A Cornell medical researcher has been vindicated in his claim that a recently-released HIV vaccine would be unsuccessful after the drug was pulled last month from the market in South Africa.
Dr. Kendall A. Smith of Cornell Weill Medical College explained that the leading pharmaceutical company Merck’s vaccine went on to Stage II testing in South Africa because “the vaccine had no adverse affects in Stage I.”
Smith described that testing the effectiveness of this and all HIV vaccines is so difficult because there is no animal model for HIV. While doctors do test some vaccines on monkeys, because they have SIV (which affects simians as opposed to humans) it is difficult to find matching cures.
Another problem in testing the vaccine is that it cannot be injected into a normal individual before injecting the virus because of ethical considerations. Instead, Smith explained, doctors are forced to wait for a high-risk individual to contract the virus to see if the vaccine will work.
“It takes a lot of money and a long time to be able to find out if the vaccine is going to work or not,” he said.
HIV is a difficult virus for which to create a vaccine because it is constantly mutating. But, Smith said, the virus does have some crucial, non-replicating genes that are important in the creation of the vaccine because they are the genes the immune response is focused on.
Smith tried to explain to Merck that its vaccine would not work because it used a non-replicating viral vector in injecting the vaccine. He said he believed that the adenovirus vector, a replicating vector used as a vaccine for the common cold, would be more successful.
“Most if not all of the people in vaccine development are not immunologists but molecular biologists,” Smith said.
Smith said that Merck ignored his advice went ahead with its testing because the company’s leading molecular biologists were reluctant to listen to the opinion of an immunologist.
Brad Gorter, ’08 said he doesn’t blame Merck for continuing on with its research.
“If they had a panel of reputable doctors saying that it will work and just this one doctor from Cornell said it wouldn't work, you can't fault them,” Gorter said.
“In developing the drug, they probably invested millions, and to just throw it away without trying it would be somewhat ridiculous to some investors and/or executives,” he continued.
Smith said he sees promise in another vaccine and in another leading researcher. Dr. Marjorie Robert-Guroff from the National Cancer Institute (NCI), a branch of the National Institutes of Health in Maryland (NIH), has been developing an AIDS vaccine using a different approach from Merck’s and has been working on her version of the vaccine since 1989.
“We have shown in non-human primate studies that the replicating vector is more immunogenic and elicits better cellular immune responses and primes better antibody responses than the non-replicating one. The Merck approach was focused on inducing immune T cells specific for HIV. We believe T cell responses will be important and necessary for a future vaccine, but also think a successful vaccine will require a component that induces strong antibodies,” Guroff explained.
Guroff is working on her vaccine from the immunologist’s perspective that Dr. Smith believed was missing from the Merck research.
“We believe all components of the immune system will be needed for a successful vaccine: cellular immunity, humoral immunity, mucosal immunity and innate immune responses, as well,” Guroff said.
Using replicating vectors, as opposed to non-replicating vectors, according to Guroff, “[will elicit] cellular immunity and antibodies [and] also act like a natural infection and induce cytokines and co-stimulatory molecules, thereby increasing immune responses and also bringing into play the innate immune system.”
NCI and NIH have previously been the sites of major developments in AIDS research. In the early 1980s, when AIDS was first recognized, Dr. Robert Gallo, working at NCI at the time with Dr. Luc Montagnier, another researcher, co-discovered HIV. Additionally, NIH is the site of the development of the HIV-detecting blood test, designed by Gallo.