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:2/2/2016)... NEW YORK , Feb. 2, 2016 ... healthcare facilities are primarily focused on medical ... that measure point-of-care parameters. Wearable devices that ... a user,s freedom of movement are being ... sensors for human biomedical signal acquisition coupled ...
(Date:2/2/2016)... 2, 2016   Parabon NanoLabs (Parabon) ... Army Research Office and the Defense Forensics and ... of the company,s Snapshot Kinship Inference ... more generally, defense-related DNA forensics.  Although Snapshot is ... appearance and ancestry from DNA evidence), it also ...
(Date:2/1/2016)... 2016  Wocket® smart wallet ( www.wocketwallet.com ) announces the launch of ... Fatone . Las Vegas , where Joey appeared ... Las Vegas , where Joey appeared at the Wocket ... video ad was filmed at the Consumer Electronics Show (CES2016) in ... to meet and greet fans. --> ...
Breaking Biology News(10 mins):
(Date:2/4/2016)... N.J. , Feb. 4, 2016 ContraVir ... focused on the development and commercialization of targeted antiviral ... CEO & Investor Conference 2016, to be held February ... Source Capital Group,s 2016 Disruptive Growth & Healthcare Conference, ... on February 10-11, 2016. James Sapirstein , ...
(Date:2/4/2016)... ... 04, 2016 , ... Franz Inc. , an early ... has been recognized As “ Best in Semantic Web Technology - USA & ... America, it’s our priority to showcase prominent professionals who are excelling in their ...
(Date:2/3/2016)... , Feb. 3, 2016   ViaCyte, Inc ... the first pluripotent stem cell-derived islet replacement therapy ... clinical-stage development, today announced that ViaCyte and Janssen ... of Johnson & Johnson, have agreed to consolidate ... ViaCyte.  The agreement provides ViaCyte with an exclusive ...
(Date:2/3/2016)... , Feb. 3, 2016 Ascendis Pharma A/S ... that applies its innovative TransCon technology to address significant ... an upcoming investor conference.Event:2016 Leerink Partners Global Healthcare Conference ... , Wednesday, February 10, 2016 Time:  , 11:55am ... . --> An audio webcast of this ...
Breaking Biology Technology: