LOS ALAMOS, N.M., July 3, 2002 -- Researchers at the U.S. Department of Energy's Los Alamos National Laboratory are using their extensive genetic understanding of the HIV-1 virus -- the most common form of the virus that causes AIDS in humans -- to consider best strategies in the pursuit of creating a vaccine to fight the virus. In an article appearing recently in the journal Science, a team of Los Alamos researchers -- in conjunction with researchers from Duke University, Harvard School of Public Health and the University of Alabama -- suggests using a consensus or genetic ancestor of the HIV-1 virus when developing vaccines, rather than basing vaccines on geographically specific strains of the virus.
"We started working on this problem several years ago in response to a request from the National Institutes of Health to review strategies for HIV vaccine development," said Bette Korber of Los Alamos' Theoretical Division. "Essentially, there is no common strategy for vaccine development. Often, vaccine candidates are selected solely because a particular strain happens to be available. But HIV-1 strains circulating globally are extremely variable genetically, so choosing a locally available virus as basis for a worldwide vaccine may not be the best strategy. Our team has recommended considering alternative strategies of selecting vaccine strains that are central to circulating forms of the HIV-1 virus."
Los Alamos is home to a worldwide database of HIV virus information. Los Alamos' HIV database has extensive information on the genetic structure of the virus and information on various strains and subtypes, among other information. HIV has an extraordinary knack for rapidly changing, making it difficult to control. HIV evolves even within a single individual to become a genetically diverse set of viruses. Because of this genetic variability, development of a vaccine that will attack common vulnerabilities in multiple strains of the virus becomes extremely difficult.
An example of how quickly HIV changes can be illustrated by comparing it with the common influenza virus. Typically, HIV variation within a single infected individual can be as great as the variation of influenza throughout the entire worldwide-infected population in a flu season. In addition, some genetic forms of the virus, called subtypes, are more prevalent than others in some geographic regions. A strain common in South Africa, for example, may be rare in Thailand. This fact compounds the difficulty of developing a worldwide vaccine based on a particular strain.
Subtype C is the most common worldwide, while Subtype B is most prevalent in the United States. What makes HIV-1 even more devious is that the Subtype B virus may evolve differently than the Subtype C virus.
"When we looked at the entire genome of HIV-1, we could see no advantage to using a region-specific virus as a basis for a vaccine," said Brian Gaschen of Los Alamos' Theoretical Division and lead author of the Science article. "Then we started thinking about using a 'consensus sequence' of the virus as a basis for a vaccine. A consensus sequence in effect is a modeled virus which incorporates the most common amino acid found at each location within a viral protein as its basis."
The Los Alamos research team recommended using a consensus sequence obtained from the Subtype C of the HIV-1 virus as a basis for vaccines in regions where the C subtype is most prevalent. Alternatively, they considered using a "vaccine cocktail" to increase the efficacy of the vaccine and to reduce the chances that the virus will evolve into a resistant strain before it is destroyed.
"We hope that this work will help provide a baseline strategy for vaccine development," Gaschen said.
The Los Alamos team includes Gaschen, Korber, Jesse Taylor, Karina Yusim, Brian Foley, Dorothy Lang and Tanmoy Bhattacharya, all of the Theoretical Division. The team also includes Feng Gao and Barton Haynes of Duke University; Vladimir Novitsky of the Department of Immunology and Infectious Diseases, Harvard School of Public Health; and Beatrice Hahn of the University of Alabama at Birmingham.
###Key elements of this research were funded by Laboratory Directed Research and Development. In addition, programmatic support was provided through the NIH-DOE interagency agreement supporting the HIV Databases.
Los Alamos National Laboratory is operated by the University of California for the National Nuclear Security Administration (NNSA) of the U.S. Department of Energy and works in partnership with NNSA's Sandia and Lawrence Livermore national laboratories to support NNSA in its mission.
Los Alamos enhances global security by ensuring the safety and reliability of the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and solving problems related to energy, environment, infrastructure, health and national security concerns.
Materials provided by Los Alamos National Laboratory. Note: Content may be edited for style and length.
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