Abstract
Dissecting antibody specificities in the plasma of HIV-1 infected individuals that develop broadly neutralizing antibodies (bNAbs) is likely to provide useful information for refining target epitopes for vaccine design. Several studies have reported CD4-binding site (CD4bs) antibodies as neutralization determinants in the plasma of subtype B-infected individuals; however there is little information on the prevalence of CD4bs specificities in HIV-infected individuals in India. Here, we report on the presence of CD4bs antibodies and their contribution to virus neutralization in the plasma from a cohort of HIV-1 infected Indian individuals. Plasma from 11 of the 140 HIV-1 infected individuals (7.9%) studied here exhibited cross-neutralization activity against a panel of subtype B and C viruses. Analyses of these 11 plasma samples for the presence of CD4bs antibodies using two CD4bs-selective probes (antigenically resurfaced HXB2gp120 core protein RSC3 and hyperglycosylated JRFLgp120 mutant ΔN2mCHO) revealed that five (AIIMS 617, 619, 627, 642, 660) contained RSC3-reactive plasma antibodies and only one (AIIMS 660) contained ΔN2mCHO-reactive antibodies. Plasma antibody depletion and competition experiments confirmed that the neutralizing activity in the AIIMS 660 plasma was dependent on CD4bs antibodies. To the best of our knowledge, this is the first study to report specifically on the presence of CD4bs antibodies in the plasma of a cohort of HIV-1 infected Indian donors. The identification of CD4bs dependent neutralizing antibodies in an HIV-1 infected Indian donor is a salient finding of this study and is supportive of ongoing efforts to induce similar antibodies by immunization.
Highlights
Development of an effective vaccine against human immunodeficiency virus (HIV-1) continues to be a global challenge
It is well known that all the neutralizing antibody (NAb) response in HIV-1 infected individuals is directed against the envelope glycoprotein of HIV-1 [1,2,3,4]
Half of the plasma samples were tested against a panel of 22 pseudoviruses (17 subtype C and 5 subtype B; Table 1), the other half were checked against a panel of 13 pseudoviruses (6 subtype C, 6 subtype B and 1 subtype A) (Table 2)
Summary
Development of an effective vaccine against human immunodeficiency virus (HIV-1) continues to be a global challenge. Over the last two decades, and in the last 5–7 years with the advent of high throughput techniques, a sizeable number of bNAbs with different specificities have been isolated from HIV-1 infected individuals These include specificities to the CD4bs, exemplified by antibodies b12, 3BNC117 and the VRC01 family of antibodies [16,17,18,19,20], glycan dependent trimer specific epitopes spanning the V2V3 region, recognized by antibody PG9 and the CH01 and PGT145 antibody families [21,22,23], glycan dependent epitopes at the base of the V3 region, represented by antibody 2G12 and the PGT121 and PGT128 antibody families [24,25,26,27], quaternary glycan dependent epitopes that span the gp120/gp interface, exemplified by antibody 35O22 and the PGT151 family of antibodies [28,29,30], and the membrane-proximal external region of gp, targeted by antibodies 2F5, 4E10 and 10E8 [31,32,33,34,35,36]
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