Atcheson Erwan, Hill Adrian V S, Reyes-Sandoval Arturo
The Jenner Institute, University of Oxford, Oxford, UK.
Instituto Politécnico Nacional, IPN. Av. Luis Enrique Erro s/n. Unidad Adolfo López Mateos, Mexico City, Mexico.
NPJ Vaccines. 2021 Apr 1;6(1):46. doi: 10.1038/s41541-021-00302-x.
Malaria continues to be a pressing global health issue, causing nearly half a million deaths per year. An effective malaria vaccine could radically improve our ability to control and eliminate this pathogen. The most advanced malaria vaccine, RTS,S, confers only 30% protective efficacy under field conditions, and hence the search continues for improved vaccines. New antigens and formulations are always first developed at a pre-clinical level. This paper describes the development of a platform to supplement existing tools of pre-clinical malaria vaccine development, by displaying linear peptides on a virus-like particle (VLP). Peptides from PfCSP, particularly from outside the normal target of neutralizing antibodies, the central NANP repeat region, are screened for evidence of protective efficacy. One peptide, recently identified as a target of potent neutralizing antibodies and lying at the junction between the N-terminal domain and the central repeat region of PfCSP, is found to confer protective efficacy against malaria sporozoite challenge in mice when presented on the Qβ VLP. The platform is also used to explore the effects of increasing numbers of NANP unit repeats, and including a universal CD4 T-cell epitope from tetanus toxin, on immunogenicity and protective efficacy. The VLP-peptide platform is shown to be of use in screening malaria peptides for protective efficacy and answering basic vaccinology questions in a pre-clinical setting.
疟疾仍然是一个紧迫的全球健康问题，每年导致近50万人死亡。一种有效的疟疾疫苗可以从根本上提高我们控制和消除这种病原体的能力。最先进的疟疾疫苗RTS,S在现场条件下的保护效力仅为30%，因此人们仍在继续寻找改进的疫苗。新的抗原和制剂总是首先在临床前阶段开发。本文描述了一个平台的开发，该平台通过在病毒样颗粒（VLP）上展示线性肽来补充临床前疟疾疫苗开发的现有工具。筛选来自恶性疟原虫环子孢子蛋白（PfCSP）的肽，特别是来自中和抗体正常靶点之外的肽，即中央NANP重复区域，以寻找保护效力的证据。发现一种肽最近被确定为强效中和抗体的靶点，位于PfCSP的N端结构域和中央重复区域之间的交界处，当它呈现在Qβ病毒样颗粒上时，能在小鼠中赋予针对疟疾子孢子攻击的保护效力。该平台还用于探索增加NANP单位重复序列的数量以及包含来自破伤风毒素的通用CD4 T细胞表位对免疫原性和保护效力的影响。结果表明，VLP-肽平台可用于筛选具有保护效力的疟疾肽，并在临床前环境中回答基础疫苗学问题。
