Session 49Poster Presentations Vaccines: Clinical Studies Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall D
404 PACTG 326: A Phase I/II Study to Evaluate the Safety and Immunogenicity of Alvac HIV Vaccines Alone and with AIDSVax B/B in Children Born to HIV-infected Mothers: Preliminary Results D. Johnson*1,2, E. McFarland3, P. Muresan4,8, T. Fenton4,8, J. Lambert5, J. McNamara6, E. Hawkins7, P. Bouquin8, J. Read9, S. Estep6, S. Gunurathan10, M. Gurwith11, PACTG 326 Protocol Team12 1Mt Sinai Hosp, Chicago, IL; 2Chicago Med Sch, IL; 3Univ of Colorado Hlth Sci Ctr, Denver; 4Harvard Sch of Publ Hlth, Boston, MA; 5Univ of Maryland Inst of Human Virology, Baltimore, MD; 6Natl Inst of Allergy and Infectious Diseases, NIH, Bethesda, MD; 7Social and Sci Sys, Silver Spring, MD; 8Frontier Sci and Tech Res Fndn, Chestnut Hill, MA; 9Natl Inst of Child Hlth and Human Dev, NIH, Bethesda, MD; 10Aventis Pasteur, Swiftwater, PA; 11VaxGen, Brisbane, CA; and 12Natl Inst of Allergy and Infectious Diseases/NICHD, NIH, Bethesda, MD
Background: ALVAC-HIV vCP1452 (1452) (Aventis Pasteur) vaccine is a modified recombinant Canarypox virus expressing products of HIV-1 env, gag, nef and pol genes. AIDSVAX B/B (B/B) (VaxGen) is a bivalent vaccine containing 2 different subtype B gp 120 antigens.
Methods: PACTG 326, a randomized, placebo controlled, double-blinded infant study has enrolled 29 mother-infant pairs into 1 of 4 cohorts: 1) 1452 alone; 2) 1452 + B/B; 3) saline placebo; and 4) saline placebo and alum placebo. Subjects were given 1,452 or saline placebo doses at wks of life 0, 4, 8, 12, with the 1st dose given within 72 hrs of life. Those receiving B/B or alum placebo received them at wks 8, 12. Subjects are monitored for local/systemic toxicity and for immunogenicity. Lymphoproliferative (LP) responses to gag (p24) and env (gp160) antigens are measured, as are cytotoxic T-cell (CTL) responses to gag, env, and a hybrid of RT/nef. For LP responses, PBMC are stimulated with antigen and harvested at 6 days after pulsing with 3H-thymidine; a stimulation index (SI) = 3 defines a positive response. For CTL responses, PBMC are stimulated with inactivated autologous B-lymphoblastoid cells infected with recombinant vaccinia vectors and tested for lytic activity by 51 Cr release assay. An assay is positive if HIV-specific lysis is = 10% for at least 2 E:T ratios; and excluded if the highest E:T is < 25:1.
Results: Twenty-nine (29) infants have received 92 doses. Three (3) subjects experienced grade 3 vaccine-associated local/systemic complications (induration at the vaccine site; pain at vaccine site; fever of 103.3° F). Interim summary of LP responses measured at wk of life 6, 10, 14, 24, or 52 shows in the 1452/placebo subjects, 4/9 responded to env, (2/9 responded at 2 time points) and 2/9 responded to gag (no repeat responders). In 1452/placebo + B/B/placebo subjects, 8/9 responded to env, (4/9 responded at 2 time points) and 3/9 responded to gag (no repeat responders). Evaluable CTL: in the 1452/placebo subjects (n = 7), CTL data are available for env, gag, and hybrid RT/nef antigen at 22, 23, and 23 time points, respectively. One (1) subject, at baseline, responded to env. In the 1452 + B/B/placebo subjects (n = 7), CTL data are available for env, gag, and hybrid RT/nef antigen at 20, 23, and 18 time points, respectively. One (1) subject responded at wk 52 to the hybrid antigen of RT/nef and 1 responded at wk 24 to gag and env.
Conclusions: Interim blinded results suggests 1452 and B/B are safe and immunogenic in infants.
