Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team Gains Insight Into HIV Vaccine Failure

22.07.2009
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.”

Study investigators include Natalie A. Hutnick, B.S., and Diane G. Carnathan, M.S., University of Pennsylvania School of Medicine Department of Microbiology and Center for AIDS Research; Sheri A. Dubey, Kara S. Cox, Lisa Kierstead, Michael N. Robertson, M.D., and Danilo R. Casimiro, Ph.D., of Merck Research Laboratories; and Sarah J. Ratcliffe, Ph.D., of the University of Pennsylvania School of Medicine Department of Biostatistics and Epidemiology.

The study was supported by a collaborative grant from the National Institutes of Health to Ertl and Betts.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries – Tomorrow’s Cures. On the Web at www.wistar.org.

Susan I. Finkelstein | Newswise Science News
Further information:
http://www.wistar.org

More articles from Health and Medicine:

nachricht NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University

nachricht How to turn white fat brown
07.12.2016 | University of Pennsylvania School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>