April 24 , 2006
Robinson AIDS vaccine progresses in clinical trials
BY Holly Korschun
A new human clinical trial will begin this month at several sites around the country, testing both components of an HIV/AIDS vaccine developed by a team of researchers at the Yerkes National Primate Research Center, GeoVax Inc., and the Emory Vaccine Center, along with colleagues at the National Institutes of Health (NIH) and the CDC.
The vaccine uses a two-part DNA prime-boost strategy developed by a scientific team led by Harriet Robinson, chief of microbiology and immunology at Yerkes, a faculty member in the vaccine center, and chief of the GeoVax’s scientific advisory board.
The vaccine includes two inoculations of a DNA vaccine that primes the immune system to recognize HIV and two doses of a subsequent booster vaccine based on a recombinant MVA (modified vaccinia ankara) poxvirus. The vaccine produces the three major proteins expressed by HIV and is expected to induce the immune system to respond to these distinguishing features of HIV should the actual virus appear. Neither component of the vaccine incorporates the complete, intact HIV virus.
As reported in Nature Medicine in 1999 and in Science in 2001, a prototype of this vaccine was successful in containing a challenge virus and preventing progression to AIDS in nonhuman primates.
The vaccine technology was licensed to GeoVax, a company founded by Robinson, GeoVax President/CEO Don Hildebrand, Emory and the vaccine center to further develop, manufacture, test and evaluate the vaccine.
In 2003, a prototype DNA vaccine was tested in a group of HIV-negative volunteers to evaluate safety. This Phase I human trial was conducted through the national HIV Vaccine Trials Network (HVTN). Based on these successful studies, the U.S. Food and Drug Administration recently approved another GeoVax investigational new drug application, paving the way for additional clinical trials to test the two components of the vaccine in a prime/boost protocol.
Beginning this month, human clinical trials will evaluate the DNA and MVA components of the vaccine in HIV-negative volunteers at several U.S. sites in the HVTN, including the University of Alabama at Birmingham, Saint Louis University, the University of Maryland and Vanderbilt University. The HVTN is funded and supported by the National Institute of Allergy and Infectious Disease of the NIH.
This trial will have two phases: The first will be a dose escalation to evaluate safety and immune responses. Initially, low doses of the two vaccine components will be given to 12 volunteers. If the vaccine proves safe, the vaccine will then be tested at high dose in 36 volunteers. If this again proves safe—and shows good immunogenicity (appropriate response by the immune system) in the dose/escalation studies—a second phase of clinical testing will begin. In this phase, 72 volunteers will be used to conduct the initial studies on optimizing the dosing schedule.
“This will be the first trial combining our DNA prime with the MVA boost in humans,” Robinson said. “As such, it is very important because it will not only affirm the safety of the DNA and MVA in people but also give us the first window on whether our vaccine is eliciting similar immune responses in humans and monkeys. We firmly believe it will, but that proof will be the springboard for further dosing trials and then the all-important efficacy trials.”