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<p>The multiple stages of the malaria parasite life cycle hampers vaccine development. Combining a pre-erythrocytic antigen with a transmission-blocking antigen would target two independent stages of the life cycle for disease control, resulting in a multistage vaccine that can prevent infection and disease transmission simultaneously. Here, we generated a self-assembled ferritin nanoparticle vaccine that simultaneously presents designed immunogens CSPj5c and 17-4 from the infection-blocking circumsporozoite and the transmission-blocking Pfs48/45 antigens. These immunogens were designed, through structure-based approaches, to retain protective epitopes and confer protection upon vaccination. Immunization with CSPj5c-17-4-ferritin nanoparticles conferred protection against challenge with transgenic sporozoites expressing <i>Plasmodium falciparum</i> CSP in mice, and purified IgGs from immunized rabbits elicited potent transmission-reducing activity. Addition of the engineered 17-4 improved the immune responses to CSPj5c and protection from sporozoite challenge. CSPj5c-17-4-ferritin is therefore a promising multistage malaria vaccine with a potential role in malaria control.</p>

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A combined designed CSP and Pfs48/45 infection and transmission blocking vaccine for malaria

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月2日

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  • Richi Gupta,
  • Thayne H. Dickey,
  • Nichole D. Salinas,
  • Palak N. Patel,
  • Rui Ma,
  • Dashuang Shi,
  • Myesha Singleton,
  • Tarik Ouahes,
  • Thao P. Pham,
  • Kazutoyo Miura,
  • Carole A. Long,
  • Lynn E. Lambert,
  • Niraj H. Tolia

摘要

The multiple stages of the malaria parasite life cycle hampers vaccine development. Combining a pre-erythrocytic antigen with a transmission-blocking antigen would target two independent stages of the life cycle for disease control, resulting in a multistage vaccine that can prevent infection and disease transmission simultaneously. Here, we generated a self-assembled ferritin nanoparticle vaccine that simultaneously presents designed immunogens CSPj5c and 17-4 from the infection-blocking circumsporozoite and the transmission-blocking Pfs48/45 antigens. These immunogens were designed, through structure-based approaches, to retain protective epitopes and confer protection upon vaccination. Immunization with CSPj5c-17-4-ferritin nanoparticles conferred protection against challenge with transgenic sporozoites expressing Plasmodium falciparum CSP in mice, and purified IgGs from immunized rabbits elicited potent transmission-reducing activity. Addition of the engineered 17-4 improved the immune responses to CSPj5c and protection from sporozoite challenge. CSPj5c-17-4-ferritin is therefore a promising multistage malaria vaccine with a potential role in malaria control.