Researchers at the International AIDS Vaccine Initiative (IAVI), in collaboration with The Scripps Research Institute, Theraclone Sciences and Monogram Biosciences based in US, have identified two potent, broadly neutralizing antibodies (bNAbs) which can disclose vital epitopes on the HIV. The discovery of these novel antibodies could add further vigor to the effort of designing a vaccine against AIDS. The study findings are reported in the recent issue of the journal Science.

Unlike other antibodies (Abs), the broadly neutralizing antibodies are capable of neutralizing a high percentage of different globally circulating HIV types. However, these are induced in a relatively small HIV-infected population. The collaborative research team, through a systematic approach, analyzed the neutralization breadth of such antibodies in the sera samples of approximately 1,800 HIV-1 positive patients (primarily infected with non-clade B viruses) and chose donors for producing monoclonal antibodies (mAb). Following this, the researchers performed high-throughput neutralization screening of Ab-containing culture supernatants of about 30,000 activated memory B cells obtained from an African donor infected with clade-A virus. The study identified two potent mAbs, PG9 and PG16, and reported their key features:
• Higher potency, suggesting that low quantities are effective in conferring protection against the infection
• Greater breadth of neutralization, which is indicative of protecting against a diverse range of HIV subtypes circulating worldwide
• Binds to a novel and potentially more accessible site on the HIV, thereby facilitating vaccine design

The broadly neutralizing epitope, targeted by the newly identified antibodies, was found to be expressed on the trimeric envelope protein, and spanned conserved regions of glycoprotein 120 protein subunit’s variable loops. The findings could provide a framework for developing novel vaccines that elicit bNAb responses.

Immune response analysis in HIV-infected individuals at different periods during the course of infection has shown that, although several types of HIV-specific Abs are produced by the humoral immune system, very few (neutralizing Abs) are capable of exactly binding to and neutralizing HIV. The virus escapes from being neutralized by Abs as:
• HIV mutates at a faster pace
• The virus is coated with bulky sugar molecules, which block the antibodies from reaching their target.

According to the 2007 statistical analysis of the Joint United Nations Program on HIV/AIDS (UNAIDS), the number of people living with HIV/AIDS globally was approximately 33.2 million; documented to be higher than ever before.

Broadly neutralizing antibodies are considered potent, in that they neutralize and help eliminate toxins and pathogenic microorganisms. However, there has been limited success in inducing broadly neutralizing antibodies through the current HIV vaccine candidates. The current discovery of the virus’ Achilles heel could provide a window of opportunity for researchers to design vaccine candidates that elicit broadly neutralizing antibodies against HIV.

References

1. Walker LM, Phogat SK, Chan-Hui PY, et al. Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target. Science. 2009 Sep 3. [Epub ahead of print]

2. Two New Antibodies Found to Cripple HIV. Press Release. International AIDS Vaccine Initiative. Last accessed Sept 10, 2009.