Dieter Mielke, Gama Bandawe, Justin Pollara, Melissa-Rose Abrahams, Tinashe Nyanhete, Penny L. Moore, Ruwayhida Thebus, Nicole L. Yates, John C. Kappes, Christina Ochsenbauer, Nigel Garrett, Salim Abdool Karim, Georgia D. Tomaras, David Montefiori, Lynn Morris, Guido Ferrari, Carolyn Williamson
Abstract
Both neutralization and antibody-dependent cellular cytotoxicity (ADCC) may be required for effective protection against HIV-1 infection. While there is extensive information on the targets of early neutralizing antibody (nAb) responses, much less is known about the targets of ADCC responses, which are more difficult to characterize. In four individuals recruited during acute HIV-infection, ADCC responses were detected 3-7 weeks prior to nAb responses. To determine the relative influence of ADCC and nAb responses on virus evolution, we performed an in-depth investigation of one individual (CAP63) who showed the highest nAb and ADCC responses. Both nAbs and ADCC antibodies targeted the V4 region of the Env, although there were some differences in epitope recognition. We identified accelerated viral evolution in this region concurrent with emergence of nAb activity, but not ADCC activity. Deep sequencing demonstrated that most nAb escape mutations were strongly selected for, however one nAb escape mutation that rendered the virus highly susceptible to autologous ADCC responses, was suppressed despite not affecting viral fitness. This escape mutation also rendered the virus more sensitive to autologous responses, as well as monoclonal antibodies targeting CD4-induced epitopes, compared to the wildtype virus. In conclusion, ADCC responses and nAbs in donor CAP63 recognized overlapping but unique epitopes in the V4 region, and while ADCC activity was present prior to nAbs, it did not drive viral evolution during this time. However, ADCC responses may select against nAb escape pathways that expose other common ADCC epitopes thereby restricting viral replication and expansion.
Pharmacology, Toxicology and Pharmaceutical Science
2
4%
Engineering
2
4%
Other
3
5%
Unknown
18
32%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 January 2020.
All research outputs
#17,284,203
of 26,163,973 outputs
Outputs from Frontiers in immunology
#18,956
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Outputs of similar age
#292,764
of 484,001 outputs
Outputs of similar age from Frontiers in immunology
#408
of 578 outputs
Altmetric has tracked 26,163,973 research outputs across all sources so far. This one is in the 31st percentile – i.e., 31% of other outputs scored the same or lower than it.
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