title: The importance of antibody isotype in HIV-1 virus capture assay and in TZM-bl neutralization.
abstract: The binding of murine IgM mAbs to five different clades of HIV-1 was examined using a modified ELISA-based virus capture assay. Two murine multispecific IgM mAbs that exhibit both lipid and gp41 epitope specificities, and one murine IgM mAb that exhibits lipid-binding specificity, were utilized. The binding of the IgG and the IgM isotypes of human mAb 2F5 to clades A through AE were also evaluated. The binding of 2F5 to HIV-1 was dependent upon the antibody isotype. Monoclonal IgM antibodies bound significantly lower amounts of HIV-1 than the corresponding IgG isotype. Although murine IgM mAbs bound HIV-1 to varying degrees in the virus capture assay, they failed to neutralize HIV-1 in a TZM-bl pseudovirus assay. In contrast, 2F5-IgM mAb bound certain HIV-1 isolates, and also neutralized them, although not as efficiently as the 2F5-IgG isotype. Studies on the relationship between virus binding and neutralization in a TZM-bl pseudovirus assay indicated that in most cases, mAbs that exhibited neutralization also bound the virus.
authors.affiliation: Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland, USA.
authors.forename: Kristina K
authors.initials: KK
authors.lastname: Peachman
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wieczorek
authors.forename: Gary R
authors.initials: GR
authors.lastname: Matyas
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
authors.forename: Mangala
authors.initials: M
authors.lastname: Rao
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001681:Biological Assay / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000145:classification* / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000145:classification* / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests / Q000379:methods*; D011485:Protein Binding; D056189:Viral Tropism / Q000502:physiology
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M