Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Triple-vaccine strategy stimulates strong HIV-specific immune response in monkeys

09.07.2004


Researchers at The Wistar Institute and the University of Pennsylvania report success in monkeys of an innovative triple-vaccine strategy aimed at creating an effective anti-HIV vaccine regimen. In a test of the new approach, the scientists sought to maximize the immune response to a truncated HIV gene called Gag and succeeded in dramatically stimulating the production of CD8+ T cells responsive to Gag. Many scientists believe that CD8+ T cells will be an important key to creating an effective HIV vaccine.

"For a variety of reasons, it may not be possible to create a vaccine that generates antibodies able to neutralize HIV," says Hildegund C.J. Ertl, M.D., professor and immunology program leader at Wistar and senior author on the report published in the July issue of the Journal of Virology. "The next best thing may be to develop a vaccine that stimulates the production of anti-HIV CD8+ T cells, which have been shown in other studies to reduce viral load, although they do not prevent infection. The new vaccine regimen we tested induced unprecedented levels of CD8+ T cells in monkeys."

The experimental vaccines developed by Ertl and her colleagues take advantage of sophisticated bioengineering technologies and the special characteristics of a class of viruses called adenoviruses to create a series of three vaccines that, when given in sequence, build on each other to generate a stronger immune response than might otherwise be possible.



Many current vaccine development programs rely on human adenoviruses engineered to include elements from disease-causing agents, in part because adenoviruses are relatively easy to manipulate in the laboratory and readily enter a wide variety of cells, including important cells of the immune system, to stimulate a vigorous, long-lasting immune response.

A number of these vaccines based on common strains of human adenoviruses, including some against HIV, have returned positive results in early clinical trials. An unaddressed problem with this vaccine-development approach, however, is that many people are exposed to adenoviruses in childhood and carry neutralizing antibodies against the viruses that would interfere with the effectiveness of any vaccine based on them. About 45 percent of adults in the United States, for example, have pre-existing immunity to the most prevalent strains of adenovirus, and similar or higher levels have been reported in other parts of the world.

To circumvent this potential difficulty, the researchers at The Wistar Institute and the University of Pennsylvania developed a series of vaccine vectors based on chimpanzee adenovirus strains, which possess the immunological strengths of human adenoviruses without their drawbacks. Previously published proof-of-principle studies in mice showed that the new vectors were able to avoid the problem of pre-existing immunity.

In the current study, the scientists created three vaccines, each with a different adenovirus as a backbone but all containing the same truncated HIV gene, Gag. Two of the vaccines were based on chimpanzee adenoviruses, and the third was based on a human adenovirus. The vaccines were administered to two groups of four rhesus macaques each. One group received the human adenovirus vaccine first, followed by the two chimpanzee adenovirus vaccines. The other group received one of the chimpanzee adenovirus vaccines first, followed by the other chimpanzee adenovirus vaccine and then the human adenovirus vaccine.

Both triple immunization regimens sparked high frequencies of CD8+ T cells against Gag that remained remarkably stable over time, demonstrating the potential of the new strategy. For eventual clinical use, vaccines incorporating more elements of HIV would be needed to elicit sufficiently broad T-cell responses to be fully effective.

A unique advantage of the triple-vaccine approach tested by the researchers is that it avoids generating pre-existing immunity to the vaccine backbone, which is new to the immune system at each stage of the regimen. The immune system does respond with increasing vigor, however, to the repeating Gag element of the three vaccines.

In addition to Ertl, the other Wistar-based authors on the Journal of Virology study are first authors Arturo Reyes-Sandoval, Ph.D., also affiliated with Instituto Politecnico Nacional in Mexico City, Mexico, and Julie C. Fitzgerald, both of whom contributed equally to the work, as well as Zhi Quan Xiang, M.D., and Yan Li. The University of Pennsylvania co-authors include James M. Wilson, M.D., Ph.D., professor of medicine and medical genetics, Rebecca L. Grant, D.V.M., Soumitra Roy, M.D., and Guangping Gao, Ph.D.

Franklin Hoke | EurekAlert!
Further information:
http://www.wistar.upenn.edu

More articles from Studies and Analyses:

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>