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<p>RTS,S/AS01<sub>E</sub> is the first malaria vaccine implemented for young African children. However, it provides partial protection against <i>Plasmodium falciparum</i> (Pf) malaria, and a better understanding of the mechanisms and determinants of vaccine immunity will help develop second-generation improved vaccines. We measured IgG to vaccine target and Pf blood-stage off-target proteins before and after vaccination in 874 children aged 1–4 years in a phase 2b trial of RTS,S/AS02<sub>A</sub> in Mozambique. We found that naturally acquired PfCSP IgG levels pre-vaccination were positively associated with RTS,S immunogenicity. Increased levels of IgG to the C-terminus and NANP-repeat regions of PfCSP, and to PfMSP5 and PfMSP1 block 2, following vaccination, were significantly associated with a lower hazard of clinical malaria over 6 months. Thus, immune priming, anti-PfCSP C-terminus and off-target antibody responses contributed to malaria protection after adjusting for prior Pf exposure, and this could guide strategies for optimizing the immunogen and vaccine deployment.</p>

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Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican children

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月6日

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  • Elisa Fuentes,
  • Chenjerai Jairoce,
  • Didac Macià,
  • Leonie Mayer,
  • Jorge P. Torres-Yaguana,
  • Marta Vidal,
  • Rebeca Santano,
  • David L. Narum,
  • David Cavanagh,
  • Benoit Gamain,
  • Ross L. Coppel,
  • James G. Beeson,
  • Sheetij Dutta,
  • Jahit Sacarlal,
  • Ruth Aguilar,
  • Gemma Moncunill,
  • Carlota Dobaño

摘要

RTS,S/AS01E is the first malaria vaccine implemented for young African children. However, it provides partial protection against Plasmodium falciparum (Pf) malaria, and a better understanding of the mechanisms and determinants of vaccine immunity will help develop second-generation improved vaccines. We measured IgG to vaccine target and Pf blood-stage off-target proteins before and after vaccination in 874 children aged 1–4 years in a phase 2b trial of RTS,S/AS02A in Mozambique. We found that naturally acquired PfCSP IgG levels pre-vaccination were positively associated with RTS,S immunogenicity. Increased levels of IgG to the C-terminus and NANP-repeat regions of PfCSP, and to PfMSP5 and PfMSP1 block 2, following vaccination, were significantly associated with a lower hazard of clinical malaria over 6 months. Thus, immune priming, anti-PfCSP C-terminus and off-target antibody responses contributed to malaria protection after adjusting for prior Pf exposure, and this could guide strategies for optimizing the immunogen and vaccine deployment.