Rausch Kelly M, Barnafo Emma K, Lambert Lynn E, Muratova Olga, Gorres J Patrick, Anderson Charles, Narum David L, Wu Yimin, Morrison Robert D, Zaidi Irfan, Duffy Patrick E
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
iScience. 2023 Jun 22;26(7):107192. doi: 10.1016/j.isci.2023.107192. eCollection 2023 Jul 21.
Malaria transmission-blocking vaccine candidates Pfs25-EPA and Pfs230D1-EPA target sexual stage development of parasites in the mosquito host, thereby reducing mosquito infectivity. When formulated on Alhydrogel, Pfs25-EPA has demonstrated safety and immunogenicity in a phase 1 field trial, while Pfs230D1-EPA has shown superior activity to Pfs25-EPA in a phase 1 US trial and has entered phase 2 field trials. Development continues to enhance immunogenicity of these candidates toward producing a vaccine to reduce malaria transmission (VRMT) with both pre-erythrocytic (, anti-infection) and transmission-blocking components. GSK Adjuvant Systems have demonstrated successful potency in pre-erythrocytic vaccine trials and might offer a common platform for VRMT development. Here, we describe preclinical evaluations of Pfs25-EPA and Pfs230D1-EPA nanoparticles with GSK platforms. Formulations were stable after a series of assessments and induced superior antibody titers and functional activity in CD-1 mice, compared to Alhydrogel formulations of the same antigens.
疟疾传播阻断候选疫苗Pfs25-EPA和Pfs230D1-EPA靶向蚊子宿主体内疟原虫的有性阶段发育，从而降低蚊子的感染性。当与氢氧化铝佐剂一起配制时，Pfs25-EPA在1期现场试验中已证明其安全性和免疫原性，而Pfs230D1-EPA在美国的1期试验中显示出比Pfs25-EPA更强的活性，现已进入2期现场试验。研发工作仍在继续，以增强这些候选疫苗的免疫原性，从而生产出一种同时具备红细胞前期（抗感染）和传播阻断成分的疟疾传播减少疫苗（VRMT）。葛兰素史克佐剂系统在红细胞前期疫苗试验中已证明具有成功的效力，可能为VRMT的研发提供一个通用平台。在此，我们描述了使用葛兰素史克平台对Pfs25-EPA和Pfs230D1-EPA纳米颗粒进行的临床前评估。与相同抗原的氢氧化铝佐剂配方相比，经过一系列评估后，这些配方稳定，并且在CD-1小鼠中诱导产生了更高的抗体滴度和功能活性。
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