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12:00 AM
 | 
Feb 28, 2005
 |  BioCentury  |  Tools & Techniques

Quelling resistance

With alarms being raised by the so-called highly resistant New York strain of HIV, announcements of new approaches to countering the plasticity of the virus will draw close attention. The Scripps Research Institute, BioInvent International AB, and Bavarian Nordic A/S recently presented three different approaches to overcoming or protecting against resistant strains.

Researchers at Scripps are working backward from a neutralizing antibody to design immunogens that could be part of a prophylactic vaccine that would protect against resistant strains.

BioInvent is developing an anti-tat antibody therapeutic that the company thinks will reduce viral load in HIV patients without promoting resistance, because it works outside of the infected cell.

Meanwhile, Bavarian Nordic is developing a therapeutic vaccine that it says could be used in combination with standard therapy to help maintain low viral load. If the effect is sustained for prolonged periods, the vaccine may help alleviate concerns raised about resistance that has been seen when patients return to treatment after drug holidays.

Using retrovaccinology

The Scripps researchers think they may have found an antibody that will allow them to design antigens for use in a vaccine that will protect against resistant strains of HIV. Scripps professor Ian Wilson calls the process "retrovaccinology," which works backward from an antibody to design the antigen.

In this case, the process began with an antibody isolated from an HIV patient a decade ago. The antibody, called 4E10, has been shown to neutralize about 100 different strains of HIV. It targets a highly conserved region of the HIV gp41 protein, which also is called 4E10.

This month, researchers led by Wilson published in Immunitythe crystal structure of the 4E10 antibody, which is allowing them to "reverse-engineer" a component of a vaccine.

"We are using the 4E10 antibody to find out how to design an effective immunogen to raise the antibody in people," said Wilson....

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