Immunization with recombinant canarypox vectors expressing membrane-anchored glycoprotein 120 followed by glycoprotein 160 boosting fails to generate antibodies that neutralize R5 primary isolates of human immunodeficiency virus type 1.

Publication Type
Journal Article
Year of Publication
Bures, R; Gaitan, A; Zhu, T; Graziosi, C; McGrath, K M; Tartaglia, J; Caudrelier, P; El Habib, R; Klein, M; Lazzarin, A; Stablein, D M; Deers, M; Corey, L; Greenberg, M L; Schwartz, D H; Montefiori, D C
AIDS Res Hum Retroviruses
Date Published
2000 Dec 10
Adult; AIDS Vaccines; Amino Acid Sequence; Avipoxvirus; Cell Membrane; Genetic Vectors; Heteroduplex Analysis; HIV Antibodies; HIV Envelope Protein gp120; HIV Envelope Protein gp160; HIV Infections; HIV-1; Humans; Immunization, Secondary; Male; Middle Aged; Molecular Sequence Data; Neutralization Tests; Peptides; Phylogeny; Vaccination; Vaccines, Synthetic

Antibodies generated by candidate HIV-1 vaccines in a phase I clinical trial were assessed for neutralizing activity with a panel of eight well-characterized, genetically diverse clade B primary isolates having an R5 phenotype. The vaccines consisted of one of three different recombinant canarypox vectors expressing membrane-anchored HIV-1(MN)gp120 (ALVAC vCP205, vCP1433, and vCP1452) followed by boosting with a soluble gp160 hybrid consisting of MNgp120 and the majority of gp41 from strain IIIB. Serum samples from a subset of volunteers in each arm of the trial, containing moderate to high titers of neutralizing antibodies to HIV-1 MN, were analyzed. Competition assays with peptides revealed that the majority of neutralizing activity was specific for the MN-V3 loop. Despite MN-specific neutralization titers that sometimes exceeded 1:500, no neutralization of primary isolates was detected and, in some cases, mild infection enhancement was observed. In addition, little or no neutralization of the HIV-1 IIIB heterologous T cell line-adapted strain of virus was detected. These results reinforce the notion that monovalent HIV-1 ENV is a poor immunogen for generating cross-reactive neutralizing antibodies.