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Protective efficacy of an IL ‐12‐expressing baculoviral malaria vaccine
Author(s) -
Iyori M.,
Blagborough A. M.,
Sala K. A.,
Nishiura H.,
Takagi K.,
Yoshida S.
Publication year - 2017
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12498
Subject(s) - circumsporozoite protein , virology , parasitemia , biology , malaria , immunology , immunization , plasmodium falciparum , immune system
Summary 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 (Pf CSP ) with post‐transcriptional regulatory element of woodchuck hepatitis virus ( BDES ‐ sPfCSP 2‐ 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 ‐ sPfCSP 2‐ 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 ‐ sPfCSP 2‐ WPRE ‐Spider plus BES ‐ mIL ‐12‐Spider had a higher protective efficacy (73%) than immunization with BDES ‐ sPfCSP 2‐ 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.