Assessment of the Plasmodium falciparum pre-erythrocytic antigen UIS3 as a potential candidate for a malaria vaccine
Longley, RJ; Halbroth, BR; Salman, AM; Ewer, KJ; Hodgson, SH; Janse, CJ; Khan, SM; Hill, AV; Spencer, AJ
Infection and Immunity
Efforts are currently underway to improve the efficacy of sub-unit malaria vaccines through assessment of new adjuvants, vaccination platforms and antigens. In this study, we further assess the antigen P. falciparum (Pf) 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 P. berghei (Pb) parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild type Pb parasites. We also show that PfUIS3-specific cellular memory responses can be recalled in human volunteers exposed to Pf parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was co-administered with the vaccine candidate ChAd63-MVA Pf thrombospondin-related adhesion protein (TRAP), there was no significant change in immunogenicity to either vaccine. However, when these mice were challenged with double chimeric Pb-Pf parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was only evident 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 parasitaemia across mouse strains and against chimeric parasites expressing PfUIS3 as well as wild type Pb; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced.