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2010 NIAID Year in Review

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Recent Successes in Developing an HIV Vaccine

New HIV Vaccine Target Revealed by Studies of Neutralizing Antibodies

Researchers have developed new methods to quickly identify neutralizing antibodies against several variants of HIV from around the world. This advance should assist the design of new HIV vaccines that elicit antibodies that protect against a broad array of HIV subtypes.

Source antibodies were derived from the blood of HIV-infected individuals. The scientists first assessed the neutralizing potential of blood samples taken from more than 1,800 HIV-infected individuals from Thailand, Australia, the United Kingdom, the United States, and several sub-Saharan African countries. Those samples that exhibited broad, strong neutralizing activity against subtypes of HIV found outside North America and Europe were selected as sources for generating monoclonal antibodies, or identical clones of the original antibodies.

In the main focus of this study, the scientists used an efficient technique to screen thousands of antibody-containing samples from an African donor, and from those, they isolated two potent antibodies with broadly neutralizing potential. The antibodies are important because they target a stable region of the HIV surface protein called gp120; otherwise, the HIV surface has a high rate of viral mutation that allows HIV to escape traditional immune defenses.

Reference: Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitchan JL, Lehrman JK, Priddy FH, Olsen OA, Frey SM, Hammond PW; Protocol G Principal Investogators, Kaminsky S, Zamb T, Moyle M, Koff WC, Poignard P, Burton DR. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science. 2009 Oct 9;326(5950):285-9.

A computer-generated structure of a neutralizing antibody bound to an HIV surface protein
A computer-generated structure of a neutralizing antibody bound to an HIV surface protein. The colors represent the following:
Tan: The HIV surface membrane protein gp120
Gray: Electron density map of the viral "spike" molecule that includes both viral gp120 and gp41 proteins
Light Green: V1/V2 and V3 loops.
Credit: NIAID

Structural Clue May Help Scientists Design Better AIDS Vaccines

One of the few parts of HIV that does not mutate is the site where gp120, an HIV surface protein, first attaches to human immune cells. Because of gp120’s immutability, this site is potentially a good target for an HIV vaccine. But surprisingly, the vast majority of antibodies that recognize this site do not prevent HIV infection. Researchers at the NIAID Vaccine Research Center recently discovered why. The gp120 molecule rarely appears in the form that enables the virus to infect cells, that is, a cluster of three gp120 molecules aligned into a so-called “functional spike.” Most antibodies that recognize the gp120 binding site can attach to single gp120 molecules but cannot position themselves to bind to the functional viral spike. It is now clear that to block HIV infection, a vaccine must stimulate the immune system to make antibodies that precisely target the vulnerable site on gp120 as it appears in the three-pronged viral spike.

Reference: L Chen et al. Science. 326:1123-27 (2009).

Chen L, Kwon YD, Zhou T, Wu X, O’Dell S, Cavacini L, Hessell AJ, Pancera M, Tang M, Xu L, Yang ZY, Zhang MY, Arthos J, Burton DR, Dimitrov DS, Nabel GJ, Posner MR, Sodroski J, Wyatt R, Mascola JR, Kwong PD. Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science. 2009 Nov 20;326(5956):1123-7.

New Antibodies Block Infection by Vast Majority of HIV Strains

Scientists led by a team from the NIAID Vaccine Research Center (VRC) discovered two potent human antibodies that can stop more than 90 percent of known global HIV strains from infecting human cells in the laboratory. The researchers also demonstrated how one of these infection-preventing proteins accomplishes this feat. These advances have enabled the scientists to design a candidate vaccine that could elicit antibodies similar to the ones they discovered. Such a vaccine may prevent infection by the vast majority of HIV strains worldwide.

The scientists found the powerful new antibodies, named VRC01 and VRC02, using a protein they developed that reacts only with antibodies that bind to the area HIV uses to attach to and infect immune cells. This area, called the CD4 binding site, is one of the few parts of the viral surface that remains nearly constant in HIV strains found across the globe. By attaching to the CD4 binding site, VRC01 and VRC02 block HIV infection by more viral strains with greater overall strength than any previously known antibodies. The researchers examined the atomic-level protein structure of VRC01, enabling them to define how VRC01 works and locate precisely where it attaches to HIV. The new antibodies could be used in the design of not only HIV vaccines, but also microbicides and therapeutics.

References:

Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, Kwon YD, Scheid JF, Shi W, Xu L, Yang Y, Zhu J, Nussenzweig MC, Sodroski J, Shapiro L, Nabel GJ, Mascola JR, Kwong PD. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science. 2010 Aug 13;329(5993):811-7.

Wu X, Yan ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Longo NS, McKee K, O’Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ, Mascola JR. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010 Aug 13;329(5993):856-61.

Last Updated November 10, 2011

Last Reviewed June 03, 2011