Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine

<jats:title>ABSTRACT</jats:title> <jats:p> Efforts are under way to improve the efficacy of subunit malaria vaccines through assessments of new adjuvants, vaccination platforms, and antigens. In this study, we further assessed the <jats:named-content content-type="genus-species">Plasmodium falciparum</jats:named-content> antigen upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric <jats:named-content content-type="genus-species">P. berghei</jats:named-content> parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-type <jats:named-content content-type="genus-species">P. berghei</jats:named-content> parasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed to <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidate <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> thrombospondin-related adhesion protein (PfTRAP) expressed in the ChAd63-MVA system, there was no significant change in immunogenicity to either vaccine. However, when mice were challenged with double chimeric <jats:named-content content-type="genus-species">P. berghei</jats:named-content> - <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was evident only when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild-type <jats:named-content content-type="genus-species">P. berghei</jats:named-content> ; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced. </jats:p>