AEGiS-11IAC: Identification of the beta 2-m derived epitope responsible for neutralisation of HIV isolates.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Identification of the beta 2-m derived epitope responsible for neutralisation of HIV isolates.

Int Conf AIDS 1996 Jul 7-12; 11:56 (abstract no. Mo.A.1003)
Le Contel C, Galea P, Silvy F, Hirsch I, Chermann JC; Unite de Recherches sur les Retrovirus et Maladies Associees, Marseille, France. Fax: (33) 91 41 92 50.

OBJECTIVE: Specific antibodies against beta 2-microglobulin (beta 2-m) have been demonstrated to precipitate HIV-1 LAV showing that HIV virions carried beta 2-m on their surface. Such antibodies inhibit replication of HIV-1 LAV. We investigated whether beta 2-m could represent a target against all HIV strains and which beta 2-m epitope is responsible for neutralization.

METHODS: Neutralization assays with anti-human beta 2-m monoclonal antibodies (anti-hu-beta 2-m MAbs) were performed with different HIV isolates on peripheral blood lymphocytes culture (PBL). The study included laboratory adapted, Zarian virus HIV-1 NDK, macrophage tropic strain HIV-1 PAR and primary clinical isolates including newly identified viruses from the International HIV-1 Isolates Panel. By using overlapping synthetic peptides (14 aa) derived from the amino acid sequence of the human beta 2-m and their derived shorter forms (7 aa) we determine which epitope prevents neutralization induced by anti-hu-beta 2-m MAbs through a T-cell line cytopathic assay and RT production assay on HIV-infected PBL.

RESULTS: Anti-hu-beta 2-m MAbs B1G6 and B2.62.2 inhibited at 70-95% the production of all tested viruses (100 TCID50 dose) in primary leukocytes. The cytopathic effect of HIV-1 NDK on a T-cell line was inhibited by B1G6 MAb (5 micrograms) and this inhibition was reversed by addition of four specific 14 aa peptides (100 micrograms) derived from the hu-beta 2-m aa sequence. We showed that 3 out of the 4 actives peptides shared a common amino acid motive (PKI). Their shorter forms (7 aa) around the particular proline residu) were more efficiently recognized by B1G6 MAb in an ELISA developped in our laboratory. Theses 3 specific 7 aa peptides (R7V, F7E, S7K) also prevented neutralization of HIV-NDK induced by B1G6 MAb on PBL. Among them R7V, located at the N-terminal part of the beta 2-m, was found to be the most efficient on the virus neutralization.

CONCLUSION: We selected a beta 2-m derived peptide, R7V, which becomes a potential target for vaccine against HIV. Our results suggest that utilization of non-polymorphic human cell protein-derived peptide present on all tested HIV isolates and eliciting universal HIV neutralizing antibodies may constitute a promising vaccine strategy.

Keywords: AEGIS, Epitopes, HIV Antibodies, HIV-1, Antibodies, Monoclonal, Virus Replication, T-Lymphocytes, Virion, Peptides, beta 2-Microglobulin, Macrophages, Human, virology, ICA11KWDaegis,epitopes,hivantibodies,hiv-1,antibodies,monoclonal,virusreplication,t-lymphocytes,virion,peptides,beta2-microglobulin,macrophages,human,virology,ica11

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MoA1003

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