Annual and Interim Progress Report Summaries
Principal Investigator: Chris Parks
Project: A Research Consortium Dedicated to the Invention, Systematic Evaluation and Development of Novel AIDS Vaccine Candidates that Elicit Potent, Durable and Protective T Cell Responses
Submitted September 5, 2012
Many important vaccines are based on live but weakened viruses such as the vaccines used to prevent measles, mumps, and polio. These vaccines are effective because immunization causes a mild or unapparent viral infection that establishes long-term immunity that protects against later exposure to pathogenic virus. Unfortunately, this approach cannot be used readily to develop an AIDS vaccine because it will be problematic to generate a weakened HIV strain considered safe to use for immunization. Therefore, our objective is to use unrelated live viruses as vectors to deliver an AIDS vaccine.
Our CAVD Team has developed and evaluated a variety of novel viral vector technologies and narrowed our focus on three candidates: cytomegalovirus (CMV), canine distemper virus (CDV) and vesicular stomatitis virus (VSV). These viruses each have unique biological characteristics expected to be important for stimulating immunity that can control or inactivate the AIDS virus.
The vectors are being evaluated rigorously by making and testing experimental vaccines against simian immunodeficiency virus (SIV). Earlier studies conducted with the CMV-SIV vaccine showed that about 50% of vaccinated male rhesus macaques rapidly and strongly suppressed SIV infection following rectal exposure with a highly pathogenic SIV strain. Most recently, a large study also demonstrated protection from vaginal infection in 50% of vaccinated females. Because of these exceptional findings, the CMV vector has advanced into a new CAVD program devoted to developing a HIV vaccine candidate for use in clinical studies.
Prototype SIV vaccines based on VSV and CDV have been tested in a small number of macaques. Importantly, both vaccines induced antibodies against SIV proteins including Env, which is present on the surface of virus particles and is responsible for initiating infection. Further testing is underway to determine if the immunity elicited by VSV-SIV and CDV-SIV vaccines protect animals from SIV infection.