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.
Highlights
Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that circulates in zoonotic cycles in non-human primates, birds, and rodents with occasional spillover into human populations that can lead to urban spread [1]
Mayaro virus is an understudied alphavirus that is currently circulating in tropical environments in South and Central America without an approved vaccine
Mayaro virus is closely related to other arthritogenic alphaviruses with overlapping circulation such as chikungunya and Una viruses, both of which lack clinically approved vaccines
Summary
Mayaro virus (MAYV) is a mosquito-transmitted alphavirus that circulates in zoonotic cycles in non-human primates, birds, and rodents with occasional spillover into human populations that can lead to urban spread [1]. The ability of the virus to infect both Aedes and Culex mosquitos and a wide range of vertebrate hosts potentially permitting both enzootic and urban transmission cycles [2]. Upon returning to urban areas, this can lead to human outbreaks [3]. Human infection with MAYV leads to fever, myalgia, arthralgia, and rash, which are common symptoms of infection with other arthritogenic alphaviruses. Based on similarity to other more prevalent alphaviruses, reduced reporting of MAYV infections could be due to misdiagnosis, most commonly as dengue fever or chikungunya disease [4]
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