pain and is endemic in the Americas.
- No current vaccines or therapeutics exist for MAYV infection or its associated inflammatory disease.
Purpose of the Study:
- To develop and evaluate a prophylactic vaccine against Mayaro virus (MAYV) using a non-replicating human adenovirus V (AdV) platform.
- To assess the vaccine's ability to induce protective immunity and cross-reactivity against related alphaviruses.
Main Methods:
- A recombinant adenovirus vector (AdV-MAYV) expressing the MAYV structural polyprotein was constructed.
- Vaccine efficacy was tested in wild-type (WT) and interferon-alpha/beta receptor knockout (IFN⍺R1-/-) mice challenged with MAYV.
- Passive transfer of immune serum was used to confirm antibody-mediated protection.
- Cross-neutralization and protection against chikungunya and Una viruses were evaluated.
Main Results:
- AdV-MAYV vaccination induced potent neutralizing antibodies and protected WT mice from MAYV challenge, preventing viremia and reducing disease.
- The vaccine conferred protection against lethal MAYV challenge in IFN⍺R1-/- mice.
- Immune serum passively transferred protection in both WT and IFN⍺R1-/- mice.
- AdV-MAYV immunization generated cross-neutralizing antibodies protective against chikungunya and Una viruses in IFN⍺R1-/- mice.
Conclusions:
- The AdV-MAYV vaccine elicits protective immune responses against Mayaro virus.
- The vaccine demonstrates significant cross-reactivity and protective efficacy against other arthritogenic alphaviruses.
- This AdV-MAYV vaccine platform holds potential for a multi-virus vaccine targeting endemic and epidemic alphaviruses in the Americas.
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