Although Many Antibodies Produced, They Fail To Protect Against HIV Infection

March 23, 2011

Researchers have been stymied for years over the fact that people infected with the AIDS virus do indeed produce antibodies in response to the pathogen - antibodies that turn out to be ineffective in blocking infection. Now, scientists at Duke University Medical Center can explain why: Some of the earliest and most abundant antibodies available to fight HIV can't actually "see" the virus until after it's already invaded a healthy cell.

The scientists based their conclusion on the results of a series of crystallography and biochemical experiments that revealed the specific molecular structures different types of antibodies need to have in place in order for them to mount an effective defense.

Previous research had shown that two of the most robust antibodies against HIV - antibodies called 2F5 and 4E10 - target a specific part of the outer coating of the virus called the MPER region of gp41. The antibodies, which operate in a lock and key relationship, are able to latch on to the virus as it reveals this vulnerable part of its structure, referred to as an "Achilles heel" of the AIDS virus.

"What our studies revealed, however, is that the virus actually creates two versions of this 'Achilles heel,' says Barton Haynes, MD, director of the Duke Human Vaccine Institute (DHVI) and the senior author of the study appearing online in Nature Structural & Molecular Biology. "One version is for these rarer, broadly-neutralizing antibodies, and the other is for the more abundant, first-responding antibodies that won't be able to do much good because the Achilles heel isn't detectable to them until the virus has already gained entry."

Nathan Nicely, PhD, the lead author of the study and a member of the DHVI, designed and conducted most of the crystallography studies. "This structure has been difficult to obtain, but now that we have it, it has been instrumental in our understanding why this non-neutralizing antibody interacts with the HIV-1 outer coat."

Haynes says the findings are important because they distinguish what parts of the virus an antibody needs to recognize from those parts that are decoys. "We are homing in on a better understanding of what the immune system needs to do in order to mount an effective defense against HIV."

Notes:

The study was funded by a Collaboration for AIDS Vaccine Discovery Grant from the Bill & Melinda Gates Foundation.

Colleagues who contributed to the study include S. Moses Dennison, Leonard Spicer, Richard Scearce, Garnett Kelsoe, Yoshihiro Ueda, Haiyan Chen, Hua-Xin Liao, and S. Munir Alam, all from Duke.

Source:
Michelle Gailiun
Duke University Medical Center


Ask The Experts On World Aids Day - What Does The Future Hold For AIDS?

March 09, 2011

The London School of Hygiene & Tropical Medicine is hosting an event on World Aids Day, bringing together some of the world's leading experts on the pandemic, to discuss future projections for the AIDS pandemic.

The panel speakers are as follows:

Peter Piot, Director of the London School of Hygiene & Tropical Medicine and former Executive Director of UNAIDS

The session will be moderated by Heidi Larson, Director of aids2031, an independent consortium set up by UNAIDS in 2007 and consisting of partners experienced in AIDS research, policymaking and programme implementation. The consortium was charged with bringing new thinking to a pandemic that is still growing despite great investments and efforts at control. Its focus has been to look at what should be done differently now to radically reduce the numbers of infections and deaths by 2031, the year that will mark 50 years since AIDS was first reported.

The session will also feature a preview of the forthcoming aids2031 book AIDS: Taking a long-term view published by FT Science Press and available from 13 December.

When: 12.30-2.00 pm, 1 December 2010, John Snow Lecture Hall, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT

Future projections

    * Geoffrey Garnett, Professor, Imperial College London, UK, chair of the aids2031 Modelling Group
    * Justin Parkhurst, Lecturer in Health Policy, London School of Hygiene & Tropical Medicine, aids2031 Working Group on Social Drivers
    * Alvaro Bermejo, Executive Director, International AIDS Alliance, aids2031 working group on Financing and costing
    * Peter Colenso, Head of Human Development Department, Policy Division, DFID

Source:
Lindsay Wright
London School of Hygiene & Tropical Medicine


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