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 vect or expressing the human immuno-deficiency virus type 1 (HIV-1) gp160 g ene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injec tions of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rg pl60), were evaluated in vaccinia-immune, healthy adults at low risk f or 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. Loca l 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 H IV-1 MN isolate were detected in 65 and 90% of the subjects after the first and the second rgp 160 booster injections, respectively, Six mon ths after the last boost, only 55% were still positive, Seven of 14 se ra 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 Nort h American primary isolate. Specific lymphocyte T cell proliferation t o 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 fi rst injection, An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as C D3(+), CD8(+), MHC class I restricted. The adjuvant formulation did no t influence significantly the immune responses, This prime-boost vacci ne 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.