Scholarlink

<p>Repetitive display of the major repeats of the <i>Plasmodium falciparum</i> circumsporozoite protein (PfCSP) is the basis for two WHO-recommended vaccines: RTS,S/AS01 and R21/Matrix-M. Recently, however, the CIS43 monoclonal antibody that preferentially targets the junctional region of PfCSP has been shown to be highly protective in humans, highlighting its junctional epitope as a key vaccine target. Here, we develop a vaccine based on tandem repeats of the junctional epitope displayed on a self-assembling nanoparticle and compare this CIS43-based junctional vaccine alone or in combination with the benchmark R21 vaccine, using both B cell analysis and monoclonal antibody isolation to define targeting of the immune response. Comparable reduction in liver burden was observed following vaccination with the best junctional vaccine and R21 at a dose of 1 μg. At a dose of 0.25 μg, a modest reduction of malaria liver burden with the junctional vaccine was observed compared to R21. Further, combining the junctional and R21 vaccines did not yield substantial improvement, although a modest trend was observed. While the R21 vaccine elicited antibodies primarily against the major repeats, the junctional vaccine elicited antibodies against both junctional and major repeat regions. In vivo B cell analysis and isolation of monoclonal antibodies confirmed differences in vaccine-induced antibody specificities. Altogether, these data suggest the nanoparticle-formatted tandem-repeated CIS43-junctional vaccine to be a promising approach to broaden immunity against malaria, either as a standalone intervention or in combination with R21.</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

Protective immunity against malaria by a nanoparticle CIS43-based junctional vaccine alone or in combination with R21

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月27日

查看全文
  • Prabhanshu Tripathi,
  • Ja-Hyun Koo,
  • Xuejun Chen,
  • Lais Da Silva Pereira,
  • Marlon Dillon,
  • Baoshan Zhang,
  • Mariah Lofgren,
  • Katelyn T. Nguyen,
  • I-Ting Teng,
  • Brian Bonilla,
  • Sarah Kerscher,
  • Wing-Pui Kong,
  • Amy R. Henry,
  • Tyler Stephens,
  • Yaroslav Tsybovsky,
  • Stephanie R. Weldon,
  • Daniel C. Douek,
  • Theodore C. Pierson,
  • Facundo D. Batista,
  • Azza H. Idris,
  • Robert A. Seder,
  • Peter D. Kwong,
  • Tongqing Zhou

摘要

Repetitive display of the major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) is the basis for two WHO-recommended vaccines: RTS,S/AS01 and R21/Matrix-M. Recently, however, the CIS43 monoclonal antibody that preferentially targets the junctional region of PfCSP has been shown to be highly protective in humans, highlighting its junctional epitope as a key vaccine target. Here, we develop a vaccine based on tandem repeats of the junctional epitope displayed on a self-assembling nanoparticle and compare this CIS43-based junctional vaccine alone or in combination with the benchmark R21 vaccine, using both B cell analysis and monoclonal antibody isolation to define targeting of the immune response. Comparable reduction in liver burden was observed following vaccination with the best junctional vaccine and R21 at a dose of 1 μg. At a dose of 0.25 μg, a modest reduction of malaria liver burden with the junctional vaccine was observed compared to R21. Further, combining the junctional and R21 vaccines did not yield substantial improvement, although a modest trend was observed. While the R21 vaccine elicited antibodies primarily against the major repeats, the junctional vaccine elicited antibodies against both junctional and major repeat regions. In vivo B cell analysis and isolation of monoclonal antibodies confirmed differences in vaccine-induced antibody specificities. Altogether, these data suggest the nanoparticle-formatted tandem-repeated CIS43-junctional vaccine to be a promising approach to broaden immunity against malaria, either as a standalone intervention or in combination with R21.