12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 48

Elizabeth McFarland¹, D Johnson^2,3, P Muresan⁴, T Fenton⁴, J McNamara⁵, E Hawkins⁶, B Heckman⁷, J Read⁸, S Estep⁵, M Gurwith⁹, S Gurunathan¹⁰, J Lambert¹¹, and Pediatric AIDS Clinical Trials Group 326 Protocol Team
¹Univ of Colorado Hlth Sci Ctr, Denver, USA; ²Sinai Children's Hosp, Chicago, IL, USA; ³Rosalind Franklin Sch of Hlth and Sci, Chicago, IL, USA; ⁴Frontier Sci & Tech Res Fndn, Harvard Sch of Publ Hlth, Boston, MA, USA; ⁵NIAID, Bethesda, MD, USA; ⁶Social & Sci Systems, Inc, Silver Spring, MD, USA; ⁷Frontier Sci & Tech Res Fndn, Amherst, NY, USA; ⁸NICHD, NIH, DHHS, Bethesda, MD, USA; ⁹VaxGen, Brisbane, CA, USA; ¹⁰Aventis Pasteur, Swiftwater, PA, USA; and ¹¹Univ of Maryland Inst of Human Virology, Baltimore, USA

BACKGROUND: This study immunized infants born to HIV-infected mothers with a prime-boost regimen. ALVAC-HIV vCP1452 (1452) vaccine is a recombinant canarypox virus expressing products of HIV-1 env, gag, nef, and pol genes. AIDSVAX B/B is a bivalent vaccine containing 2 different subtype B gp120 antigens. Vaccination at birth has the potential to reduce breast milk transmission.

METHODS: This randomized, placebo-controlled, double-blinded study, enrolled mother-infant pairs into 4 cohorts: 1452 alone; 1452 + AIDSVAX B/B; saline placebo; and saline placebo and alum placebo. Within 72 hours of life and at 4, 8, and 12 weeks of age, 1452/placebo was given to infants. AIDSVAX B/B or alum placebo was given at weeks 8 and 12. Subjects were monitored for local/systemic toxicity, lymphoproliferative responses to gag and env and cytotoxic T cell (CTL) responses to gag, env, and RT/nef. For lymphoproliferative responses, determined by ³H incorporation assay, a stimulation index ≥ 3 defined a positive response. For CTL, determined by ⁵¹Cr-release assay, an assay was positive if HIV-specific lysis was ≥ 10% for at least 2 effector:target ratios.

RESULTS: Of the 30 infants who received 102 doses, 3 subjects experienced grade 3 vaccine-associated complications (induration at the vaccine site; pain at vaccine site; fever of 103.3 F). Lymphoproliferative responses and CTL were measured at weeks 6, 10, 14, 24, 52, and 104. Cumulative lymphoproliferative responses (number positive/number tested) were higher in the boosted arm, shown in the table below. In the 1452/placebo subjects (n = 12), CTL data are available for env, gag, and RT/nef at 45, 51, and 47 time points, respectively. Of 12 subjects, 2 (17%) had positive CTL responses after baseline: 1 to gag at week 6 and 1 to RT/nef at week 52. One subject had env-specific CTL at week 0. In the 1452 + AIDSVAX B/B/placebo subjects (n = 1), CTL data are available for env, gag, and RT/nef at 43, 47, and 43 time points, respectively. Of 11 subjects, 4 (36%) had positive CTL responses: 2 to RT/nef (week 14 and 52), 1 to env and gag (week 24), and 1 to env at weeks 10 and 104 and to gag at week 104.

CONCLUSIONS: Blinded results in infants suggest that 1452 and AIDSVAX B/B are safe and that immunogenicity is enhanced when given in a prime-boost regimen. Unblinded results will be available at the meeting.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.