Vaccine Trials

An effective WNV equine vaccine has been FDA approved to protect horses, but there is no approved vaccine for humans.  Many researchers are working to develop a human vaccine. The National Institute of Allergy and Infectious Diseases (NIAID) is supporting the development of several West Nile virus vaccine approaches, including:chimeric vaccine, naked DNA vaccine and viral protein cocktails

• Chimeric vaccines are constructed by splicing a specific set of genes from virus (B) into the genetic code of a live attenuated virus (A). The resulting hybrid virus (BA) expresses enough virus (B) to stimulate an immune response while retaining the diminished reproductive and pathogenic characteristics of virus (A).
  
  Equine WNV vaccines are produced this way. Genes of WNV are spliced into the genome of attenuated yellow fever or dengue fever viruses. One method of creating an attenuated virus, is to grow successive generations of the virus in cooler and cooler temperatures, until it mutates to reproduce most efficiently in a cold environment. When introduced into animals, our body temperature limits the virus's ability to reproduce faster than our immune system can control. Hopefully, human testing will soon demonstrate that these chimeric vaccines are as safe and effective in humans as there are in horses.
  
  
• DNA vaccines are composed of strands of gene sequences (plasmids) which are injected into the patient. The DNA is taken up by cells and translated into proteins which are expressed by patient cells. The patient's immune system recognizes these proteins as foreign and mounts a protective response against the proteins, which are components of the virus. Such WNV DNA vaccines have proved to be effective in mice. More testing is necessary before human vaccines will be approved.
  
  
• Viral protein cocktail vaccines can be created by selecting viral genes that code for specific viral proteins. These genes are then spliced into the genome of easily grown organisms such as E. coli or yeasts. These (recombinant) organisms produce large quantities of the selected viral proteins. The proteins are then seperated from the organisms, purified and diluted, to produce the vaccine. These purified proteins are introduced into the recipeint and the recipient mounts an immune response to the foreign proteins.
  
  
• Anti-mosquito-saliva vaccine (AGS-v vaccine). Unlike other vaccines targeting specific mosquito-borne diseases, the AGS-v candidate is designed to trigger an immune response to mosquito saliva rather than to a specific virus or parasite carried by mosquitoes. The test vaccine contains four synthetic proteins from mosquito salivary glands. The proteins are designed to induce antibodies in a vaccinated individual and to cause a modified allergic response that can prevent infection when a person is bitten by a disease-carrying mosquito.
  
  An NIH randomized, double-blind, Phase I study (ClinicalTrials.gov Identifier: NCT03055000) will evaluate the safety and immunogenicity of AGS-v is expected to end in Dec. of 2019. The study will measure base-line and post-vaccination host immune responses to uninfected Aedes aegypti mosquito feeding, again measuring AGS-v specific total immunoglobulin, primarily IgG1, IgG3, and IgM. It will also look at the vaccine effect on the mosquitoes, their feeding habits and fecundity after feeding on the blood of vaccinated individuals. Time permitting, the researchers aim to investigate interactions between PBMCs/serum from vaccinated participants and mosquito saliva-coated Zika viruses in-vitro (NIAID).

Reference

National Institute of Allergy and Infectious Desease. News & Events. Newsroom. News Releases. NIH Begins Study of Vaccine to Protect Against Mosquito-Borne Diseases. Retrieved 11/6/2017

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