Featured Research

from universities, journals, and other organizations

Triple-vaccine Strategy Stimulates Strong HIV-specific Immune Response In Monkeys

Date:
July 12, 2004
Source:
The Wistar Institute
Summary:
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.

PHILADELPHIA – 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.

###

Support for the research was provided by the National Institute of Allergy and Infectious Diseases, one of the National Institutes of Health.

The Wistar Institute is an independent nonprofit biomedical research institution dedicated to discovering the causes and cures for major diseases, including cancer, cardiovascular disease, autoimmune disorders, and infectious diseases. Founded in 1892 as the first institution of its kind in the nation, The Wistar Institute today is a National Cancer Institute-designated Cancer Center – one of only eight focused on basic research. Discoveries at Wistar have led to the development of vaccines for such diseases as rabies and rubella, the identification of genes associated with breast, lung, and prostate cancer, and the development of monoclonal antibodies and other significant research technologies and tools.


Story Source:

The above story is based on materials provided by The Wistar Institute. Note: Materials may be edited for content and length.


Cite This Page:

The Wistar Institute. "Triple-vaccine Strategy Stimulates Strong HIV-specific Immune Response In Monkeys." ScienceDaily. ScienceDaily, 12 July 2004. <www.sciencedaily.com/releases/2004/07/040709084550.htm>.
The Wistar Institute. (2004, July 12). Triple-vaccine Strategy Stimulates Strong HIV-specific Immune Response In Monkeys. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2004/07/040709084550.htm
The Wistar Institute. "Triple-vaccine Strategy Stimulates Strong HIV-specific Immune Response In Monkeys." ScienceDaily. www.sciencedaily.com/releases/2004/07/040709084550.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins