AIDSWEEKLY Plus, Monday, 17 February 1997
Daniel J. DeNoon, Senior Editor

A naked-DNA HIV vaccine being tested in 15 human subjects with HIV infection appears safe.

The vaccine is being developed by a research team led by David B. Weiner of the University of Pennsylvania in collaboration with Apollon Inc., Malvern, Pennsylvania. Weiner's group has received a four-year, $4.2 million grant from the U.S. National Institute of Allergy and Infectious Diseases (NIAID) to develop naked DNA for use as an AIDS therapy.

The so-called naked DNA vaccine consists of a gene construct, pM160-MN, that expresses the envelope glycoprotein of the MN strain of HIV-1 under the control of the human cytomegalovirus (CMV) promoter gene. The DNA construct is administered directly via intramuscular injection; Weiner's team found that prior intramuscular injections of bupivacaine hydrochloride improved muscle expression of the DNA 20- to 100-fold.

Subjects in the groundbreaking trial all are infected with HIV and had CD4 counts of at least 500 cells/(micro)L at study entry. The dose-ranging study is evaluating 30 (micro)g, 100 (micro)g, and 300 (micro)g doses of the vaccine administered at ten week intervals with a 36-week follow-up period. A booster vaccination is given after four months.

Rob Roy MacGregor of the University of Pennsylvania, Philadelphia, reported initiation of the trial at the 1996 XI International Conference on AIDS. He provided early results in a presentation to the Fourth Conference on Retroviruses and Opportunistic Infections, held January 22-26 in Washington, D.C.

The only adverse event seen to date is a transient rise in creatine kinase levels in three subjects. A fear about DNA vaccines is that subjects will develop destructive antinuclear or anti-DNA antibodies. No such antibodies have been elicited.

The trial is designed to prove the safety of the vaccine; early clinical results are mixed and are not indicative of efficacy.

These data show that two subjects had >=20 percent increases in their CD4 counts while four subjects had a CD4 count decrease. Three subjects had a >=20 percent increase in CD8 counts while four subjects had a CD8 decrease. One patient had a >=0.5 log[10] increase in viral load; one patient had a >=0.5 log[10] decrease.

Perhaps most importantly for the concept of DNA vaccination, patients had dose-related increases in anti-Env antibodies and increased time-dependent cytotoxic lymphocyte (CTL) responses to target cells expressing HIV Env antigen.

MacGregor and colleagues currently are studying cytokine responses to the vaccine. "The vaccine appears safe and capable of inducing specific immune responses to HIV antigens," MacGregor et al. wrote in their presentation abstract.

The vaccine is manufactured by Apollon Inc., Malvern, Pennsylvania. Studies in non-human primates have shown that the vaccine is capable of protecting against lethal challenge with SHIV, a simian/human immunodeficiency virus hybrid.

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