Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV-1 V2 apex broadly neutralizing antibody development
preprint
OA: closed
Abstract
Broadly neutralizing antibodies (bNAbs) are rarely elicited during HIV-1 infection. To identify obstacles to bNAb development, we longitudinally studied 122 rhesus macaques infected by one of 16 different simian-human immunodeficiency viruses (SHIVs). We identified V2 apex as the most common bNAb target and a subset of Envs that preferentially elicited these antibodies. In 10 macaques, we delineated Env-antibody coevolution from B cell priming to bNAb development. Antibody phylogenies revealed permissive developmental pathways guided by evolving Envs that contained few mutations in or near the V2 apex C-strand, which were a sensitive indicator of apex-targeted responses. The absence of such mutations reflected a failure in bNAb priming. These results indicate that efficiency of B cell priming, and not complexities in Env-guided affinity maturation, is the primary obstacle to V2 apex bNAb elicitation in SHIV-infected macaques and identify specific HIV-1 Envs to advance as novel vaccine platforms. One sentence summary B cell priming is the primary bottleneck to HIV-1 V2 apex bNAb elicitation.
Full text
2,034 characters
· extracted from
oa-doi-fallback
· click to expand
Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV-1 V2 apex broadly neutralizing antibody development
Abstract
Broadly neutralizing antibodies (bNAbs) are rarely elicited during HIV-1 infection. To identify obstacles to bNAb development, we longitudinally studied 122 rhesus macaques infected by one of 16 different simian-human immunodeficiency viruses (SHIVs). We identified V2 apex as the most common bNAb target and a subset of Envs that preferentially elicited these antibodies. In 10 macaques, we delineated Env-antibody coevolution from B cell priming to bNAb development. Antibody phylogenies revealed permissive developmental pathways guided by evolving Envs that contained few mutations in or near the V2 apex C-strand, which were a sensitive indicator of apex-targeted responses. The absence of such mutations reflected a failure in bNAb priming. These results indicate that efficiency of B cell priming, and not complexities in Env-guided affinity maturation, is the primary obstacle to V2 apex bNAb elicitation in SHIV-infected macaques and identify specific HIV-1 Envs to advance as novel vaccine platforms.
One sentence summary B cell priming is the primary bottleneck to HIV-1 V2 apex bNAb elicitation.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Changes throughout text and figures incorporating new data
Funder Information Declared
Subject Area
- Biochemistry (17703)
- Bioengineering (13897)
- Bioinformatics (41960)
- Biophysics (21458)
- Cancer Biology (18597)
- Cell Biology (25524)
- Clinical Trials (138)
- Developmental Biology (13381)
- Ecology (19905)
- Epidemiology (2067)
- Evolutionary Biology (24325)
- Genetics (15612)
- Genomics (22512)
- Immunology (17738)
- Microbiology (40421)
- Molecular Biology (17187)
- Neuroscience (88627)
- Paleontology (667)
- Pathology (2834)
- Pharmacology and Toxicology (4825)
- Physiology (7645)
- Plant Biology (15158)
- Synthetic Biology (4302)
- Systems Biology (9825)
- Zoology (2271)
Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.
My notes (saved in your browser only)
Ask this paper
Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works
Citation neighborhood (no data yet)
We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.
Source provenance
- europepmc
- last seen: 2026-05-20T01:45:00.602351+00:00