Contributed by guest blogger: Lydia Mendoza ’11
In 2009, it was estimated that 33.3 million people in the world were living with HIV/AIDS. Since the discovery of HIV, more than two decades ago, money has poured into research in the hopes that an effective vaccine might be developed. As of yet a vaccine remains elusive. One reason why it is so difficult to create a vaccine is because HIV is highly mutable and genetically diverse subtypes, or clades, have evolved. A vaccine needs to be able to offer protection from a range of HIV clades.
Normally viral vaccines are based upon neutralizing antibodies, which prevent infection of the host cell. The first attempts to develop neutralizing antibodies against HIV targeted gp120, which is known to play a role in HIV’s ability to enter and infect CD4 t-cells. These attempts have not been successful as of yet because of the gene’s high rate of mutations. However a recent paper has shown that the V3 loop of gp120 is a potential vaccine target.
The strand of protein known as the V3 loop was never thought to be an attractive vaccine target because it is not highly conserved. However, it appears to have conserved structural elements that are involved in interactions with coreceptors. To study whether V3 was a viable vaccine target, a human monoclonal antibody, HGN194 was used. HGN194 was isolated from memory B cells of a person infected with HIV-1 clade AG circulating recombianant form (CRF). HGN194 targets the V3 loop and has been previously shown to neutralize a broad range of neutralization-sensitive and resistant strains of HIV.
The study evaluated whether HGN194 was able to protect rhesus monkeys from an HIV model system. One group of monkeys was injected with HGN194 then they were challenged with a high dose of a clade C SHIV, which is a chimeric simian-human imunodeficiency virus encoding HIV envelope genes in a SIV backbone. The second group of monkeys was also given a high dose of SHIV but was not given the HGN194. The monkeys given the antibody were protected from SHIV infection, and those not given the antibody were infected. The researchers concluded that HGN194, isolated from an HIV-positive individual harboring a clade AG CFR, was able to confer complete cross-clade protection against clade C SHIV.
The antibody apparently latches onto the virus’s V3 loop and prevents the virus from invading cells. This does not mean that this antibody treatment technique is a vaccine for HIV. It does not create long-term protection because the antibodies do not remain active in the body for very long. This is only a first step. A vaccine target has been identified but now scientists must create an antigen that induces formation of an antibody similar in structure to HGN194. There is a lot of work left to be done but this finding hopefully brings researchers much closer to the development of a vaccine.