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

• Published in: Infection and immunity Vol. 85; no. 3
• Main Authors: Longley, Rhea J, Halbroth, Benedict R, Salman, Ahmed M, Ewer, Katie J, Hodgson, Susanne H, Janse, Chris J, Khan, Shahid M, Hill, Adrian V S, Spencer, Alexandra J
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.03.2017
• Subjects: Animals; Antibodies, Protozoan - immunology; Antigens, Protozoan - immunology; Disease Models, Animal; Female; Humans; Immunization; Immunologic Memory; Malaria Vaccines - genetics; Malaria Vaccines - immunology; Malaria, Falciparum - immunology; Malaria, Falciparum - prevention & control; Membrane Proteins - genetics; Membrane Proteins - immunology; Mice; Microbial Immunity and Vaccines; Plasmodium falciparum - immunology; Protozoan Proteins - genetics; Protozoan Proteins - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Plasmodium; UIS3; synergy; sterile protection; vaccines; liver stage; malaria
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.00641-16

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 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 parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-type parasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed to parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidate 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 - 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 ; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced.