New findings suggest strategy to help generate HIV-neutralizing antibodies

Nov 19, 2009

New discoveries about anti-HIV antibodies may bring researchers a step closer to creating an effective HIV vaccine, according to a new paper co-authored by scientists at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Scientists know that an HIV-neutralizing antibody called b12 binds to gp120, an surface protein, at one of the few areas of the virus that does not mutate: the site where gp120 initially attaches to human immune cells. It was thought that exposing the human to this site on gp120 would generate that, like b12, can neutralize HIV. Studies have found that for unknown reasons, however, the vast majority of antibodies that recognize this site do not block the virus from infecting cells. Now a new study solves this puzzle, suggesting that antibodies must home in precisely on the site of initial gp120 attachment to successfully neutralize HIV.

The gp120 protein usually appears on the surface of HIV and on infected cells in inactive forms of viral debris or non-functional viral spikes. Only rarely do gp120 molecules appear on the surface of the virus in a functional viral spike, which contains a cluster of three gp120 molecules, known as a trimer, in specific alignment. HIV uses this functional viral spike to bind to and infect them.

The new study shows that most antibodies able to bind to non-functional forms of gp120 cannot bind to gp120 in the functional viral spike and therefore cannot neutralize HIV. Further, the study demonstrates that the reason most anti-gp120 antibodies similar to b12 cannot bind to the functional viral spike is because of the way these antibodies attach to gp120. A close examination of two such antibodies illustrated that their binding positions on gp120 cause a key portion of the protein either to swing in or flare out in positions incompatible with the trimer structure. In contrast, the position of b12 antibody binding allows gp120 to neatly form its normal trimeric structure.

The scientists conclude that generating HIV neutralizing antibodies will require teaching the immune system to make antibodies that precisely target the site of vulnerability on gp120 as it appears in the functional viral spike rather than targeting the plentiful forms of viral debris such as single gp120 .

More information: L Chen et al. Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science, DOI 10.1126/science.1175868 (2009).

Source: NIH/National Institute of Allergy and (news : web)

Explore further: Study models ways to cut Mexico's HIV rates

add to favorites email to friend print save as pdf

Related Stories

Piece of HIV protein may be key to AIDS vaccine development

Feb 14, 2007

In a finding that could have profound implications for AIDS vaccine design, researchers led by a team at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, have generated ...

Exhausted B cells fail to fight HIV

Jul 14, 2008

HIV tires out the cells that produce virus-fighting proteins known as antibodies, according to a human study that will be published online July 14 in the Journal of Experimental Medicine.

Scientists identify new cellular receptor for HIV

Feb 10, 2008

A cellular protein that helps guide immune cells to the gut has been newly identified as a target of HIV when the virus begins its assault on the body's immune system, according to researchers from the National Institute ...

Recommended for you

Obese British man in court fight for surgery

Jul 11, 2011

A British man weighing 22 stone (139 kilograms, 306 pounds) launched a court appeal Monday against a decision to refuse him state-funded obesity surgery because he is not fat enough.

2008 crisis spurred rise in suicides in Europe

Jul 08, 2011

The financial crisis that began to hit Europe in mid-2008 reversed a steady, years-long fall in suicides among people of working age, according to a letter published on Friday by The Lancet.

New food labels dished up to keep Europe healthy

Jul 06, 2011

A groundbreaking deal on compulsory new food labels Wednesday is set to give Europeans clear information on the nutritional and energy content of products, as well as country of origin.

Overweight men have poorer sperm count

Jul 04, 2011

Overweight or obese men, like their female counterparts, have a lower chance of becoming a parent, according to a comparison of sperm quality presented at a European fertility meeting Monday.

User comments : 0