United Press International - Saturday, 10 February 2001
Joe Grossman, UPI Science News

Two types of HIV vaccine are in human experiments:

-- Most stimulate antibodies which then stand ready to attempt to neutralize a specific invader, such as a virus. This type of HIV vaccine generally elicits antibodies that are specific for only one subtype of human immunodeficiency virus, and even just a few HIV variants within that subtype.

-- Others increase numbers of cytotoxic killer T cells in the immune system, encouraging them to track down and destroy the virus. Some, but by no means all, researchers believe such that vaccines offer hope for broader reactivity.

"The bottom line is that we don't really know yet, until after some trials are done, whether the genetic variation is going to be a limitation for vaccines," said Barney Graham, director of the AIDS Vaccine Evaluation Unit at Vanderbilt University Medical Center, Nashville.

"There's pretty good evidence that a T-cell response elicited by one strain (subtype) will have cross protection against other strains," Graham told United Press International in a telephone interview. "If the vaccine is dependent on the antibody response, unfortunately the antibody response is very type-specific. And in that case if antibody is really needed for vaccine protection then genetic variation is going to be a big problem."

"Virus variation is a major challenge to the development of an HIV vaccine," agreed pathologist Joseph Sodroski of Dana-Farber Cancer Institute and Harvard University, Boston. "If you look at what people have elicited in terms of (antibody responses to HIV) envelope proteins so far, the responses have been pretty narrow.

"If they're pretty narrow then you've got to worry about strain variation in every new testing site and every site where you want to use a vaccine, which would be extremely formidable," asserted Sodroski, whose focus is HIV envelope proteins.

Theory will meet practice this November, when researchers release interim results from the first large-scale HIV vaccine trials. Eight thousand high-risk vaccine volunteers in the United States and Thailand have taken an antibody vaccine, and blood analysis will measure how broadly the vaccine has protected.

The U.S. formulation is designed to create immunity to two variants of the B subtype, the most common subtype in the U.S. That in Thailand is aimed at two subtypes prevalent there, B and E.

Subtypes B and E together comprise about 14 percent of HIV infections in the world. Subtypes A, C and D make-up about 84 percent of all infections, worldwide. Some countries tend to have one or two HIV subtypes, but a number of countries have more than five subtypes.

Don Francis, president of VaxGen, the company conducting the trials in both countries, told UPI, "I do think that the subtype variation of HIV is certainly one of the major challenges that we have to confront, but it is not a new issue. It is really very similar to other viral and bacterial infections."

VaxGen is also designing a vaccine for the C subtype, Francis added.

Tomas Hanke, a senior scientist at Oxford University's Human Immunology Unit, in England, told UPI, "For antibody vaccine I think the clade differences will have to be considered more carefully than the cytotoxic T-cell responses, although there are some important differences among clades in terms of T cell responses, there is also cross reactivity."

While hoping for a vaccine, however, many health-care professionals are worried more about today.

"Effective vaccines at this point are a distant hope," said Vincent Idemyor, a clinical pharmacologist on staff at Advocate Bethany Hospital in Chicago. "We must focus now on delivery of therapeutic drugs to HIV infected people, most particularly in medically under-served areas of the world."

Indeed, "people can't afford to wait five or seven years for vaccines" in sub-Saharan Africa, declared Anne-Valerie Kaninda of Doctors without Borders. "There are more than 25 million people infected (there) right now."

The urgent needs now are medications for infected people and preventive services for those at risk, added Kaninda, who has worked in medical clinics in several countries in Africa.
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