Scholarlink

<p>HIV broadly neutralizing antibodies (bnAbs) are promising reagents for prevention and therapy of disease; however, their elicitation is constrained by genetic limitations of the human B cell antigen-receptor (BCR) repertoire. Precision genome-editing offers a potential solution by enabling bnAb genes to be programmed into the BCR repertoire as <i>IgH</i>-modified B cells. Such cells can be vaccinated to elicit durable bnAb memory responses in mice; however, extending this success to non-human primates (NHPs) would be a major advance towards clinical translation. Here, we show that ex vivo reprogrammed NHP B cells can survive autologous infusion and respond to immunization, differentiating into antibody-secreting cells (ASCs) that can produce up to 1 µg/ml of a bnAb in serum following vaccination prime. Although durable transgenic memory responses were not generated, vaccination of engineered cells in secondary lymphoid organoid (SLO) cultures recapitulated transient ASC responses in vitro. These findings suggest that NHP-derived SLOs could provide a platform to optimize engineering and vaccination conditions that drive germinal center maturation of <i>IgH</i>-reprogrammed B cells in a clinically relevant NHP model, supporting the development of engineered B-cell vaccines that generate durable bnAb responses as a potential functional cure for HIV.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Vaccine elicitation of HIV broadly neutralizing antibodies from genome-edited B cells in non-human primates and derived lymphoid organoids

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月10日

查看全文
  • Mary Tenuta,
  • Morgan Bravo,
  • Alex Olson,
  • Celia L. Saney,
  • Jason Weinfurter,
  • Elana Ben-Akiva,
  • Disha Bhange,
  • Christopher A. Cottrell,
  • Logan Vosler,
  • Kimberly Weisgrau,
  • Dennis R. Burton,
  • Darrell J. Irvine,
  • William R. Schief,
  • Eva Rakasz,
  • Chester J. Joyner,
  • James E. Voss

摘要

HIV broadly neutralizing antibodies (bnAbs) are promising reagents for prevention and therapy of disease; however, their elicitation is constrained by genetic limitations of the human B cell antigen-receptor (BCR) repertoire. Precision genome-editing offers a potential solution by enabling bnAb genes to be programmed into the BCR repertoire as IgH-modified B cells. Such cells can be vaccinated to elicit durable bnAb memory responses in mice; however, extending this success to non-human primates (NHPs) would be a major advance towards clinical translation. Here, we show that ex vivo reprogrammed NHP B cells can survive autologous infusion and respond to immunization, differentiating into antibody-secreting cells (ASCs) that can produce up to 1 µg/ml of a bnAb in serum following vaccination prime. Although durable transgenic memory responses were not generated, vaccination of engineered cells in secondary lymphoid organoid (SLO) cultures recapitulated transient ASC responses in vitro. These findings suggest that NHP-derived SLOs could provide a platform to optimize engineering and vaccination conditions that drive germinal center maturation of IgH-reprogrammed B cells in a clinically relevant NHP model, supporting the development of engineered B-cell vaccines that generate durable bnAb responses as a potential functional cure for HIV.