The effect of sCD4 on the binding and accessibility of HIV-1 gp41 MPER epitopes to human monoclonal antibodies.
Two human monoclonal anti-HIV-1 antibodies, 2F5 and 4E10, were utilized to investigate the accessibility and conservation of gp41 MPER epitopes on five different clades of HIV-1 in the absence and presence of sCD4. The binding of human monoclonal antibodies (mAbs) to HIV-1 was dependent upon the virus clade. Soluble CD4 significantly increased the accessibility of gp41 MPER-binding epitopes on several isolates that previously showed little or no binding with 2F5 and 4E10 mAbs as determined by a modified ELISA-based virus capture assay and surface plasmon resonance. Studies on the relationship between virus binding and neutralization in a TZM-bl pseudovirus assay indicated that in most cases, mAbs that exhibited neutralization also bound the virus. However, neither binding per se nor the total envelope content per virion was a predictor of neutralization. The hidden or conformational gp41 MPER epitopes unmasked by sCD4 may provide additional targets for vaccine design.
Peachman
Kristina K
KK
Henry M. Jackson Foundation for the Advancement of Military Medicine, 1600 East Gude Drive, Rockville, MD, 20850, USA.
Wieczorek
Lindsay
L
Polonis
Victoria R
VR
Alving
Carl R
CR
Rao
Mangala
M
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D057134:Antibodies, Neutralizing / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D005814:Genes, Viral; D015483:HIV Antibodies / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D012995:Solubility; D020349:Surface Plasmon Resonance
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1