Engineered DNA Vaccine Protects Against Emerging Mayaro Virus Infection
PHILADELPHIA — (Feb. 7, 2019) — A novel, synthetic DNA vaccine developed at The Wistar Institute induces protective immunity against Mayaro virus (MAYV), a mosquito-borne infection endemic to South America, that has the potential to become a global emerging viral threat. Study results were published in PLOS Neglected Tropical Diseases.
Since its discovery in 1954, MAYV infections have been confined to the heavily forested areas of Trinidad and Tobago and the neighboring regions of South America. However, a reported case of MAYV infection in Haiti in 2015 and laboratory evidence suggest that multiple mosquito species can transmit MAYV, highlighting the potential for further uncontrolled expansion of MAYV into tropical regions of the Caribbean and Central and South America.
“Although MAYV was discovered a long time ago and can cause severe health complications, it remains a neglected disease and is understudied,” said Kar Muthumani, Ph.D., director of the Laboratory of Emerging Infectious Diseases at The Wistar Institute and assistant professor in Wistar’s Vaccine & Immunotherapy Center. “The potential for this virus to spread beyond its historical geographic range, as Zika virus did a few years ago, makes the creation of an effective immunization strategy even more pressing.”
Similar to infections caused by dengue or chikungunya viruses, MAYV infection causes fever, rash, headache, nausea, and vomiting for prolonged periods in many people and can lead to persistent and debilitating muscle and joint pain in some patients. There are no approved treatments or preventative medicines for Mayaro fever.
In the new study, Muthumani and colleagues created a novel synthetic DNA vaccine targeting MAYV envelope (E) protein isolated from the major circulating strains of MAYV (“scMAYV-E”). The vaccine’s unique design accounts for the natural genetic variability of this major viral surface antigen, and it was optimized to improve its expression in vivo. The scMAYV-E DNA vaccine was administered by intramuscular injection followed by electroporation, pulses of electricity designed to make cells more permeable to foreign DNA and enhance vaccine uptake, which allows for dose-sparing.
Immunization with scMAYV-E induced potent protective and MAYV-specific immune responses in mice, including both MAYV infection-neutralizing antibodies as well as cellular responses to multiple regions of MAYV-E. Importantly, the scMAYV-E vaccine provided complete protection from death and clinical signs of infection in a MAYV-challenge mouse model.
“The robust immunogenicity of the scMAYV-E vaccine demonstrated here supports the need for further testing of this vaccine as a viable means to halt the spread of this virus and protect individuals at risk from MAYV disease,” added Muthumani. “DNA vaccines have a remarkable safety record in numerous clinical trials, can be designed and manufactured readily, and can be distributed cost-effectively, making them an important tool for combating emerging infectious diseases like MAYV especially in resource-poor settings, where they often arise.”
Co-authors: Hyeree Choi (first author), Sagar B. Kudchodkar, Emma L. Reuschel, Kanika Asija, Piyush Borole, Michelle Ho, Krzysztof Wojtakand, and David B. Weiner from The Wistar Institute; Charles Reed, Stephanie Ramos, Joseph Kim, and Laurent Humeau from Inovio Pharmaceuticals, Inc.; Nathen E. Bopp, Patricia V. Aguilar, and Scott C. Weaver from University of Texas Medical Branch, Galveston; and Pablo Tebas from University of Pennsylvania.
Work supported by: Inovio Pharmaceuticals, Inc.
Publication information: Protective immunity by an engineered DNA Vaccine for Mayaro Virus, PLOS Neglected Tropical Diseases (2019). Advanced online publication.
The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.