Human vaccine for dangerous mosquito-borne viruses shows promise in clinical trial

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A colorised transmission electron micrograph showing a salivary gland that had been extracted from a mosquito, which was infected by the Eastern equine encephalitis (EEE) virus, which has been colorized red and magnified 83,900 times.
A colorised transmission electron micrograph showing a salivary gland that had been extracted from a mosquito, which was infected by the Eastern equine encephalitis (EEE) virus, which has been colorized red and magnified 83,900 times. Image: Fred Murphy and Sylvia Whitfield (CDC Public Health Image Library Image #7057), public domain, via Wikimedia Commons

A human vaccine for eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV), and Venezuelan equine encephalitis virus (VEEV) has been found to be safe, well-tolerated and induced a neutralizing antibody response in volunteers, researchers report.

The vaccine candidate was developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC), part of the National Institutes of Health in the United States.

NIAID also sponsored and funded the clinical trial, conducted at the Emory Vaccine Center’s Hope Clinic, part of Emory University in Atlanta. The study, which describes the results from the Phase 1 clinical trial, appear in The Lancet Infectious Diseases journal.

EEEV, WEEV and VEEV are spread to humans through the bites of infected mosquitoes. Horses are also susceptible to infection, but horses 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 United States that led to 38 confirmed cases and 15 deaths.

Under certain laboratory conditions, the viruses can transmit through the air by aerosol droplets and cause infection in humans and are therefore classified as priority pathogens, potential biological agents that pose a risk to national security and public health.

NIAID director Anthony Fauci and colleagues have highlighted the possible usefulness 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, VRC researchers designed a virus-like particle (VLP) vaccine candidate that uses proteins from the outer shells of the EEE, WEE and VEE viruses to prompt an immune response.

VLPs do not contain the genetic material that the viruses need to replicate inside cells, so VLPs cannot cause infection.

For the Phase 1 clinical trial, 30 healthy adult volunteers ages 18 to 50 years received varying doses of the WEVEE vaccine (6, 30 or 60 micrograms) 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 neutralizing antibody response was observed in participants who received the 30-microgram dose with adjuvant. The authors note that the findings support further clinical evaluation of the vaccine candidate.

NIAID has executed a commercialization license for the advanced development of the WEVEE vaccine candidate to the life sciences company Emergent BioSolutions in Gaithersburg, Maryland.

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 Joint Program Executive Office Chemical, Biological, Radiological and Nuclear Defense.

Vaccines against the pathogens have been available for horses for some years.

Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial. The Lancet Infectious Diseases, 2022; Emily E Coates, Srilatha Edupuganti, Grace L Chen, Myra Happe, Larisa Strom, Alicia Widge, Maria Burgos Florez, Josephine H Cox, Ingelise Gordon, Sarah Plummer, Abidemi Ola, Galina Yamshchikov, Charla Andrews, Sharon Curate-Ingram, Patricia Morgan, Shashi Nagar, Matthew H Collins, Amy Bray, Thuy Nguyen, Judy Stein, Christopher L Case, Florence Kaltovich, Diane Wycuff, C Jason Liang, Kevin Carlton, Sandra Vazquez, John R Mascola, Julie E Ledgerwood, Ellie Butler, Jean Winter, Jianguo Xu, Amy Sherman, Colleen Kelley, Rameses Fredrick, Nadine Rouphael, Varun Phadke, Cynthia Whitney, Alicarmen Alvarez, Renata Dennis, Rebecca Fineman, Pamela Lankford-Turner, Sha Yi, Lilin Lai, Gena Burch, Shanker Gupta, Nina Berkowitz, Cristina Carter, Allison Beck, Brenda Larkin, Stephanie Taylor, Mandy Alger, Jessica Bahorich, Amy Lynch Chamberlain, Ya-chen Chang, Rajoshi Chaudhuri, Jonathan Cooper, Jacob Demirji, Fan Yang, Alissa Fernald, Deepika Gollapudi, Janel Holland-Linn, Lisa Kueltzo, James Lee, Jie Liu, Xun Liu, Rachel Mowery, Sarah O’Connell, Erwin Rosales-Zavala, Jason Sands, Xin Wang, Shaojie Weng, Sara Witter.  DOI: 10.1016/S1473-3099(22)00052-4

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