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Protective immunity by an engineered DNA vaccine for Mayaro virus
Hyeree Choi1, Sagar B Kudchodkar1, Emma L Reuschel1
1Vaccine & Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States of America.
Abstract:
Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.
Insights
A new DNA vaccine, scMAYV-E, shows promise for preventing Mayaro virus (MAYV) infection. This vaccine effectively generated immune responses in mice, protecting them from the dangerous effects of MAYV.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Mayaro virus (MAYV) is an emerging alphavirus causing febrile illness and persistent arthralgias.
- MAYV is spreading to new regions, including the Caribbean, via competent vectors like Aedes mosquitoes.
- Currently, no vaccines or therapeutics exist for Mayaro virus infection.
Purpose of the Study:
- To develop and evaluate a novel DNA vaccine, scMAYV-E, against Mayaro virus.
- To assess the immunogenicity and protective efficacy of the scMAYV-E vaccine in a preclinical model.
Main Methods:
- Development of a DNA vaccine encoding a synthetic consensus Mayaro virus envelope sequence (scMAYV-E).
- In vivo electroporation-enhanced immunization of mice with the scMAYV-E vaccine.
- Assessment of humoral (neutralizing antibodies) and cellular (T-cell) immune responses.
- Evaluation of protection against Mayaro virus challenge in vaccinated mice.
Main Results:
- scMAYV-E vaccination induced potent humoral immune responses, including neutralizing antibodies against Mayaro virus.
- Robust T-cell responses targeting multiple epitopes within the Mayaro virus envelope were observed.
- Vaccinated mice demonstrated significant protection against Mayaro virus-induced morbidity and mortality.
Conclusions:
- The novel DNA vaccine scMAYV-E is immunogenic and elicits protective immunity against Mayaro virus.
- scMAYV-E represents a promising candidate for a Mayaro virus vaccine.
- Further development of this DNA vaccine could address the unmet medical need for Mayaro virus prevention.
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