Affiliation:
1. The Jenner Institute, University of Oxford, Oxford, United Kingdom
2. Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
Abstract
ABSTRACT
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
Plasmodium falciparum
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
P. berghei
parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-type
P. berghei
parasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed to
P. falciparum
parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidate
P. falciparum
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
P. berghei
-
P. falciparum
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
P. berghei
; when this vaccine is combined with another partially protective regimen (ChAd63-MVA PfTRAP), complete protection is induced.
Funder
UK National Institute of Health Research
Rhodes Scholarships
EC | Seventh Framework Programme
Wellcome
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
17 articles.
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