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WEVEE vaccine shows promise against trio of rare but deadly viruses

Phase I trial data suggests that a vaccine targeting three mosquito-borne encephalitis viruses is safe and can elicit an immune response.

Close up of an Aedes Aegypti Mosquito on human skin - idea of mosquito-borne viruses

A vaccine candidate under development for protection against three mosquito-borne viruses – eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV) and Venezuelan equine encephalitis virus (VEEV) – was found to be safe, well-tolerated and induce a neutralising antibody response in adult volunteers in a Phase I trial.

EEEV, WEEV and VEEV are spread to humans through the bites of infected mosquitoes. Horses are also susceptible to infection, but cannot transmit the viruses directly to humans. Infections in humans are rare but can lead to flu-like symptoms and, in some cases, severe neurological damage or death. The viruses have caused recurrent small outbreaks in North, Central and South America, including an EEEV outbreak in 2019 in the northeastern US that led to 38 confirmed cases and 15 deaths.

Under certain laboratory conditions, these three viruses can be transmitted through the air by aerosol droplets, causing human disease, and are therefore classified as priority pathogens; potential biological agents that pose a risk to national security and public health.

US National Institute of Allergy and Infectious Diseases (NIAID) researchers have previously highlighted the possible utility of a vaccine for EEEV for people at high occupational risk of contracting the disease, including members of the military and laboratory workers. 

Building on their successful development of a vaccine for chikungunya virus, NIAID Vaccine Research Center (VRC) researchers designed a virus-like particle (VLP) vaccine candidate (which they abbreviated to WEVEE) that uses proteins from the outer shells of the EEEV, WEEV and VEEV to prompt an immune response. VLPs do not contain the genetic material that the viruses need to replicate inside cells, therefore they cannot cause infection.

In the Phase I study, 30 healthy adult volunteers aged 18 to 50 years received varying doses of the WEVEE vaccine (6µg, 30µg or 60µg) by intramuscular injection. Participants then returned to receive the same dose as a boost eight weeks later. Some participants also received a formulation of the experimental vaccine that contained an alum adjuvant, added to increase immune responses. Investigators report that the vaccine was safe, well-tolerated and induced durable immune responses against all three viruses. The highest neutralising antibody response was observed in participants who received the 30µg dose with adjuvant.

The authors concluded that “the favourable safety profile and neutralising antibody responses, along with pressing public health need, support further evaluation of the WEVEE VLP vaccine in advanced-phase clinical trials.”

The vaccine candidate was developed by scientists at the NIAID VRC, part of the US National Institutes of Health (NIH). The advanced development of the WEVEE vaccine candidate has been commercially licenced to Emergent Biosolutions.

NIAID sponsored and funded the Phase I clinical trial, which was conducted at the Emory Vaccine Center’s Hope Clinic, part of Emory University in Atlanta, US. Funding for manufacturing of WEVEE clinical trial material and pre-clinical studies was funded in part by an Interagency Agreement between NIAID and the US Department of Defense (DOD) Joint Program Executive Office Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND). 

The results were published in The Lancet Infectious Diseases.