Abstract
Strain-specific neutralizing antibodies develop in all human immunodeficiency virus type 1 (HIV-1)-infected individuals. However, only 10–30% of infected individuals produce broadly neutralizing antibodies (bNAbs). Identification and characterization of these bNAbs and understanding their evolution dynamics are critical for obtaining useful clues for the development of an effective HIV vaccine. Very recently, we published a study in which we identified 12 HIV-1 subtype C-infected individuals from India whose plasma showed potent and broad cross-clade neutralization (BCN) ability (1). In the present study, we report our findings on the evolution of host bNAb response over a period of 4 years in a subset of these individuals. Three of the five individuals (NAB033, NAB059, and NAB065) demonstrated a significant increase (p < 0.05) in potency. Interestingly, two of the three samples also showed a significant increase in CD4 binding site-specific antibody response, maintained stable CD4+ T cell counts (>350 cells/mm3) and continued to remain ART-naïve for more than 10 years after initial diagnosis, implying a strong clinical correlation with the development and evolution of broadly neutralizing antibody response against HIV-1.
Highlights
One of the major goals of an human immunodeficiency virus type 1 (HIV-1) vaccine is to induce broadly neutralizing antibodies that can prevent HIV infection [2]
The fifth sample (NAB059) showed an extraordinarily high neutralization potency with a Geometric mean titer (GMT) of 7190, prompting us to categorize this individual as an elite neutralizer
Few studies suggest that evolution of viral variants as well as Broadly cross-clade neutralizing antibodies (bNAbs) takes place simultaneously, and that acquisition of neutralization breadth and potency continue during ongoing HIV-1 infection [48, 49]
Summary
One of the major goals of an HIV-1 vaccine is to induce broadly neutralizing antibodies (bNAbs) that can prevent HIV infection [2]. A strain-specific neutralizing antibody (NAb) response appears against the T/F virus [14,15,16]. Cross-clade neutralizing antibodies (bNAbs) are known to develop in 10–30% of HIV-1 infected individuals. These antibodies bind to the Env trimer and neutralize a broad spectrum of globally circulating HIV-1 strains [20,21,22,23]. Some recent studies have reported that while non-neutralizing antibodies (n-NAbs) trigger Fc-mediated ADCC, the Fc gamma receptors (FcgRs) play an important role in increasing the neutralizing activity of gp41-specific antibodies (2F5) but not gp120-specific antibodies. Modifications in the Fc domain to modulate its selective interaction with FcgRs can greatly influence the protective activity of bNAbs [24,25,26,27]
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