Vaccines designed to trigger an immune response to a small HIV protein called Tat could be a promising way to fend off the virus, intriguing new data suggest. According to a report in this week’s journal Nature, “killer” T cells targeted to the Tat protein can effectively contain simian immunodeficiency virus (SIV), the monkey version of HIV, during the natural course of early infection.
University of Wisconsin researchers found that these Tat-specific killer T cells eliminated the original strain of SIV four weeks after they exposed 18 rhesus macaque monkeys to the virus. The monkeys still had some SIV, but this SIV differed genetically from the original strain. These small genetic changes, pinpointed by the research team and traced predominantly to the Tat protein, provided enough disguise to enable the virus to escape immune attack.
Virus levels peak within weeks after both HIV and SIV infection, but decline soon after when strong killer T-cell responses develop. These responses, however, can hold the virus at bay only so long, eventually losing out to the virus. The power struggle shifts in favor of the virus, the Wisconsin researchers found, because killer T cells pressure the virus to evolve or be destroyed. The challenge remains to design vaccines that induce killer T-cell responses so that the immune system retains the power.
Patricia D’Souza, Ph.D., a microbiologist with NIAID’s Division of AIDS and project officer for this study, says cellular immune responses to HIV and SIV have been difficult to investigate, and only recent research developments made this work possible. “Without the availability of genetically typed monkeys, cloned virus and innovative technology in cellular immunity, it would have been impossible for Dr. Watkin’s group to detect this massive, early Tat-specific immune response.”