Plasmodium: Mammalian codon optimization of malaria plasmid DNA vaccines enhances antibody responses but not T cell responses nor protective immunity

Dobañoa, Carlota, Sedegah, Martha, Rogers, William O., Kumar, Sanjai, Zheng, Hong, Hoffman, Stephen L. and Doolan, Denise (2009) Plasmodium: Mammalian codon optimization of malaria plasmid DNA vaccines enhances antibody responses but not T cell responses nor protective immunity. Experimental Parasitology, 122 2: 112-123. doi:10.1016/j.exppara.2009.02.010


Author Dobañoa, Carlota
Sedegah, Martha
Rogers, William O.
Kumar, Sanjai
Zheng, Hong
Hoffman, Stephen L.
Doolan, Denise
Title Plasmodium: Mammalian codon optimization of malaria plasmid DNA vaccines enhances antibody responses but not T cell responses nor protective immunity
Journal name Experimental Parasitology   Check publisher's open access policy
ISSN 0014-4894
1090-2449
Publication date 2009-06-01
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.exppara.2009.02.010
Volume 122
Issue 2
Start page 112
End page 123
Total pages 12
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Collection year 2010
Language eng
Subject C1
92 Health
11 Medical and Health Sciences
Abstract We have evaluated the effect of mammalian codon optimization on the immunogenicity and protective efficacy of plasmid DNA vaccines encoding pre-erythrocytic stage Plasmodium falciparum and Plasmodium yoelii antigens in mice. Codon optimization significantly enhanced in vitro expression and in vivo antibody responses for P. falciparum circumsporozoite protein (PfCSP) and P. yoelii hepatocyte erythrocyte protein 17 kDa (PyHEP17) but not for P. yoelii circumsporozoite protein (PyCSP). Unexpectedly, more robust CD4+ and CD8+ T cell responses as measured by IFN-gamma ELIspot, lymphoproliferation, and cytotoxic T lymphocyte assays were noted with native as compared with codon optimization constructs. Codon optimization also failed to enhance CD8+ T cell dependent protection against P. yoelii sporozoite challenge as measured by liver-stage parasite burden. These data demonstrate that the effect of mammalian codon optimization is antigen-dependent and may not be beneficial for vaccines designed to induce T cell dependent protective immunity in this malaria model.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 21 Apr 2010, 23:40:30 EST by Jon Stekhoven on behalf of School of Medicine