T Cell-based HIV Vaccine Candidate Demonstrates Positive Results Science Daily (press release) - Nov 9, 2008 Their results showed that when challenged with a lethal dose of SIV, the vaccinated animals were able to reduce viral replication and to remain healthy for ...
Scientists look to HIV drugs as preventative Los Angeles Times, CA - An early study of tenofovir, for example, showed that it prevented monkeys from getting SIV, the monkey form of the AIDS virus. "But animals are not people, ...
Where did Aids really come from? The Zimbabwe Times, Zimbabwe - Jul 31, 2008 He found 40-year-old papers that refer to the use of ?monkey kidney? - not ape (chimpanzee) kidneys - when macaque cells, which do not carry SIV, ...
Human trials sought for GeoVax AIDS vaccine Gay.com UK, UK - Jul 11, 2008 For a preliminary trial, a pair of monkeys were infected with SIV, or simian immunodeficiency virus, then given the conventional antiretroviral drug therapy ...
58 journalists gather in Mexico City for AIDS conference Jamaica Observer, Jamaica - Jul 29, 2008 The fact that new antibodies do not help control Simian Immunodeficiency Virus (SIV) in monkey, which raises further questions on the ongoing research for a ...
Simple and Choice Reaction Time Performance in SIV-Infected Rhesus Macaques - JK Marcario, LAM Raymond, BJ Mckiernan, LL … - AIDS Research and Human Retroviruses, 1999 - liebertonline.com ... a re- REACTION TIME DEFICITS IN SIV-INFECTED MONKEYS 573 FIG. 1 ... AQ20), these
REACTION TIME DEFICITS IN SIV-INFECTED MONKEYS 575 Page 6. T ...
Long-term follow-up study on SIV intestinal proviral load in rhesus macaques - A Didier, H Petry, C Stahl-Hennig, M Schafer, U … - J Med Primatol, 2000 - Blackwell Synergy ... Fig. 4. Results of the ANOVA for the intravenously infected monkeys. Fig. ...SIV intestinal
proviral ... r=-0.29 (n=20) r=-0.48 (n=7) r=0.12 (n=7) r=-0.27 (n=6) ...
Monkeys Vaccinated Against SIV
Survive Longer After Infection
Results of two new studies sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health (NIH), suggest that even if an HIV vaccine offers imperfect protection against the virus, it might provide vaccinated individuals with an important benefit: a significant survival advantage after infection.
Such a survival advantage was observed in monkey studies conducted by two teams of researchers, one led by Norman L. Letvin, M.D., of Beth Israel Deaconess Medical Center , Harvard Medical School and the NIAID Vaccine Research Center (VRC), and the other by Mario Roederer, Ph.D., of the VRC. The researchers found that monkeys vaccinated against simian immunodeficiency virus (SIV)—a close relative of HIV that causes an AIDS-like disease in monkeys—and then exposed to the virus survived significantly longer than unvaccinated animals exposed to SIV.
“The worldwide need for an HIV vaccine is profound,” says Elias A. Zerhouni, M.D., director of the NIH. “In 2005, more than 11,000 people became infected with HIV every day. If that rate continues unchecked, the virus is going to infect another 40 million people during the coming decade.”
“Although our ultimate goal is to have a vaccine that completely blocks HIV infection, this research suggests a potential benefit of even a partially effective vaccine,” says NIAID Director Anthony S. Fauci, M.D.
Published in this week’s issue of Science and this month’s issue of the Journal of Experimental Medicine, the studies also identified a measurable marker of SIV vaccine effectiveness in monkeys—something known as an immune correlate of vaccine efficacy. Further study is needed to determine if the immune correlate could predict the effectiveness of a vaccine against HIV in humans.
“Having an immune correlate of vaccine efficacy could markedly reduce the time it takes to evaluate whether a candidate HIV vaccine works in people,” says VRC Director Gary
J. Nabel, M.D., Ph.D. “The significance of this discovery is clearly worth evaluating in humans and may considerably accelerate future efficacy trials.”
The SIV vaccine regimen used in the two studies was a simplified version of a preventive human HIV vaccine strategy developed by VRC scientists and currently undergoing Phase II human clinical trials in the United States, the Caribbean and sub-Saharan Africa. Current plans call for testing the efficacy of the vaccine in large-scale human clinical trials some time next year.
To examine the theory that some imperfect HIV vaccines may still allow infected people to live longer and healthier lives, Drs. Letvin and Roederer and their colleagues sought to determine if SIV vaccines confer such a survival advantage to monkeys.
They found that the best way to predict survival after a vaccinated monkey is infected with SIV is by measuring, early in infection, levels of a specific subset of immune cells known as the memory CD4+ T cells. Memory CD4+ T cells are T cells that have been activated by bacteria and viruses upon first exposure and are primed to act more quickly upon reinfection. Of the approximately one trillion T cells in the average adult, more than half are memory cells.
Normally, a rapid and significant loss of these memory CD4+ T cells occurs early on in SIV infection: about ten days into the infection, when the levels of virus in the bloodstream are at their peak, up to 80 percent of the memory CD4+ T cells in some tissues became infected, and ultimately, nearly all of those memory CD4+ T cells are lost.
But vaccinating the monkeys can lessen this damage to the immune system, Dr. Roederer and his colleagues found. In their study of six vaccinated monkeys and six unvaccinated monkeys exposed to SIV, the vaccinated group had about 3 to 5 times fewer memory CD4+ T cells infected and destroyed. “If the virus wipes out only a fraction of the memory CD4+ T cells that it might otherwise destroy, that should allow [the animals] to live longer,” Dr. Roederer says. Likewise, he adds, if HIV vaccines can prevent the destruction of these memory cells in humans, it may be possible to provide people with longer, healthier lives.
In Dr. Letvin’s study, he and his colleagues looked at the effect of preserving the memory CD4+ T cells over the long term. A total of 30 monkeys—24 vaccinated and six unvaccinated controls—were infected with SIV and followed for nearly three years. The vaccine helped control the infection for the first 112 days, but thereafter, the virus levels and total CD4+ counts in the vaccinated and unvaccinated animals did not differ significantly.
But the vaccine protected the memory CD4+ T cells from the virus early on, and the levels of memory CD4+ T cells remained at significantly higher levels in the vaccinated animals for the 850 days they were studied.
“This [early protection] had huge consequences for the development of disease,” says Dr. Letvin. “When infection did occur, the monkeys preserved their memory CD4+ T cells better and lived longer.”
Moreover, the researchers found that measuring a subset of the memory CD4+ T cells, so-called central memory CD4+ T cells, could help predict how the monkey would fare in the long run. Since these new studies indicate that the central memory CD4+ T cell counts appear to be a crucial predictor of long-term health, blood samples from human clinical trial participants might now be examined for this marker. That way, says Dr. Letvin, scientists can gauge how well a vaccine will perform simply by measuring the central memory cell levels in the first few months after infection.
NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.
The National Institutes of Health (NIH)— The Nation's Medical Research Agency—includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov
###
References:
N Letvin et al. Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science DOI: 10.1126/science.1124226 (2006).
J Mattapalli et al. Vaccination preserves CD4 memory T cells during acute SIV challenge. Journal of Experimental Medicine DOI: 10.1084/jem.20060657 (2006).
