Envelope characteristics in individuals who developed neutralizing antibodies targeting different epitopes in HIV-1 subtype C infection

Long-term and low-level envelope C2V3 stimulation from highly diverse virus isolates leads to frequent development of broad and elite antibody neutralization in HIV-1 infected individuals

“…We found that the majority (56%) of the patients in our cohort developed cross, broad, or elite neutralizing responses. These results far exceed those from previous cohort studies in sub-Saharan Africa 3,63,79,84,85 . For example, Beirnaert et al found 10.6% broad neutralizers in Cameroon 85 and Landais et al found about 15% broad neutralizers in a cohort of HIV-1 infected patients from Eastern and South Africa 3 .…”

“…However, elite neutralizers exhibited far less variability and lower number of sites under selective pressure in V3 and C3 relative to weak or low neutralizers. The convergence of the viral swarm to a few resistant strains provides convincing evidence for the crucial role of V3-and C3-directed bNAbs in controlling HIV-1 replication and diversification in these patients 35,61,84,99 .…”

“…Viral type and subtype as well as the nature of the epitope target on the viral envelope impact the antibody maturation process as seen by the frequency of elicitation 61,93 and epitope specificity of bnAbs 2,50,76 . Differences in envelope structure and epitope exposure, length of variable loops, type of V3 motifs, N-glycosylation patterns, and conservation of key sites have helped to explain why certain HIV-1 subtypes like subtype C are better at promoting the elicitation of neutralizing antibodies 2,3,50,61,76,84,95 . In line with these studies, we found that infection with subtype C viruses was associated with enhanced neutralization breadth and potency.…”

“…In line with these studies, we found that infection with subtype C viruses was associated with enhanced neutralization breadth and potency. In general, subtype C infected individuals have shown a bias to V2-glycan directed antibody responses, and subtype C envelope from transmitted viruses have been less prone to neutralization by V3-directed antibodies due to the absence of the N332-glycan in the C3 region 2,3,76,84,96,97,98 . This was not the case in our study as most top neutralizers had V3-directed antibodies that were able to neutralize the subtype C isolates from the virus panel, and the N301 and N332 glycans defining the V3-glycan supersite were highly conserved in the patient's isolates.…”

Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time

“…We were unable to draw the specificity of broadly neutralizing antibodies from this donor. Nevertheless, the specificities of bNAbs could be indicated by sequence analysis that revealed immune pressure ( Ndlovu et al., 2020 ). To further understand the relationship between sensitivity of viral variants to bNAbs and evolution of Env, we drew the sequence LOGOs of AA signatures of 10E8 and VRC01 in the 4 sequential samples, using HIV-1 antibody-binding sites and the mutation information summarized in the HIV Molecular Immunology Database ( ), as well as results found in the literature ( Bricault et al., 2019 ) ( Figure 5 ).…”