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

Dobaño, Carlota, Sedegah, Martha, Rogers, William O., Kumar, Sanjai, Zheng, Hong, Hoffman, Stephen L., and Doolan, Denise L. (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). pp. 112-123.

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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-γ 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.

Item ID: 42734
Item Type: Article (Refereed Research - C1)
Keywords: malaria; Plasmodium yoelii; Plasmodium falciparum; protozoa; DNA vaccine; codon optimization; synthetic genes; native genes; T cells; antibodies
ISSN: 1090-2449
Funders: United States Army Medical Research and Materiel Command (USAMRMC), Naval Medical Research Centre (NMRC)
Projects and Grants: USAMRMC 6102A.00101.BFX, USAMRMC 61102A.S13.F.A0009, USAMRMC 62787A.977.A0238
Date Deposited: 24 Mar 2016 00:04
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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