title: Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine development.
abstract: An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth of IgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data suggest that the global HIV-1 peptide microarray may be a useful tool for both preclinical and clinical HIV-1 research.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Stephenson
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors.forename: George H
authors.initials: GH
authors.lastname: Neubauer
authors.affiliation: JPT Peptide Technologies, Berlin, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Reimer
authors.affiliation: JPT Peptide Technologies, Berlin, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pawlowski
authors.affiliation: JPT Peptide Technologies, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Knaute
authors.affiliation: JPT Peptide Technologies, Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zerweck
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, United States.
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Ragon Institute of MGH, MIT, and Harvard, Boston, MA, United States. Electronic address: dbarouch@bidmc.harvard.edu.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000939:Epitopes / Q000276:immunology*; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology; D010455:Peptides / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D007074:Immunoglobulin G; D010455:Peptides
keywords: Antibody; Diversity; HIV; Peptide microarray; Vaccine