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 AGIS Group, and l'Agence Nationale de Recherche sur le SIDA.
The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immunodeficiency 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 (rgp160), 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 rgp160 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 and 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Pialoux
G
G
Hôpital de l'Institut Pasteur, Paris, France.
Excler
J L
JL
Rivière
Y
Y
Gonzalez-Canali
G
G
Feuillie
V
V
Coulaud
P
P
Gluckman
J C
JC
Matthews
T J
TJ
Meignier
B
B
Kieny
M P
MP
D016915:AIDS Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D000328:Adult; D000818:Animals; D018150:Avipoxvirus / Q000276:immunology; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002171:Canaries; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015686:Gene Products, env / Q000009:adverse effects / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood*; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D018023:HIV Seronegativity; D006801:Humans; D007117:Immunization, Secondary; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000009:adverse effects / Q000276:immunology*; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*
D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D014614:Vaccines, Synthetic