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TitleEnv-antibody coevolution identifies B cell priming as the principal bottleneck to HIV V2 apex broadly neutralizing antibody development.
Journal, issue, pagesSci Immunol, Vol. 11, Issue 116, Page eadz3933, Year 2026
Publish dateFeb 13, 2026
AuthorsRumi Habib / Ryan S Roark / Hui Li / Andrew Jesse Connell / Michael P Hogarty / Kshitij Wagh / Shuyi Wang / Lorie Marchitto / Ashwin N Skelly / John W Carey / Kirsten J Sowers / Kasirajan Ayyanathan / Samantha J Plante / Frederic Bibollet-Ruche / Younghoon Park / Colby J Agostino / Ajay Singh / Christian L Martella / Emily Lewis / Juliette M Rando / Neha Chohan / Jinery Lora / Wenge Ding / Mary S Campion / Chengyan Zhao / Weimin Liu / Yingying Li / Xuduo Li / Bo Liang / Rohan Roy Chowdhury / Khaled Amereh / Elizabeth Van Itallie / Zizhang Sheng / Amrit R Ghosh / Katharine J Bar / Wilton B Williams / Kevin Wiehe / Kevin O Saunders / Robert J Edwards / Derek W Cain / Mark G Lewis / Facundo D Batista / Dennis R Burton / Raiees Andrabi / Daniel W Kulp / Barton F Haynes / Bette Korber / Lawrence Shapiro / Peter D Kwong / Beatrice H Hahn / George M Shaw /
PubMed AbstractBroadly neutralizing antibodies (bNAbs) are rarely elicited during HIV-1 infection. To identify obstacles to bNAb development, we longitudinally studied 122 rhesus macaques infected by 1 of 16 ...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 1 of 16 different simian-human immunodeficiency viruses (SHIVs). We identified the V2 apex region of the envelope (Env) 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 a primary obstacle to V2 apex bNAb elicitation in SHIV-infected macaques and identify specific HIV-1 Envs to advance as vaccine platforms.
External linksSci Immunol / PubMed:41686912
MethodsEM (single particle)
Resolution3.6 Å
Structure data

70613

9omg

EMDB-70613: Cryo-EM structure of rhesus antibody V033-Int1 in complex with HIV Env trimer Q23.17 MD39
PDB-9omg: Cryo-EM structure of rhesus antibody V033-a.I1 in complex with HIV Env trimer Q23.17 MD39
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • macaca mulatta (Rhesus monkey)
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Neutralizing antibody / HIV-1 V2 apex / SHIV-elicited / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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