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47 Safety Profile of Preventive Canarypox-Vectored (ALVAC) HIV-1 Vaccines Tested in the US: 1993(2001
M. Keefer*1, R. El Habib2, and the NIAID HIV Vaccine Trials Network
1Univ. of Rochester Med. Ctr., NY, USA and 2Aventis Pasteur, Marcy l’Etoile, France
Background: An acceptable safety profile is a prerequisite for the advancement of candidate HIV vaccines into Phase III efficacy trials. Five different canarypox (ALVAC)-vectored HIV-1 candidate vaccines (vCP125, 205, 300, 1433, and 1452; vCP1452 is being considered for a Phase III study) produced by Aventis-Pasteur (France) have been evaluated by NIAID-supported HIV vaccine trials networks (AVEG, HIVNET, and HVTN) since 1993. All constructs include the gene for HIV-1 envelope, and all except 1 include gag-protease. They also vary in the inclusion of additional pol, nef, and vaccinia E3L and K3L genes. Most have been given as a combination vaccine regimen, usually with rgp 120 (SF-2). All studies included a control arm of ALVAC rabies glycoprotein or ALVAC placebo. Here we describe the safety profile of ALVAC-HIV vaccines in healthy HIV-uninfected human volunteers.
Methods: Volunteers typically received 4 or more intramuscular ALVAC vaccinations. All were evaluated at 0.5, 6(12, 24, and 48 hours post-vaccination for local and systemic reactions. Follow-up visits included symptom-directed physical exams; hemotologic, renal, and liver function tests; and self-report of adverse medical events. Local and systemic reactions are compared among all vaccine and control recipients from 11 Phase I and 2 Phase II trials. Rates of serious adverse event reports (SAEs) are also presented.
Results: 1,579 HIV-negative, healthy volunteers participated in the ALVAC trials (1,192 on ALVAC containing arms and 387 placebo recipients). Statistically significant differences (p < 0.05) are observed between vaccinees and controls for local but not systemic reactions. Among vaccinees (controls), 1.9% (0.8%) had severe pain/tenderness at the site of injection, 2.7% (0.3%) erythema/induration greater than 25 cm2, and 1.8% (1.0%) had a severe systemic reaction (malaise, myalgia, headache, fever, or nausea). Moderate local/systemic reactions were seen in approximately 40%/20% of vaccinees and 20%/20% of controls. The rates of local and systemic reactions were similar among the different ALVAC constructs. Approximately 6% of both vaccine and control recipients reported SAEs. Only 1 vaccinee reported a severe SAE (chills) related to study preparations.
Conclusions: All ALVAC-HIV vaccines, including vCP1452, have a safety profile allowing advancement to larger studies.
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