title: 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.
abstract: 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.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bures
authors.forename: A
authors.initials: A
authors.lastname: Gaitan
authors.forename: T
authors.initials: T
authors.lastname: Zhu
authors.forename: C
authors.initials: C
authors.lastname: Graziosi
authors.forename: K M
authors.initials: KM
authors.lastname: McGrath
authors.forename: J
authors.initials: J
authors.lastname: Tartaglia
authors.forename: P
authors.initials: P
authors.lastname: Caudrelier
authors.forename: R
authors.initials: R
authors.lastname: El Habib
authors.forename: M
authors.initials: M
authors.lastname: Klein
authors.forename: A
authors.initials: A
authors.lastname: Lazzarin
authors.forename: D M
authors.initials: DM
authors.lastname: Stablein
authors.forename: M
authors.initials: M
authors.lastname: Deers
authors.forename: L
authors.initials: L
authors.lastname: Corey
authors.forename: M L
authors.initials: ML
authors.lastname: Greenberg
authors.forename: D H
authors.initials: DH
authors.lastname: Schwartz
authors.forename: D C
authors.initials: DC
authors.lastname: Montefiori
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D018150:Avipoxvirus / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D020180:Heteroduplex Analysis; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010802:Phylogeny; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D010455:Peptides; D014614:Vaccines, Synthetic