Gupta Richi, Dickey Thayne H, Salinas Nichole D, Patel Palak N, Ma Rui, Shi Dashuang, Singleton Myesha, Ouahes Tarik, Pham Thao P, Miura Kazutoyo, Long Carole A, Lambert Lynn E, Tolia Niraj H
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
NPJ Vaccines. 2025 Sep 2;10(1):208. doi: 10.1038/s41541-025-01262-2.
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.
疟原虫生命周期的多个阶段阻碍了疫苗的研发。将一种前体红细胞期抗原与一种传播阻断抗原相结合,将针对生命周期中两个独立阶段进行疾病控制,从而产生一种能够同时预防感染和疾病传播的多阶段疫苗。在此,我们制备了一种自组装铁蛋白纳米颗粒疫苗,该疫苗同时展示了来自感染阻断环子孢子蛋白的设计免疫原CSPj5c和来自传播阻断Pfs48/45抗原的17-4。这些免疫原通过基于结构的方法进行设计,以保留保护性表位并在接种疫苗后提供保护。用CSPj5c-17-4-铁蛋白纳米颗粒免疫可使小鼠免受表达恶性疟原虫CSP的转基因子孢子攻击,从免疫兔中纯化的IgG引发了强大的传播减少活性。添加工程化的17-4可改善对CSPj5c的免疫反应以及对子孢子攻击的保护作用。因此,CSPj5c-17-4-铁蛋白是一种有前景的多阶段疟疾疫苗,在疟疾控制中可能发挥作用。
Cochrane Database Syst Rev. 2003
Cochrane Database Syst Rev. 2007-7-18
Lancet. 2024-2-10
Lancet Microbe. 2024-3
NPJ Vaccines. 2024-1-10