Important note: Information in this article was accurate in 2002. The state of the art may have changed since the publication date.
Newsday - February 27, 2002
Laurie Garrett, Staff Correspondent
Merck Pharmaceutical Co. of West Point, Pa., is spending an undisclosed but massive amount of money on projects for creating a viable AIDS vaccine. The latest, very preliminary, results were presented at the Ninth Retrovirus Conference in Seattle yesterday.
Overall, Merck's vaccines - which are used in various combinations - have not managed to raise in monkeys or humans the sorts of immunity that could protect individuals against infection. The products, however, have shown promise in slowing the disease process in already infected animals by boosting one part of the immune system.
One of Merck's DNA vaccines is made up of pieces of HIV genes that target the key control mechanisms for the virus. It also has a vaccine that combines several HIV proteins with an adenovirus [cold virus] that is rendered harmless. It acts as a vector, carrying the proteins into the body where the immune system can see them and respond.
Dr. Emilio Emini, the lead scientist, said yesterday in a keynote speech that in monkeys the vaccine produced "substantial control of virus replication during the chronic phase" of infections. The animals made large numbers of CD8 and CD4 immune system cells, which attacked the virus and limited its spread.
They did not, however, make antibodies that protected against the invading virus, the gold standard of vaccinology.
"Our focus right now is on cellular immune res- ponses, but that's simply because we don't know how to do the antibodies," Emini said in an interview.
The company plans to have vaccinated 600 volunteers - both HIV- negative and infected - by the end of the year. Yesterday, Emini presented results on a vaccine trial exposing 109 HIV-negative volunteers to three DNA-vaccine shots and an adenovirus vaccine boost. Thirty weeks after initial vaccination, 42 percent of the volunteers who received the higher-dose vaccine were producing cellular immune responses against HIV.
Another study of 48 HIV-negative volunteers found 67 percent gave cellular immune responses, but some were reacting not to the HIV components of the vaccine but to the adenovirus vector.
The adenovirus problem may be handled by finding a monkey adenovirus to which humans haven't been exposed, and, therefore, to which they won't be immune. A group from the Wistar Institute in Philadelphia presented evidence yesterday that a chimpanzee adenovirus may be just the ticket.
But all of these therapeutic vaccines have a common problem, which came to light last month as a result of a Harvard University vaccine effort. It turns out these cellular immune-system-boosting vaccines can, indeed, hold viruses down to minimal numbers for long periods of time. But the Harvard group had a monkey develop mutant viruses after a year that were able to bypass the vaccine, overwhelming the animal.
"The troubling story for all of these vaccines is if the virus is present in large enough amounts, it can replicate and escape" the vaccine, Dr. Barney Graham of the National Institutes of Health Vaccine Research Center said in an interview.
Raymond Gilmartin, chief executive of Merck, said in a recent interview that his company "is fully committed to finding an AIDS vaccine. If it isn't this one, which looks exciting, it will be the next. Or the next. But we are committed to going all the way" in this AIDS vaccine effort.
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