AIDSWEEKLY Plus, Monday, 23 June 1997
Daniel J. DeNoon, Senior Editor
A naked DNA vaccine encoding attenuated versions of HIV-1 accessory genes elicits both humoral and cellular anti-HIV immune responses in animal studies.
The findings suggest improvements for the naked DNA vaccine under development by Apollon Inc., Malvern,, Pennsylvania, in collaboration with researchers at the University of Pennsylvania, Philadelphia. This vaccine, which encodes the HIV-1 gp160 envelope precursor glycoprotein, entered a Phase I clinical trial in 1996.
The new studies by University of Pennsylvania researchers Velpandi Ayyavoo and colleagues suggest that addition of accessory genes could greatly improve vaccine efficacy. They reported their findings in a poster presentation to the 9th Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS (NCVDG), held May 4-7, 1997, in Bethesda, Maryland.
"Our goal is to design an effective genetic HIV vaccine which includes the accessory genes as part of a multi- component genetic immunogen," Ayyavoo et al. wrote in their poster abstract.
Few candidate HIV vaccines have attempted to elicit immune responses to HIV's so-called accessory genes, which express the regulatory proteins Vif, Nef, Vpr, and Vpu.
Ayyavoo et al. molecularly cloned HIV accessory genes from patient isolates. After analysis of sequence variation, they selected prototype genetic variants for animal studies.
Attenuated clones of vif, vpu, and nef induced humoral and cellular immune responses in mice and in non-human primates. These responses correlated directly with DNA dosage and with the number of booster immunizations.
"Evaluation of the cellular responses in vivo using human targets infected with a clinical HIV-1 isolate showed that accessory genes derived from patients can induce immune responses capable of destroying the native HIV pathogen," Ayyavoo et al. wrote. "This strategy can be used generally to develop an effective safe DNA vaccine for any pathogen and these clones should have use as a component of genetic vaccines for HIV-1."
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