Relationship of HIV-1 and SIV envelope glycoprotein trimer occupation and neutralization.
Insights into the process of HIV-1 neutralization may assist rational vaccine design. Here, we compared antibody neutralization against the JR-FL primary isolate and trimer binding affinities judged by native PAGE. Monovalent Fab-trimer binding and neutralization showed a direct quantitative relationship, implying that neutralization begins as each trimer is occupied by one antibody. At saturation, three Fab or soluble CD4 molecules engaged each trimer. In contrast, a maximum of one soluble CD4 molecule bound to functional SIV trimers with a truncated a gp41 tail. Remarkably, soluble CD4 was found to trigger dramatic enhancement of this virus. Unlike Fabs, a quantitative correlation between JR-FL trimer binding and neutralization was unclear for some, but not all IgGs, as neutralization was markedly increased, but trimer affinity was largely unchanged. In addition, only one molecule of certain gp41-specific IgGs appeared to be able to bind each trimer. We discuss the implications of these findings in weighing the relative contributions of size, multivalent binding and other possible effects of IgGs to explain their increased potency.
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
Emma T
ET
Crooks
Pengfei
P
Jiang
Michael
M
Franti
Sharon
S
Wong
Michael B
MB
Zwick
James A
JA
Hoxie
James E
JE
Robinson
Penny L
PL
Moore
James M
JM
Binley
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D009500:Neutralization Tests; D011485:Protein Binding; D015302:Simian Immunodeficiency Virus / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120