A Novel Live-Attenuated Vaccine Candidate for Mayaro Fever

Abstract

Mayaro virus (MAYV) is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

Author Summary

Mayaro virus (MAYV) is a mosquito-borne alphavirus that causes severe and sometimes chronic arthralgia in persons in South America, where it circulates in forest habitats. It is widely neglected because it is typically mistaken for dengue due to the overlap in the clinical signs and symptoms, and the lack of laboratory diagnostics in most endemic locations. Furthermore, MAYV has the potential to initiate an urban transmission cycle like that of dengue, which could result in a dramatic increase in human exposure. Because there is no effective vaccine or specific treatment, we developed a candidate vaccine to protect against MAYV infection. We used an attenuation approach based on the elimination of the MAYV subgenomic promoter and insertion of a picornavirus internal ribosome entry site to mediate translation of the structural proteins. This vaccine was well attenuated in mouse models, highly immunogenic, and protected against fatal MAYV infection. Our results indicate that this MAYV strain is promising for further development as a potential human vaccine.