AIDSWEEKLY Plus, Monday, 24 March 1997
Daniel J. DeNoon, Senior Editor
A mix of DNA vaccines encoding HIV structural, envelope, and regulatory genes could mimic a live attenuated vaccine, Swedish researchers suggest.
A live attenuated SIV vaccine is the only HIV vaccine prototype to show complete protection in primates. But most observers worry that a live HIV vaccine would be too risky for human use: indeed, baby monkeys given oral doses of the SIV vaccine developed AIDS.
Britta Wahren of the Karolinska Institute, Stockholm, Sweden, and colleagues suggested that plasmids containing the HIV-1 nef, rev, and tat regulatory genes; a gene encoding the p24 structural protein; and a gene encoding the gp160 envelope precursor glycoprotein could induce both cellular and humoral anti-HIV immune responses.
They discussed their research in an invited presentation to the Fourth Conference on Retroviruses and Opportunistic Infections, held January 22-26 in Washington, D.C.
"Induction of all these reactivities in the absence of infectivity might give an immune protection similar to that of an attenuated live virus," they wrote in their presentation abstract.
Wahren et al. reported studies showing that serological IgG responses developed in 80 to 100 percent of mice immunized with the DNA-coded proteins. In addition to this humoral response, 40 to 60 percent of the mice developed antigen- specific in vitro T-cell proliferative responses to the antigens and had reactive skin tests against the HIV proteins.
In further studies, they obtained lymphocytes from patients with no specific cytotoxic lymphocyte (CTL) response to recombinant HIV-1 Nef protein. The cells developed CTL responses when exposed to target cells bearing Nef peptides, cells infected with recombinant vaccinia virus expressing Nef, or cells infected with HIV-1.
"Thus, DNA plasmids containing the HIV-1 regulatory genes induced both humoral and cellular immune responses in immunocompetent mice and in immunized humans," Wahren et al. wrote. "Structural genes induce even stronger and more reproducible immune responses."
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