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Understanding Chronic Infections May Help in Developing Therapeutic Vaccines

Vaccines for prophylaxis are well known. Famous vaccines include the ones against tetanus, polio, diphtheria, measles, // mumps etc.; Therapeutic vaccines to cure a condition are more recent innovation. The current vaccines tested in this area include the ones against HIV and hepatitis. The therapeutic vaccines aim to enhance the immune system's ability to combat an infectious agent, such as a virus. Now Researchers are also developing therapeutic vaccines to treat a variety of cancers.

But no dramatic progress has been made in this field. However now, scientists in a recent publication in the Journal of Virology from Wistar Institute and Emory University have shown details about what may prevent the immune system from responding effectively to a therapeutic vaccine during a state of chronic infection. Their findings suggest how scientists might alter therapeutic vaccination approaches to make the immune system respond better.

"In this study, we wanted to look at why therapeutic vaccines are generally less effective than prophylactic vaccines," says E. John Wherry, Ph.D., assistant professor in Wistar's Immunology Program and lead author of the study. Wherry conducted the research as a postdoctoral fellow in the Emory University laboratory of Rafi Ahmed, Ph.D., before joining Wistar earlier this year. "What we found was that the T cells in the chronically infected mice responded poorly to the vaccine."

Specifically, Wherry says, the T cells failed to proliferate, or expand in number. This failure to proliferate seemed to correlate with a high viral load, which suggests several directions researchers might pursue in improving response to therapeutic vaccines.

"The ongoing stimulus to the immune system that occurs in chronic infection seems to prevent the immune cells from responding optimally to a therapeutic vaccine," Wherry says. "If we could lower viral load before therapeutic vaccination, we might be able to impro ve efficacy."

The next step for the research, Wherry says, will be to combine therapeutic vaccines with other modalities that either lower viral load or enhance T cell function, particularly the proliferative capacity of T cells. Possible examples include anti-virals that could be given prior to therapeutic vaccination, or a cytokine that might boost the proliferation or survival of responding cells. While Wherry's primary interest is in chronic infection, he notes that research in this area should inform the design of better therapeutic cancer vaccines as well because many of the deficiencies in immune response are similar whether the antigen confronting the immune system is a virus or a tumor.

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