Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals.

Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine

Evolution of Neutralization Response in HIV-1 Subtype C-Infected Individuals Exhibiting Broad Cross-Clade Neutralization of HIV-1 Strains

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/mm(3)) and continued to remain ART-naive 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

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<p>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.</p