There are two major strains of HIV that are known to cause AIDS in humans-HIV-1 and HIV-2. HIV-1 is by far the more prevalent virus and is often referred to as just HIV. HIV-2, on the other hand, has effects similar to HIV-1 but is less infectious, and is primarily restricted to western parts of Africa. The published research was conducted on the HIV-1 virus, which has infected about 1 percent of the world's population since it crossed over from chimpanzees to humans sometime during the 20th century.
The HIV virus is a retrovirus that attacks essential components of the immune system, including helper T cells (also called CD4+ T cells), which are crucial for mounting an immune response. Depletion of these cells leads to a battery of infections and symptoms collectively called acquired immunodeficiency syndrome (AIDS).
HIV is a roughly spherical enveloped virus with tiny spikes protruding from its envelope. Three copies of a protein called gp120, contained in these spikes, allow the virus to attach and fuse to host cells. Such fusion is followed by entry of the genetic material of the virus into the cells, where it can later direct the cellular machinery to make more copies of itself. These spikes are targets for attack by antibodies, which are proteins produced by the body to neutralize external agents like bacteria and viruses. However, the HIV envelope proteins show remarkable diversity and flexibility, making it difficult for antibodies to bind to their exteriors. Such evasion strategies are partly responsible for the success of the HIV virus in infecting host cells.
Scientists headed by Peter Kwong investigated the binding of the envelope protein gp120 to a protein on helper T cells called CD4. Using crystallography techniques, the researchers obtained images of gp120 binding to CD4, enabling them to pinpoint a key site on gp120 that is accessible to antibodies before HIV infects cells. The authors show that this site, essential for the attachment of gp120 to CD4, has a fixed invariant conformation unlike other sites on gp120, and could serve as a potential target candidate for future vaccine development.
An antibody developed earlier called b12, which has shown promise as a means of combating HIV, was also found to bind to the key site on gp120. Thus, the researchers believe b12 can access and disable the critical HIV target (by preventing gp120 from binding CD4), and a vaccine that stimulates the body to produce b12 antibodies could be an effectual means of neutralizing HIV. The b12 antibody is already known to protect macaque monkeys from infection by the related simian-human immunodeficiency virus.
In a press release covered by Reuters, Kwong said, "Having that site and knowing you can make antibodies against it means that a vaccine is possible [...] It doesn't say we've gotten there. But it's taken it off the list from an impossible dream and converted it to something that is a (mere) technical barrier." Dr. Gary Nabel, coauthor of the paper, concurred with Kwong's statement, stating that "this is certainly one of the best leads to come along in recent years."
Dr. Anthony Fauci, director of the NIAID, added, "I don't think there's any one particular thing that, in and of itself, is the show-stopper. But I don't think we could really make substantial, fundamentally scientifically based progress until we got this very important information."
While HIV transmission is preventable in theory, the virus is likely to continue infecting millions of people around the globe in the absence of any effective vaccine. Now Kwong and his colleagues offer another strategy for fighting HIV, and future animal tests are likely to further address the efficacy of a b12 antibody-based approach.