| Autor: |
Chinchilla, Magaly, Pasetti, Marcela F., Medina-Moreno, Sandra, Wang, Jin Yuan, Gomez-Duarte, Oscar G., Stout, Rick, Levine, Myron M., Galen, James E. |
| Zdroj: |
Infection and Immunity; August 2007, Vol. 75 Issue: 8 p3769-3779, 11p |
| Abstrakt: |
ABSTRACTTwo Salmonella entericaserovar Typhi strains that express and export a truncated version of Plasmodium falciparumcircumsporozoite surface protein (tCSP) fused to Salmonellaserovar Typhi cytolysin A(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 native P. 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 by Salmonellaserovar 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 with Salmonellaserovar 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 of Salmonellaserovar Typhi-PfCSP priming. Mice primed with Salmonellaserovar 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 a Salmonella-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: |
Supplemental Index |
| Externí odkaz: |
|
