Human monoclonal antibody that recognizes the V3 region of human immunodeficiency virus gp120 and neutralizes the human T-lymphotropic virus type IIIMN strain.

Abstract

We describe a human IgG1 monoclonal antibody (N701.9b) derived by Epstein-Barr virus transformation of B cells from a human immunodeficiency virusseropositive asymptomatic donor. This antibody was shown to recognize the principal neutralizing domain contained within the V3 region of gpl20 of the MN strain of human immunodeficiency virus and MN-like strains, as determined by binding to the PB-1 fragment of MN gpl20 and to synthetic peptides corresponding to the V3 region of MN and related virus strains. The epitope identified by monoclonal antibody N701.9b was mapped to a segment of V3 containing at least 7 amino acids (amino acids 316-322), which is located in the "tip" and "right" side of the V3 loop of the MN strain. Furthermore, this antibody manifested potent type-specific fusion-inhibitory activity against the MN strain but not against the IUB or RF virus strains. This antibody also neutralized four virus isolates that had MN-like V3 region sequences and failed to neutralize three other strains containing unrelated V3 region sequences. Our findings confirm that the V3 region stimulates type-specific neutralizing antibody during natural human immunodeficiency virus infection in humans. The potential clinical use of this antibody is discussed.

Antigen‐antibody interactions: Elucidation of the epitope and strain‐specificity of a monoclonal antibody directed against the pilin protein adherence binding domain of Pseudomonas aeruginosa strain K

“…Recently, Xing et al (1991) have also reported a minimum epitope sequence of 5 residues for three monoclonal anti-mucine antibodies (BCl , BC2, and BC3), and the number of critical residues found was 4 for BCl and BC2, and 1 for BC3. In addition, the epitope length reported for other monoclonal antibodies falls into the range of 5-10 residues (Anderson et al, 1988;Kovamees et al, 1990;Scott et al, 1990), and the minimum sequence found is between 5 and 7 residues (Anderson et al, 1988).…”

Evolution of the HIV-1 env Gene in the Rag2 −/− γ C −/− Humanized Mouse Model

“…Primary isolates of HIV-1 passaged in cell culture in the absence of neutralizing antibody pressure evolve to become sensitive to a spectrum of heterologous neutralizing antibodies (4,65,99). The antibody 447-52D is specific for a conserved epitope at the tip of the Env V3 loop and neutralizes viral isolates that are (86) and preseroconversion (human pre-topostseroconversion) (83) were measured for the C2-to-V5 region of env. For the postseroconversion data set, the mean distance, based on branch lengths of a maximum likelihood tree, was measured from the consensus at a time point 2 to 5 months postseroconversion for variants sampled at time points 9 to 24 months later.…”

Antibodies to several conformation-dependent epitopes of gp120/gp41 inhibit CCR-5-dependent cell-to-cell fusion mediated by the native envelope glycoprotein of a primary macrophage-tropic HIV-1 isolate

“…However, several other antibodies to linear determinants (especially in the V3 loop) have previously been proven also to be powerful inhibitors of fusion (see, for example, ref. 45). Thus it is likely that the lack of activity of certain of our mAbs results from a restricted-type specificity, and that inhibition of fusion would indeed be possible with isolate-specific, high affinity antibodies to linear epitopes.…”