Published in The Hindu on December 14, 2011
While a quarter century of single-minded effort to find an efficacious HIV vaccine has met with only a limited success, a team of researchers led by Nobel Laureate David Baltimore has obtained promising results in prevention of HIV infection in mice by adopting a radically different approach. They deployed gene therapy, which is traditionally used for curing genetic diseases. The study builds on the seminal work by Phil Johnson from the Children’s Hospital of Philadelphia who first showed how gene therapy protects monkeys from SIV, a virus that is analogous to HIV. The results of the study were published recently in Nature As a first step, genes from five broadly neutralising antibodies capable of preventing HIV infection were chosen. DNA, which code for the antibodies, were then inserted into the adenovirus-based vectors and injected into the leg muscles of the mice. The muscle cells containing the DNA eventually started producing the broadly neutralising antibodies. Surprisingly, two antibodies were able to prevent HIV infection even when the viral dose was a 100-fold higher than necessary to infect animals, and significantly more than what humans are likely to be exposed to. As the level of protection in mice remained high even at the end of one year, it is presumed that a single injection might be sufficient to produce long-lasting protection against HIV. Clinical trials on humans may follow soon.
While preventive vaccines containing an immunogen (antigen) prime the immune system to produce antibodies against a virus well before the body is naturally exposed to it, the new approach completely bypasses the immune system and presents the body with DNA capable of producing potent antibodies. But the real differentiator is the speed in designing and developing an effective immunisation product. For instance, the antibodies used in the current study are based on more than a dozen broadly neutralising antibodies isolated from HIV-infected individuals who were not on antiretroviral therapy. While the vaccine programme based on these antibodies is yet to design an effective immunogen, scientists using gene therapy have already completed animal studies. Despite the impressive results, there is sufficient reason to be cautious. Similar levels of success may not be seen in humans. But most importantly, once introduced into the body, there is no way of removing the DNA or turning them off, should things go wrong.