Background: ALVAC-HIV vCP205 (Aventis Pasteur) is recombinant Canarypox expressing gag p55, p15 protein, gp41 anchoring region of HIV-LAI, and gp120 of HIV-1 MN. It is safe and immunogenic in adults.

Methods: PACTG 326 Part I, a randomized, placebo (PL) controlled, double-blinded study, enrolled infants in 3 groups: high dose (HD): vCP205 10^6.33 TCID₅₀/ml; low dose (LD): vCP205 10^6.08 TCID₅₀/ml; and PL: saline. Doses were given at week (wk) 0 (≤ 72 hrs of birth), and at wks 4, 8, and 12 of life. Subjects were monitored for local/systemic toxicity, laboratory abnormalities, lymphoproliferative (LP), and cytotoxic T-cell (CTL) responses at wks 0, 6, 10, 14, 24, 52, and 104. For LP responses, PBMC, stimulated with gag (p24), env (gp160) and control antigens for 6 days, were harvested after pulsing with ³H-thymidine. A stimulation index (SI ≥ 3) defines a positive response. For CTL responses, PBMC were stimulated with inactivated autologous B lymphoblastoid cells infected with recombinant vaccinia vectors expressing gag and env and tested for HIV-specific lysis by ⁵¹Cr-release assay. An assay was defined positive if HIV-specific lysis was ≥ 10% for ≥ 2 E:T ratios.

 Results: Twenty-three (23) infants received all 4 doses; 4 received 1 to 3 doses. No subject experienced a Grade 3 or 4 vaccine-associated adverse event. Of 101 doses, fussiness, pain, and redness were noted after 11 (2 PL), 3 (1 PL) and 2 doses, respectively. LP responses to p24 and gp160 were detected on 2 or more occasions in 4/9 and 1/9 of the HD vaccinees, in 4/9 and 5/9 of the LD vaccinees, and in 0/5 and 0/5 of the PL subjects, respectively. Combining HD and LD, LP responses to p24 and gp160 were detected on 2 or more occasions in 44% (8/18) and 33% (6/18) of vaccinees, respectively. CTL responses to gag and env were detected on at least 1 occasion in 2/9 and 3/9 of HD vaccinees, 4/8 and 1/8 of LD vaccinees, and in 0/5 and 1/5 of PL subjects, respectively. CTL responses to gag and env were detected in 35% (6/17) and 24% (4/17) of all vaccinees and in 0% (0/5) and 20% (1/5) of the placebo recipients, respectively. Of subjects that ever had CTL responses to gag or to env, 50% and 100%, respectively, had a positive response at age 6 wks.

Conclusions: These data suggest that vCP205 is safe and immunogenic in infants. HIV-specific cell-mediated responses could be induced early in life, supporting further study of HIV vaccines in newborns.