Isolation and characterization of monoclonal antibodies elicited by trimeric HIV-1 Env gp140 protein immunogens

• Published in: Virology (New York, N.Y.) Vol. 366; no. 2; pp. 433 - 445
• Main Authors: Derby, Nina R, Gray, Sean, Wayner, Elizabeth, Campogan, Dwayne, Vlahogiannis, Giorgos, Kraft, Zane, Barnett, Susan W, Srivastava, Indresh K, Stamatatos, Leonidas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.09.2007
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - isolation & purification; Antibodies, Viral - immunology; Antibodies, Viral - isolation & purification; Cross Reactions; env Gene Products, Human Immunodeficiency Virus; Epitope Mapping; Escape; Gene Products, env - immunology; Gene Products, env - metabolism; Glycosylation; gp140 proteins; GP41; HIV; HIV Env trimers; HIV Envelope Protein gp41 - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Infectious Disease; Mice; Molecular Sequence Data; Monoclonal antibodies; Neutralization; Neutralization Tests; V1 loop; V3 loop; Escape; HIV Env trimers; gp140 proteins; V1 loop; V3 loop; HIV; GP41; Monoclonal antibodies; Neutralization
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2007.05.020

Abstract Eleven anti-HIV Env monoclonal antibodies (MAbs) were isolated from mice immunized with soluble Env proteins derived from the clade B Env, SF162, or ΔV2 (a derivative of SF162 lacking the V2 loop). All six anti-gp120 MAbs studied, neutralized SF162 and their activities were dependent by the glycosylation patterns of the V1, V2 or V3 loops. Only one anti-gp120 MAb (an anti-V3 MAb) displayed cross-neutralizing activity, which was influenced by the type of V1 loop present on the target heterologous viruses. None of the five anti-gp41 MAbs studied displayed anti-SF162 neutralizing activity. Our studies indicate that the current limitation of soluble HIV Env gp140 immunogens to elicit robust cross-reactive neutralizing antibody responses is not only due to the elicitation of high titers of homologous antibodies but also due to the elicitation of antibodies whose epitopes are naturally occluded, or not present, on the virion-associated Env.