Enhanced Immunity toPlasmodium falciparumCircumsporozoite Protein (PfCSP) by UsingSalmonella entericaSerovar Typhi Expressing PfCSP and a PfCSP-Encoding DNA Vaccine in a Heterologous Prime-Boost Strategy
| Autor: | Rick Stout, James E. Galen, Marcela F. Pasetti, Myron M. Levine, Magaly Chinchilla, Jin Yuan Wang, Oscar G. Gómez-Duarte, Sandra Medina-Moreno |
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| Rok vydání: | 2007 |
| Předmět: |
Salmonella
Recombinant Fusion Proteins Genetic Vectors Molecular Sequence Data Plasmodium falciparum Immunology Immunization Secondary Protozoan Proteins Antibodies Protozoan Salmonella typhi medicine.disease_cause complex mixtures Microbiology DNA vaccination Epitopes Hemolysin Proteins Interferon-gamma Mice Plasmid Bacterial Proteins Malaria Vaccines Vaccines DNA medicine Animals Amino Acid Sequence Immunity Mucosal Cells Cultured Mice Inbred BALB C biology Malaria vaccine Immunogenicity biology.organism_classification Virology Circumsporozoite protein Infectious Diseases Models Animal Microbial Immunity and Vaccines Leukocytes Mononuclear Female Parasitology |
| Zdroj: | Infection and Immunity. 75:3769-3779 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00356-07 |
| Popis: | TwoSalmonella entericaserovar Typhi strains that express and export a truncated version ofPlasmodium falciparumcircumsporozoite surface protein (tCSP) fused toSalmonellaserovar TyphicytolysinA(ClyA) were constructed as a first step in the development of a preerythrocytic malaria vaccine. Synthetic codon-optimized genes (t-csp1and t-csp2), containing immunodominant B- and T-cell epitopes present in nativeP. falciparumcircumsporozoite surface protein (PfCSP), were fused in frame to the carboxyl terminus of the ClyA gene (clyA::t-csp) in genetically stabilized expression plasmids. Expression and export of ClyA-tCSP1 and ClyA-tCSP2 bySalmonellaserovar Typhi vaccine strain CVD 908-htrAwere demonstrated by immunoblotting of whole-cell lysates and culture supernatants. The immunogenicity of these constructs was evaluated using a “heterologous prime-boost” approach consisting of mucosal priming withSalmonellaserovar Typhi expressing ClyA-tCSP1 and ClyA-tCSP2, followed by parenteral boosting with PfCSP DNA vaccines pVR2510 and pVR2571. Mice primed intranasally on days 0 and 28 with CVD 908-htrA(pSEC10tcsp2) and boosted intradermally on day 56 with PfCSP DNA vaccine pVR2571 induced high titers of serum NANP immunoglobulin G (IgG) (predominantly IgG2a); no serological responses to DNA vaccination were observed in the absence ofSalmonellaserovar Typhi-PfCSP priming. Mice primed withSalmonellaserovar Typhi expressing tCSP2 and boosted with PfCSP DNA also developed high frequencies of gamma interferon-secreting cells, which surpassed those produced by PfCSP DNA in the absence of priming. A prime-boost regimen consisting of mucosal delivery of PfCSP exported from aSalmonella-based live-vector vaccine followed by a parenteral PfCSP DNA boosting is a promising strategy for the development of a live-vector-based malaria vaccine. |
| Databáze: | OpenAIRE |
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