| Summary: | <p>To screen for additional vaccine candidate antigens of <em>Plasmodium</em> pre-erythrocytic stages, fourteen <em>P</em>. <em>falciparum</em> proteins were selected based on expression in sporozoites or their role in establishment of hepatocyte infection. For preclinical evaluation of immunogenicity of these proteins in mice, chimeric <em>P</em>. <em>berghei</em> sporozoites were created that express the <em>P</em>. <em>falciparum</em> proteins in sporozoites as an additional copy gene under control of the <em>uis4</em> gene promoter. All fourteen chimeric parasites produced sporozoites but sporozoites of eight lines failed to establish a liver infection, indicating a negative impact of these <em>P</em>. <em>falciparum</em> proteins on sporozoite infectivity. Immunogenicity of the other six proteins (SPELD, ETRAMP10.3, SIAP2, SPATR, HT, RPL3) was analyzed by immunization of inbred BALB/c and outbred CD-1 mice with viral-vectored (ChAd63 or ChAdOx1, MVA) vaccines, followed by challenge with chimeric sporozoites. Protective immunogenicity was determined by analyzing parasite liver load and prepatent period of blood stage infection after challenge. Of the six proteins only SPELD immunized mice showed partial protection. We discuss both the low protective immunogenicity of these proteins in the chimeric rodent malaria challenge model and the negative effect on <em>P</em>. <em>berghei</em> sporozoite infectivity of several <em>P</em>. <em>falciparum</em> proteins expressed in the chimeric sporozoites.</p>
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