A Prime-Boost Approach to HIV Preventive Vaccine Using a Recombinant Canarypox Virus Expressing Glycoprotein 160 (MN) followed by a Recombinant Glycoprotein 160 (MN/LAI)

The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immuno-deficiency virus type 1 (HIV-1) gp160 gene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injections of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rgpl60), were evaluated in vaccinia-immune, healthy adults at low risk for acquiring HIV-1 infection, Volunteers (n = 20) received vCP125 (10(6) TCID50) at 0 and 1 month, followed randomly by rgpl60 formulated in alum or in Freund's incomplete adjuvant (FIA) at 3 and 6 months. Local and systemic reactions were mild or moderate and resolved within the first 72 hr after immunization. No significant biological changes in routine tests were observed in any volunteer. Two injections of vCP125 did not elicit antibodies. Neutralizing antibodies (NA) against the HIV-1 MN isolate were detected in 65 and 90% of the subjects after the first and the second rgp 160 booster injections, respectively, Six months after the last boost, only 55% were still positive, Seven of 14 sera with the highest NA titers against MN weakly cross-neutralized the HIV-1 SF2 isolate; none had NA against the HIV-1 LAI or against a North American primary isolate. Specific lymphocyte T cell proliferation to rgp 160 was detected in 25% of the subjects after vCP125 acid in all subjects after the first booster injection and 12 months after the first injection, An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as CD3(+), CD8(+), MHC class I restricted. The adjuvant formulation did not influence significantly the immune responses, This prime-boost vaccine approach using a nonreplicating recombinant live vector, ALVAC-HIV (vCP125), and an rgpl60 was safe in humans and did induce both humoral and cell-mediated immune responses.