AIDSWEEKLY Plus, Monday, 10 February 1997
Daniel J. DeNoon, Senior Editor
Researchers testing a promising HIV vaccine strategy say their approach is ready for efficacy trials.
The approach employs priming immunizations with a recombinant canarypox virus (ALVAC, Virogenetics), dubbed vCP205, followed by boosting immunizations with recombinant HIV gp120 envelope glycoprotein (rgp120MN in MF59 adjuvant, Chiron/Biocine).
Lawrence Corey of the University of Washington, Seattle, and colleagues from the NIAID AIDS Vaccine Evaluation Group (AVEG) reported the latest findings from AVEG study 022 in a late-breaking news session at the Fourth Conference on Retroviruses and Opportunistic Infections, held January 22-26 in Washington, D.C.
"This combination vaccine of recombinant canarypox vaccine followed by gp120 induces both CD8(+) MHC-restricted class I CTL [cytotoxic lymphocytes] killing to HIV proteins and neutralizing antibodies," Corey et al. wrote in their presentation abstract. "Extension of these findings into high-risk populations is warranted."
Canarypox virus represents a safe vector for genes encoding immunizing antigens because the virus is incapable of completing its replicative cycle in mammalian cells. Before replication is aborted, however, the virus expresses early gene products.
The canarypox vaccine, vCP205, expresses the p55 Gag protein, the p15 protease protein, and the transmembrane region of the gp41 glycoprotein from the LAI strain of HIV-1, as well as the gp120 envelope glycoprotein from the MN strain of HIV-1.
The study tested two different dosing schedules in healthy, uninfected volunteers. Participants received 10(5.8) 50% tissue culture infectious doses (TCID[50]) of vCP205 at 0, 1, 3, and 6 months (n=24) or at 0, 1, and 6 months (n=24). Both groups were boosted with gp120 at months 9 and 12.
Corey et al. assessed CTL responses to HIV-1 Gag and envelope proteins, neutralizing antibodies, and toxicity at days 42, 96, 182, 187, 287, and 378.
On at least one occasion, 12 of the 19 (63 percent) subjects who received four doses of vCP205 and nine of the 22 (41 percent) subjects who received three doses of vCP205 exhibited CD8(+) MHC class I restricted killing targeted to HIV proteins.
For these 21 patients, the vaccine elicited only anti-Gag CTL in 11 patients, only anti-Env CTL in four, and both anti- Gag and anti-Env CTL in six.
All 28 subjects tested at day 378 had neutralizing antibodies to the MN strain of HIV-1.
At the 1996 XI International Conference on AIDS, Corey reported four principle results from AVEG 022: 1) the vCP205 vaccine is safe and immunogenic; 2) boosting of vCP205 with rgp120 elicited neutralizing antibodies; 3) CTL responses occurred prior to the appearance of antibody responses; and 4) the 0, 1, 3, and 6 month vaccination schedule tended to be more immunogenic than the 0, 1, and 6 month schedule, but the difference was not statistically significant.
"These results suggest that a vaccine regimen consisting of a canarypox vector followed by a recombinant subunit protein will elicit HIV- specific CTL and neutralizing antibodies in seronegative subjects," Corey said.
He noted that his group currently is conducting a study using a 1-log higher dose of vCP205.
"This study is intended to answer two questions," Corey said. "Will it [the higher dose] increase the frequency and durability of the CTL response? And will boosting it enhance the humoral effects of the subunit vaccine more?"
Corey is the study chair for AVEG 022. AVEG sites participating in this study are the University of Washington, Seattle; Johns Hopkins University, Baltimore, Maryland; the University of Rochester Medical Center, New York; St. Louis University School of Medicine, Missouri; Vanderbilt University, Nashville, Tennessee; and the University of Alabama at Birmingham. - by Daniel J. DeNoon, Senior Editor
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