New findings from a Philadelphia research team suggest that the virus responsible for rabies may play a significant role in the development of a vaccine to help treat HIV. According to a report published in the April 1st issue of the Journal of Infectious Diseases, a weakened form of the rabies virus can be used to shuttle HIV-related proteins into animals to illicit an immune response capable of slowing or preventing HIV disease progression. The research completed to date does not suggest that it will be effective in terms of preventing HIV in those not already infected.
According to the paper authored by Mathias Schnell, PhD, professor of microbiology and immunology at Jefferson Medical College in Philadelphia, and his colleagues, the theory driving this research was that rabies' vehicles, or "vectors," would help attract a strong immune response without causing disease. Such vectors are based on a type of rabies vaccine strain that has been used for more than 20 years in oral vaccines against rabies in wildlife in Europe.
Dr. Schnell's group began by developing two vaccines, both involving weakened rabies viruses with genomes fitted with viral genes to express proteins similar to those used by HIV. The first vaccine was fitted with Env, a gene that would cause the rabies virus to develop an outer membrane similar to HIV. This would allow the rabies virus to target the same cells used by HIV. The second vaccine was fitted with a simian immunodeficiency virus (SIV) version of HIV's Gag gene, which is needed to make structural proteins for new virus particles.
Four macaques were then immunized with both vaccines, while two animals received only a weakened rabies virus. After Dr. Schnell's group gave the animals an initial vaccination, they then tried two different immune system boosts, but didn't see enhanced immune responses. They then developed a new vector, a viral surface protein from another virus, vesicular stomatitis virus (VSV). Two years after the initial immunization, they gave a booster vaccine with the rabies-VSV vector, and saw SIV/HIV-specific immune responses.
The researchers then challenged the macaques with SIV and measured various parameters of infection, such as CD4 cell counts, viral loads, and antibody responses. Accordingly, the animals given the test vaccine were able to control the infection, whereas the animals that didin't receive the vaccine ended up with high viral loads and low CD4 cell counts.
"We still need a vaccine that protects from HIV infection, but protecting against developing disease can be a very important step," Dr. Schnell says, noting that he and his colleagues aren't sure how long the viral immunity will last. He adds that future studies involving larger groups of animals are needed and, eventually, human studies to show that a rabies-based compound can work as a therapeutic vaccine in HIV-positive people.
Source:
McKenna PM, Koser ML, Carlson KR, et al. Highly Attenuated Rabies Virus-Based Vaccine Vectors Expressing Simian-Human Immunodeficiency Virus89.6P Env and Simian Immunodeficiency Virusmac239 Gag Are Safe in Rhesus Macaques and Protect from an AIDS-Like Disease. J Infect Dis 195(7)980-8, 2007.
