Isolation and characterization of monoclonal antibodies elicited by trimeric HIV-1 Env gp140 protein immunogens.
Eleven anti-HIV Env monoclonal antibodies (MAbs) were isolated from mice immunized with soluble Env proteins derived from the clade B Env, SF162, or DeltaV2 (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.
Derby
Nina R
NR
Seattle Biomedical Research Institute, Seattle, WA 98109, USA; Department of Pathobiology, University of Washington, Seattle, WA 98109, USA.
Gray
Sean
S
Wayner
Elizabeth
E
Campogan
Dwayne
D
Vlahogiannis
Giorgos
G
Kraft
Zane
Z
Barnett
Susan W
SW
Srivastava
Indresh K
IK
Stamatatos
Leonidas
L
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000276:immunology* / Q000302:isolation & purification; D003429:Cross Reactions; D018604:Epitope Mapping; D015686:Gene Products, env / Q000276:immunology* / Q000378:metabolism; D006031:Glycosylation; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D054299:env Gene Products, Human Immunodeficiency Virus
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015686:Gene Products, env; D015700:HIV Envelope Protein gp41; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1