Modeling virus- and antibody-specific factors to predict human immunodeficiency virus neutralization efficiency.
Efforts to prevent human immunodeficiency virus type 1 (HIV-1) infection would benefit from understanding the factors that govern virus neutralization by antibodies. We present a mechanistic model for HIV-1 neutralization that includes both virus and antibody parameters. Variations in epitope integrity on the viral envelope glycoprotein (Env) trimer and Env reactivity to bound antibody influence neutralization susceptibility. In addition, we define an antibody-specific parameter, the perturbation factor (PF), that describes the degree of conformational change in the Env trimer required for a given antibody to bind. Minimally perturbing (low-PF) antibodies can efficiently neutralize viruses with a broad range of Env reactivities due to fast on-rates and high affinity for Env. Highly perturbing (high-PF) antibodies inhibit only viruses with reactive (perturbation-sensitive) Envs, often through irreversible mechanisms. Accounting for these quantifiable viral and antibody-associated parameters helps to predict the observed profiles of HIV-1 neutralization by antibodies with a wide range of potencies.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02215, USA; Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Hillel
H
Haim
Ignacio
I
Salas
Kathleen
K
McGee
Noah
N
Eichelberger
Elizabeth
E
Winter
Beatriz
B
Pacheco
Joseph
J
Sodroski
D057134:Antibodies, Neutralizing / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D011487:Protein Conformation; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus