High Viral Load Reduces Vaccine Effect

Researchers seeking to develop vaccines to help treat chronic infections have found that high viral load and limited T cell proliferation tend to reduce the effectiveness of this type of therapeutic vaccination.

Investigators at the Wistar Institute (Philadelphia, PA, USA) and Emory University (Atlanta, GA, USA) created a model for chronic disease by infecting a population of mice with lymphocytic choriomeningitis virus (LCMV). After the infection was established, the animals were injected with a recombinant vaccinia virus expressing the LCMV GP33 CD8 T-cell epitope.

Results published in the July 2005 issue of the Journal of Virology revealed that the vaccine could effectively control the infection as long as the mice contained relatively few virus particles. It was much less effective in animals with heavy viral loads. The latter group of mice also demonstrated sharply reduced proliferative ability in their GP33-specific CD8 T cells.

"In this study, we wanted to look at why therapeutic vaccines are generally less effective than prophylactic vaccines,” said first author Dr. E. John Wherry, assistant professor of immunology at the Wistar Institute. "What we found was that the T cells in the chronically infected mice responded poorly to the vaccine. 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. If we could lower viral load before therapeutic vaccination, we might be able to improve efficacy.”





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Wistar Institute
Emory University