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JCI table of contents: Dec. 22, 2010
Date:12/22/2010

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View this article at: http://www.jci.org/articles/view/45664?key=02e333e4c3644d7801d4


VACCINES: Boosting anti-vaccine immune responses

Vaccines are one of the most cost-effective ways to prevent disease. It is believed that vaccines that induce potent responses by immune cells known as CD8+ T cells are required if diseases such as malaria, tuberculosis, and HIV/AIDS are to be successfully targeted. A team of researchers, led by Shahram Salek-Ardakani and Michael Croft, at La Jolla Institute for Allergy and Immunology, La Jolla, has now generated data in mice that should help in the future design of vaccines capable of inducing potent CD8+ T cell responses.

Many human vaccine strategies use poxvirus vectors to deliver the immunizing proteins. For safety reasons, such strategies mostly use attenuated poxviruses, but these often induce poor CD8+ T cell responses and do not provide optimal protection. The team sought to understand how virulent viruses induce more potent immune responses than do attenuated viruses by immunizing mice with vaccinia virus strains of differing virulence. The most virulent vectors, which provided the mice with protection from subsequent lethal challenge with vaccina virus, generated potent CD8+ T cell responses as a result of stimulation of OX40 and CD27 proteins on the cell surface of the CD8+ T cells. Consistent with this, low virulence vectors engendered protection only when administered to the mice with a molecule that stimulated OX40.

In an accompanying commentary, Stuart Isaacs, at the University of Pennsylvania, discusses some of the questions that need to be answered before it can be determined if these data will translate into effective human vaccine design and development.

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