AEGiS-13IAC: A Phase 1 study of the safety and immunogenicity of an HIV-1 alvac vaccine in children born to HIV infected mothers: preliminary results.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

A Phase 1 study of the safety and immunogenicity of an HIV-1 alvac vaccine in children born to HIV infected mothers: preliminary results.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrC558)

Lambert J, Johnson D, McFarland E, McNamara J, Muresan P, Curd J, El Habib R, Caudrelier P, Fenton T
J. Lambert, University of Maryland, Institute of Human Virology, W Lombard St 5th Fl RM 548, Baltimore MD 21201, United States, Tel.: +1 410 706 4604, Fax: +1 410 706 4619, E-mail: lambert@umbi.umd.edu

BACKGROUND: ALVAC-HIV vCP205 (Aventis Pasteur) is a recombinant Canarypox virus HIV-1 vaccine. We report preliminary safety and immunogenicity data from an ongoing infant trial, including lymphoproliferative (LP) and cytotoxic T-cell (CTL) results. Humoral assays on serum and mucosal specimens are currently being assayed.

METHODS: PACTG 326 has randomized 27 mother-infant pairs into one of 3 vaccine cohorts: (1) vCP205 10 5.8 TCID50/ml, n = 9; (2) vCP205 10 6.3 TCID50/ml, n = 11; and (A) saline placebo, n = 7. Doses are given at weeks 0, 4, 8, 12 of life, the first dose within 72 hours of birth. Subjects are monitored for local and systemic toxicity, and immunogenicity, the latter by antibody titer (ELISA, neutralizing, and salivary IgA), lymphoproliferative (LP), and cytotoxic T cell (CTL) responses. LP, CTL, and IgA are measured to gag (p24) and envelope (gp160) antigens.

RESULTS: Of 26 evaluable infants who received immunizations, 23 have received 4 doses, 2 have received 3 doses and 1 has received 2 doses. None experienced significant ( é grade 3) vaccine associated local or systemic complications. LP responses after baseline (SI > 3) to gp160, ALVAC and p-24 (using a media control for one SI estimate and a company control for a second SI estimate) were detected on at least one occasion in 1/6, 3/6, 3/6 and 3/6 of the placebo patients and in 9/18, 17/18, 15/18 and 12/18 of the vaccinated patients, respectively. Responses on two or more occasions were detected in 0/6, 0/6, 1/6 and 0/6 of the placebo patients and in 4/18, 15/18, 10/18 and 5/18 of the vaccinated patients, respectively. CTL responses after baseline (to vp1291, vp1174 and vp1287) were detected on at least one occasion in none of the placebo patients and in 5/9, 4/10 and 5/10 of the vaccinated patients, respectively. Responses on two or more occasions were detected in 2/9, 2/10 and 2/10 of the vaccinated patients, respectively.

CONCLUSIONS: vCP is safe and immunogenic in HIV exposed infants. Additional data on serum and mucosal humoral immune responses are underway and will also be presented. Future protocols will evaluate new generation ALVAC products (vCP1452) alone and in combination with a bivalent subunit boost (VaxGen gp120 B/B).

Keywords: AEGIS, AIDS Vaccines, HIV Infections, HIV-1, T-Lymphocytes, Cytotoxic, HIV Seropositivity, Child, Human, Infant
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