AUTHOR=Hon Calvin , Friesen Johannes , Ingmundson Alyssa , Scheppan Diana , Hafalla Julius C. R. , Müller Katja , Matuschewski Kai 

TITLE=Conservation of S20 as an Ineffective and Disposable IFNγ-Inducing Determinant of Plasmodium Sporozoites Indicates Diversion of Cellular Immunity

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.703804

DOI=10.3389/fmicb.2021.703804

ISSN=1664-302X

ABSTRACT=<p>Despite many decades of research to develop a malaria vaccine, only one vaccine candidate has been explored in pivotal phase III clinical trials. This candidate subunit vaccine consists of a portion of a single <italic>Plasmodium</italic> antigen, circumsporozoite protein (CSP). This antigen was initially identified in the murine malaria model and shown to contain an immunodominant and protective CD8<sup>+</sup> T cell epitope specific to the H-2K<sup><italic>d</italic></sup> (BALB/c)-restricted genetic background. A high-content screen for CD8<sup>+</sup> epitopes in the H2K<sup><italic>b</italic></sup>/D<sup><italic>b</italic></sup> (C57BL/6)-restricted genetic background, identified two distinct dominant epitopes. In this study, we present a characterization of one corresponding antigen, the <italic>Plasmodium</italic> sporozoite-specific protein <italic>S20</italic>. <italic>Plasmodium berghei S20</italic> knockout sporozoites and liver stages developed normally <italic>in vitro</italic> and <italic>in vivo</italic>. This potent infectivity of <italic>s20</italic>(-) sporozoites permitted comparative analysis of knockout and wild-type parasites in cell-based vaccination. Protective immunity of irradiation-arrested <italic>s20</italic>(-) sporozoites in single, double and triple immunizations was similar to irradiated unaltered sporozoites in homologous challenge experiments. These findings demonstrate the presence of an immunogenic <italic>Plasmodium</italic> pre-erythrocytic determinant, which is not essential for eliciting protection. Although <italic>S20</italic> is not needed for colonization of the mammalian host and for initiation of a blood infection, it is conserved amongst <italic>Plasmodium</italic> species. Malarial parasites express conserved, immunogenic proteins that are not required to establish infection but might play potential roles in diverting cellular immune responses.</p>