Navigation Links
Penn-Wistar team gains insight into HIV vaccine failure
Date:7/20/2009

PHILADELPHIA (July 20, 2009) A team of researchers from The Wistar Institute and the University of Pennsylvania reports new evidence refuting a popular hypothesis about the highly publicized failure in 2007 of the Merck STEP HIV vaccine study that cast doubt on the feasibility of HIV-1 vaccines. The findings were published on-line July 20 in Nature Medicine.

The phase II STEP vaccine trial was stopped after an interim analysis showed no efficacy in preventing HIV infection in at-risk individuals. It was noted that a subset of participants who had previous immunity in the form of neutralizing antibodies to the adenovirus 5 (Ad5) vector used to deliver the vaccine actually showed a trend toward an increased rate of HIV infection. Finding an explanation for this increased susceptibility to infection remains a major focus for HIV vaccine researchers.

These individuals were found to have high blood Ad5 neutralizing antibody (nAb) titers, the main immune gatekeeper in most vaccine strategies. Antibodies produced in response to previous infection neutralize viruses by binding to them and preventing their entry into host cells. They work in concert with other immune cells, including CD4 T-cells, which build a memory bank against future infection. In HIV infection, the virus attaches specifically to CD4 receptors on activated CD4 T-cells, establishing a stronghold and replicating.

Of the STEP findings, many researchers hypothesize that the T-cells of individuals in this high-Ad5-antibody group were activated by the Ad5-vaccine vector, creating more activated CD4 T-cells which then served as targets for the HIV virus to establish an infection.

"Our findings disprove the favored hypothesis," says co-lead author Hildegund C.J. Ertl, M.D., director of The Wistar Institute Vaccine Center. "There was nothing to indicate that pre-existing neutralizing antibodies correlated with numbers of activated CD4 T-cells to Ad5, which could have provided additional targets for HIV infection following subsequent exposure."

Seeking to understand the relationship between previous neutralizing antibodies to Ad5 and Ad5-specific T-cell responses, the team, headed by Michael R. Betts, Ph.D., of the University of Pennsylvania School of Medicine Department of Microbiology, Center for AIDS Research, and Wistar Institute Vaccine Center, analyzed blood samples from 40 healthy participants in the phase I safety trial of the STEP HIV vaccine for immune response to Ad5 particles. The blood samples, which came from individuals with both high and low nAb titers and thus varying degrees of pre-existing neutralizing antibodies to Ad5, had been taken from participants at baseline, before administration of the Ad5 vector vaccine under study. From their current Ad5 assay, the team found no correlation between nAb titers at baseline and CD4 T-cell frequency.

"Ad-specific CD4 T-cells are exceptionally common in humans, regardless of the level of neutralizing antibodies to Ad5," says Betts. "This is probably the major factor that disproves the main hypothesis proposed to explain the STEP trial results."

The team next questioned whether the Ad5-specific CD4 T-cells functioned any differently before or after administering the Ad5 vector. They found no significant difference in activation or expansion of CD4 T-cells in either the high- or the low-Ad5 antibody groups.

"It doesn't appear that vaccination increases the pool of potentially infectable CD4 T-cells in people with pre-existing immunity to Ad5," Ertl says. "When you look at the data together, they suggest we must look elsewhere to explain the link between previous Ad5 immunity and increased acquisition of HIV infection."


'/>"/>

Contact: Susan I. Finkelstein
sfinkelstein@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

Related biology news :

1. Cells united against cancer
2. Voice Biometrics Gains Traction as Most Accurate and Convenient Technology to Secure Customer Privacy
3. Progress Against Malaria: Developments on the Horizon
4. Genes that both extend life and protect against cancer identified
5. Phase 2 of Singapores Biomedical Sciences Initiative gains momentum for clinical research
6. Gamma interferon could aid fight against fungal infections
7. In the laboratory, green tea proves a powerful medicine against severe sepsis
8. Omega-3 fatty acids protect against Parkinsons, study says
9. Protein protects brain against compound in lead poisoning, liver disease
10. Blood pressure drug telmisartan shows powerful activity against stroke
11. CWRU School of Medicine has evidence vaccine against malaria will reduce disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/3/2017)...  Data captured by IsoCode, IsoPlexis Corporation,s ... statistically significant association between the potency of ... objective response of cancer patients post-treatment. The ... cancer patients will respond to CAR-T cell ... to improve both pre-infusion potency testing and cell ...
(Date:3/29/2017)... 2017  higi, the health IT company that operates ... America , today announced a Series B investment ... EveryMove. The new investment and acquisition accelerates higi,s strategy ... transform population health activities through the collection and workflow ... higi collects and secures data today on behalf of ...
(Date:3/24/2017)... 2017 Research and Markets has announced the ... & Trends - Industry Forecast to 2025" report to their ... The Global ... CAGR of around 15.1% over the next decade to reach approximately ... the market estimates and forecasts for all the given segments on ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... ... October 10, 2017 , ... ... targeted antibody-drug conjugate (ADC) therapeutics, today confirmed licensing rights that give it ... Nanoparticle), a technology developed in collaboration with Children’s Hospital Los Angeles (CHLA). ...
(Date:10/10/2017)... ... 10, 2017 , ... Dr. Bob Harman, founder and CEO of VetStem ... The event entitled “Stem Cells and Their Regenerative Powers,” was held ... Harman, DVM, MPVM was joined by two human doctors: Peter B. Hanson, M.D., Chief ...
(Date:10/10/2017)... Calif. , Oct. 10, 2017 SomaGenics ... from the NIH to develop RealSeq®-SC (Single Cell), expected ... for profiling small RNAs (including microRNAs) from single cells ... Program highlights the need to accelerate development of approaches ... "New techniques for measuring levels ...
(Date:10/10/2017)... ... October 10, 2017 , ... The Pittcon ... awards honoring scientists who have made outstanding contributions to analytical chemistry ... Pittcon 2018, the world’s leading conference and exposition for laboratory science, which will ...
Breaking Biology Technology: