National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
米国
引用
ジャーナル: Sci Immunol / 年: 2026 タイトル: Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV V2 apex broadly neutralizing antibody development. 著者: Rumi 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 ...著者: Rumi 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 / 要旨: 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 ...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.
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