Immunization with a circumsporozoite epitope fused to Bordetella pertussis adenylate cyclase in conjunction with cytotoxic T-lymphocyte-associated antigen 4 blockade confers protection against Plasmodium berghei liver-stage malaria

Tartz, Susanne; Kamanova, Jana; Simsova, Marcela; Sebo, Peter; Bolte, Stefanie; Heussler, Volker; Fleischer, Bernhard; Jacobs, Thomas (2006). Immunization with a circumsporozoite epitope fused to Bordetella pertussis adenylate cyclase in conjunction with cytotoxic T-lymphocyte-associated antigen 4 blockade confers protection against Plasmodium berghei liver-stage malaria. Infection and immunity, 74(4), pp. 2277-2285. American Society for Microbiology 10.1128/IAI.74.4.2277-2285.2006

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The adenylate cyclase toxoid (ACT) of Bordetella pertussis is capable of delivering its N-terminal catalytic domain into the cytosol of CD11b-expressing professional antigen-presenting cells such as myeloid dendritic cells. This allows delivery of CD8+ T-cell epitopes to the major histocompatibility complex (MHC) class I presentation pathway. Recombinant detoxified ACT containing an epitope of the Plasmodium berghei circumsporozoite protein (CSP), indeed, induced a specific CD8+ T-cell response in immunized mice after a single application, as detected by MHC multimer staining and gamma interferon (IFN-gamma) ELISPOT assay. This CSP-specific response could be significantly enhanced by prime-boost immunization with recombinant ACT in combination with anti-CTLA-4 during the boost immunization. This increased response was accompanied by complete protection in a number of mice after a challenge with P. berghei sporozoites. Transient blockade of CTLA-4 may overcome negative regulation and hence provide a strategy to enhance the efficacy of a vaccine by amplifying the number of responding T cells.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology > Malaria
08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Heussler, Volker

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0019-9567

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Volker Heussler

Date Deposited:

06 Jul 2016 11:31

Last Modified:

07 Jul 2016 04:34

Publisher DOI:

10.1128/IAI.74.4.2277-2285.2006

PubMed ID:

16552058

BORIS DOI:

10.7892/boris.84076

URI:

https://boris.unibe.ch/id/eprint/84076

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