Protective efficacy of an IL-12-expressing baculoviral malaria vaccine
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Interleukin-12 (IL-12) plays an important role in antigen-specific adaptive immunity against Plasmodium sporozoites, and this requirement allows for a new approach to developing an effective malaria vaccine. In this study, we examined whether IL-12 could enhance protective efficacy of a baculovirus-based malaria vaccine. For this aim, a baculoviral vector expressing murine IL-12 (mIL-12) under the control of CMV promoter (BES-mIL-12-Spider) and a baculoviral vector expressing Plasmodium falciparum circumsporozoite protein (PfCSP) with post-transcriptional regulatory element of woodchuck hepatitis virus (BDES-sPfCSP2-WPRE-Spider) were generated. BES-mIL-12-Spider produced bioactive IL-12 which activates splenocytes, resulting in induction of IFN-γ. When co-immunized with BES-mIL-12-Spider and BDES-sPfCSP2-WPRE-Spider, the mouse number for high IgG2a/IgG1 ratios and the geometric mean in this group were both increased as compared with those of the other groups, indicating a shift towards a Th1-type response following immunization with BES-mIL-12-Spider. Finally, immunization with BDES-sPfCSP2-WPRE-Spider plus BES-mIL-12-Spider had a higher protective efficacy (73%) than immunization with BDES-sPfCSP2-WPRE-Spider alone (30%) against challenge with transgenic Plasmodium berghei sporozoites expressing PfCSP. These results suggest that co-administration of IL-12 expressing baculoviral vector, instead of IL-12 cDNA, with viral-vectored vaccines provides a new feasible vaccine platform to enhance Th1-type cellular immune responses against Plasmodium parasites.
Date Issued
2017-11-24
Date Acceptance
2017-10-19
Citation
Parasite Immunology, 2017, 39 (12)
ISSN
0141-9838
Publisher
Wiley
Journal / Book Title
Parasite Immunology
Volume
39
Issue
12
Copyright Statement
This is the peer reviewed version of the following article: Iyori M, Blagborough AM, Sala KA, Nishiura H, Takagi K, Yoshida S. Protective efficacy of an IL-12-expressing baculoviral malaria vaccine. Parasite Immunol. 2017;39:e12498., which has been published in final form at https://dx.doi.org/10.1111/pim.12498. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Sponsor
Medical Research Council (MRC)
NIHR Imperial BRC Therapeutic Primer Fund
Grant Number
MR/N00227X/1
PS2843
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Parasitology
malaria
Plasmodium spp
vaccination
POSTTRANSCRIPTIONAL REGULATORY ELEMENT
PLASMODIUM-BERGHEI SPOROZOITE
EXPRESSION SYSTEM
ADAPTIVE IMMUNITY
DNA VACCINE
CHALLENGE
CELLS
MICE
TRANSMISSION
IMMUNIZATION
Publication Status
Published
Article Number
e12498