HIV-2 neutralization by intact V3-specific Fab fragments.
The V3 region of both HIV-1 gp120 and HIV-2 gp125 surface glycoprotein has been described as a target for neutralizing antibodies. In this study a conformation-sensitive (3C4) and a linear site-specific (7C8) anti-HIV-2 V3 monoclonal antibody (mAb) were characterized. The neutralization capacity of the purified mAbs and their respective papain-generated Fab fragments was analyzed. The Fabs were further characterized by sequence analysis. Our results demonstrate that neither purified mAbs were capable of neutralizing HIV-2, while intact Fab fragments from both mAbs blocked in vitro infection of HIV-2 isolates. Moreover, the conformation sensitive 3C4 Fab neutralized both subtype A and B HIV-2 isolates and SIVsm. Sequence analysis of the hypervariable regions of 3C4 Fab and 7C8 Fab revealed that the third CDR of the heavy chain (CDRH3) of the antibodies was not as long as many of the previously characterized neutralizing antibodies. Our findings suggest that whole 7C8 and 3C4 mAbs are sterically hindered from neutralizing HIV-2, whereas the smaller size of Fab fragments enables access to the V3 region on the virion surface.
Sourial
Samer
S
Department of Microbiology, Tumor and Cellbiology, Karolinska Institute, Stockholm, Sweden. samer.sourial@astrazeneca.com
Nilsson
Charlotta
C
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D015658:HIV Infections / Q000276:immunology; D015498:HIV-2 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016415:Sequence Alignment; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000302:isolation & purification
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D007140:Immunoglobulin Fab Fragments; D054299:env Gene Products, Human Immunodeficiency Virus