AEGiS-AIDSWeekly: Conference Coverage: Strong Promoter Needed for Humoral, Not T-Cell Response

Important note: Information in this article was accurate in April 1999. The state of the art may have changed since the publication date.

Conference Coverage: Strong Promoter Needed for Humoral, Not T-Cell Response

AIDSWEEKLY Plus; Monday, April 12, 1999
Daniel J. DeNoon, Senior Editor

A strong promoter is sometimes good, sometimes irrelevant. Developers of DNA vaccines generally want to increase expression of antigenic genes by linking them to strong promoter sequences. In the test tube, this seems best for all vaccines, including HIV vaccines. But now researchers at the U.S. Food and Drug Administration (FDA) have actually explored the effects of promoter strength on an HIV prototype vaccine in a primate model, and their findings come as a surprise.

"The promoter strength may have little effect on the intensity of the cellular responses generated by an HIV-1 DNA vaccine, whereas the humoral responses seen in vivo correlated with the promoter strength," concluded T.A. Galvin and colleagues of the FDA's Center for Biologics Evaluation and Research (CBER), Bethesda, Maryland.

The researchers reported their findings in a poster presentation to the Second Annual Conference on Vaccine Research, held March 28-30 in Bethesda, Maryland. Galvin et al. constructed DNA encoding HIV gag, env, rev, and vpu genes under the control of two different promoters: the AKV murine leukemia viral LTR (pAKV-NL[delta-pol]) or the human cytomegalovirus (CMV) CMV-IE promoter (pCMV-NL[delta-pol]).

In vitro, the CMV promoter expressed a reporter gene at 10 to 20 times the efficiency of the AKV promoter. When linked to the HIV DNA construct, in vitro production of HIV proteins by transfected cell lines was higher with the CMV promoter. Macaque monkeys produced persistent Gag and intermittent Env antibodies in response to both of the HIV DNA vaccines. But these humoral responses were more robust, and took fewer injections and lower doses of DNA to elicit, in the CMV-promoted versus the AKV promoted vaccine. Interestingly, T-cell proliferative responses to Gag and Env did not differ between the two vaccine groups.

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