AEGiS-11IAC: AVEU 022: safety and immunogenicity of live recombinant canarypox vector containing the envelope, gag and protease genes of HIV-1 in seronegative adult volunteers.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

AVEU 022: safety and immunogenicity of live recombinant canarypox vector containing the envelope, gag and protease genes of HIV-1 in seronegative adult volunteers.

Int Conf AIDS 1996 Jul 7-12; 11:10 (abstract no. Mo.A.282)
Corey L, Weinhold K, McElrath J, Excler JL, Duliege AM, Clements ML, Belche R, Dolin R, Graham B; NIAID AVEU, Univ. of Washington, Pasteur Merieux Corp. and The Biocine Corp., Seattle, WA. Fax: 1-206-621-4178. E-mail: lcorey@u.washington.edu.

OBJECTIVE: To define the immunogenicity and safety of vCP205, a recombinant canarypox vaccine that expresses the P55 gag gene (LAI strain), P15 protease (LAI strain), gp120 (MN strain), and transmembrane region of gp41 (TM) (LAI strain).

METHODS: Seventy six seronegative (SN) volunteers at low risk of HIV infection, received vCP205 (105.8 TCID50) at 0, 1, 3, 6, or. 0, 1, 6, months followed by 50 micrograms of recombinant gp120 (SF2 in MF-59) at 9 and 12 months. Control patients were administered canarypox vector containing the rabies glycoprotein.

RESULTS: Data are available from the initial 3 doses of the trials, all prior to the gp120 boost. vCP205 was very well tolerated, transient pain at the injection site was reported in 65% of subjects. vCP205 elicited little detectable HIV-specific antibodies, however did induce HIV-1 specific CD8+ CTL activity. After 3 doses, only 10% of vCP205 recipients demonstrated antibodies to HIV-1 peptides, purified proteins or whole cell lysates. CTL activity to HIV-1 was measured using autologous BLCL's stimulated with either vCP205 or a recombinant vaccinia virus containing the vCP05 construct as effectors, and BLCL's infected with vaccinia recombinants containing HIV-1, gag, gp160 or vaccinia alone as the target cells. After 3 doses CTL activity to HIV-gag (greater than 10% lysis over vac control) was detected in 7 of 10 recipients and to HIV-1 env in 1 of 8 recipients. All CTL activity was CD8 restricted. Assessment of the consistency of these responses is underway.

CONCLUSIONS: Three doses of this recombinant canarypox vector containing gag, pol, and env of HIV-1 is eliciting CD8-specific CTL responses to HIV gag in 70% of seronegative healthy recipients. Further data on the cellular and humoral immune responses after boosting with recombinant HIV proteins will be presented. 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 SN subjects.

Keywords: AEGIS, HIV-1, HIV Antibodies, Vaccines, Synthetic, HIV Infections, HIV Protease, Vaccinia virus, Endopeptidases, Safety, Adult, Human, ICA11

960707
MoA282