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
"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."
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.
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.