Annual and Interim Progress Report Summaries

Principal Investigator: Christopher Parks

Project: CDV and VSV Viral Vectors

Submitted September 5, 2012

Vaccines based on weakened live viruses have been used to control many important infectious diseases such as smallpox, measles, mumps, rubella, and polio. In experimental settings, this live virus vaccine strategy also has been used to protect rhesus macaques from disease caused by simian immunodeficiency virus (SIV) infection. Although these positive results with experimental live SIV vaccines are very encouraging, using this approach to develop an AIDS vaccine currently is impractical because of the potential risks associated with immunizing people with a live strain of HIV. Consequently, to apply the promising live viral vaccine approach to development of an HIV vaccine, we are modifying two unrelated viruses to make them mimic important elements of the AIDS virus. We have investigated canine distemper virus (CDV) as a vector for delivering AIDS vaccine primarily because it infects a number of the same tissues naturally targeted by HIV. Modifying a CDV strain found in live canine vaccines, we have made vectors that can be administered to rhesus macaques that induce immune responses specific for SIV without causing adverse reactions. We also are working with vesicular stomatitis virus (VSV) because it can be modified to physically resemble an SIV or HIV particle providing an accurate target for inducing immunity. VSV naturally infects livestock but can infect people in close contact with infected animals generally causing an infection that is undetected or produces mild respiratory symptoms. An experimental VSV-SIV vaccine vector has been developed that induces macaques to produce antibodies against proteins found on the SIV surface. We continue to test and improve the CDV-SIV and VSV-SIV vaccine prototypes, and are now advancing development of analogous HIV vaccine candidates.