The traditional model for developing a HIV vaccine involves targeting the adaptive immune system by producing antibodies that neutralise a large range of HIV field isolates. Scientist Philip Johnson and his colleagues are focusing on a new approach, bypassing the adaptive immune system. An adeno-associated virus (AAV) vector is used to transfer genes expressing antibodies or immunoadhesins (antibody-like molecules) with predetermined HIV specificity into muscle. AAVs are commonly used as gene transfer vectors because they generally do not cause disease in primates nor elicit a response from the host’s immune system.Researchers used a model similar to humans for the experiments. Macaques were infected with the simian immunodeficiency virus (SIV). The experiments were based on delivering, via the AAV vector, SIV-specific antibodies directly to muscle, where they would be endogenously synthesised in myofibers (muscle fiber) and distributed into the circulatory system, thereby protecting the macaque against the infection.
Results found that this method generated long-lasting neutralising activity in serum, with complete protection against intravenously-delivered virulent SIV. Two thirds of the infected macaques were protected against the infection, and the entire sample (nine) from AIDS, whereas all six of the control group were infected and two thirds died during the experiment. One intramuscular injection of the AAV vector is believed to direct long-term, continuous expression of the biologically active protein. The experiment also demonstrated that AAV vectors (double-stranded DNA) achieved higher levels of immunoadhesins in serum than traditionally used single-stranded DNA vectors.
The experiment demonstrated a new approach to developing an effective HIV vaccine, avoiding the adaptive immune system and using the SIV model to carry out further testing.
Article
Johnson P. R., Schnepp B. C., Zhang J., Connell M. J., Greene S. M., Yuste E., Desrosiers R. C. & Clark K. R. (May 2009). “Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys” in Nature Medicine, Advance Online Publication (DOI 10.1038/nm.1967).
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From National Geographic: Southwest National Primate Research Center at Southwest Foundation for Biomedical Research in San Antonio http://news.nationalgeographic.com/news/bigphotos/78627061.html
By Jaelle Brealey - 42016029
