Promising HIV vaccine strategy identified in monkey studies

September 20, 2000

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.

"These animal studies open the window on immune events in early HIV infection and provide a rationale for exploring a new approach to designing HIV vaccines," says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), which funded the research. "The results suggest that using vaccines that stimulate immune responses against virus proteins produced within a few hours after infection, such as Tat, may help control HIV."

"This is the first time someone has investigated the entire cellular immune response during the acute phase of infection," adds Peggy Johnston, Ph.D., NIAID's assistant director for AIDS vaccines and associate director of the Vaccine and Prevention Research Program in the Institute's Division of AIDS. The cellular immune response primarily consists of killer T cells, which attack infected cells rather than target free virus. "If ongoing work by these investigators shows that vaccinating monkeys with SIV Tat induces a massive killer T-cell response that can prevent infection or substantially reduce the amount of virus in monkeys, research on HIV vaccines that incorporate similar targets will be stimulated." Current products in human vaccine trials primarily induce immune responses to envelope or other structural proteins of HIV rather than to functional proteins like Tat, which is required for the virus to replicate.

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."
-end-
The study team, led by professor of pathology and laboratory medicine David Watkins, Ph.D., Todd Allen, Ph.D., and graduate student David O'Connor, conducted the research at the Wisconsin Regional Primate Research Center (RPRC) in Madison. This RPRC is one of eight centers located nationwide that is funded by the National Center for Research Resources, part of the National Institutes of Health (NIH).

NIAID is a component of NIH. NIAID supports basic and applied research to prevent, diagnose and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

References: 1)TM Allen et al. Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viremia. Nature 407:386-90 (2000). 2)BD Walker and PJR Goulder. Escape from the immune system. Nature 407:313-14 (2000).

Press releases, fact sheets and other NIAID-related materials are available via the NIAID home page at http://www.niaid.nih.gov. For additional information on the Regional Primate Research Centers, contact Kathy Kaplan, Information Officer, National Center for Research Resources, 301-435-0888 or visit the NCRR Web site at http://www.ncrr.nih.gov.




NIH/National Institute of Allergy and Infectious Diseases

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.