This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yoshida, S.
Right arrow Articles by Matsumoto, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yoshida, S.
Right arrow Articles by Matsumoto, M.

 Previous Article  |  Next Article 

Infection and Immunity, May 2009, p. 1782-1789, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01226-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Baculovirus Dual Expression System-Based Malaria Vaccine Induces Strong Protection against Plasmodium berghei Sporozoite Challenge in Mice{triangledown} ,{dagger}

Shigeto Yoshida,1* Masanori Kawasaki,2 Norimitsu Hariguchi,2 Kuniko Hirota,2 and Makoto Matsumoto2

Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Tochigi 329-0498, Japan,1 Microbiological Research Institute, Otsuka Pharmaceutical Co. Ltd., Tokushima 771-0192, Japan2

Received 7 October 2008/ Returned for modification 12 November 2008/ Accepted 6 February 2009

We have previously shown that a recombinant baculovirus that displays Plasmodium berghei circumsporozoite protein (PbCSP), a homolog of the leading human malaria vaccine candidate, on the viral envelope protected 60% of mice against P. berghei infection. Here, we describe a second-generation baculovirus vaccine based on the "baculovirus dual expression system," which drives PbCSP expression by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammal-derived cytomegalovirus promoters. The baculovirus-based PbCSP vaccine not only displayed PbCSP on the viral envelope but also expressed PbCSP upon transduction of mammalian cells. Immunization with the baculovirus-based PbCSP vaccine elicited high PbCSP-specific antibody titers (predominantly immunoglobulin G1 [IgG1] and IgG2a) and PbCSP-specific CD8+ T-cell responses without extraneous immunological adjuvants in mice, indicating that there was induction of both Th1 and Th2 responses (a mixed Th1/Th2 response). Importantly, upon intramuscular inoculation, the baculovirus-based PbCSP vaccine conferred complete protection against sporozoite challenge. Thus, the baculovirus-based PbCSP vaccine induced strong protective immune responses against preerythrocytic parasites. These results introduce a novel concept for the baculovirus dual expression system that functions as both a subunit vaccine and a DNA vaccine and offer a promising new alternative to current human vaccine delivery platforms.

* Corresponding author. Mailing address: Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. Phone: 81-285-58-7339. Fax: 81-285-44-6489. E-mail: shigeto{at}jichi.ac.jp

{triangledown} Published ahead of print on 17 February 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: W. A. Petri, Jr.

Infection and Immunity, May 2009, p. 1782-1789, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01226-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»