Construction and immunogenicity in mice of attenuated Salmonella typhi expressing Plasmodium falciparum merozoite surface protein 1 (MSP-1) fused to tetanus toxin fragment C

Shaoguang Wu, Magda Beier, Marcelo B. Sztein, James Galen, Thames Pickett, Anthony A. Holder, Oscar G. Gómez-Duarte, Myron M. Levine

Research output: Contribution to journalArticlepeer-review

Abstract

One strategy to develop a multi-antigen malaria vaccine is to employ live vectors to carry putative protective Plasmodium falciparum antigens to the immune system. The 19 kDa carboxyl terminus of P. falciparum merozoite surface protein 1 (MSP-1), which is essential for erythrocyte invasion and is a leading antigen for inclusion in a multivalent malaria vaccine, was genetically fused to fragment C of tetanus toxin and expressed within attenuated Salmonella typhi CVD 908. Under conditions in the bacterial cytoplasm, the fragment C-MSP-1 fusion did not form the epidermal growth factor (EGF)-like domains of MSP-1; monoclonal antibodies failed to recognize these conformational domains in immunoblots of non-denatured protein extracted from live vector sonicates. The MSP-1 was nevertheless immunogenic. One month following intranasal immunization of BALB/c mice with the live vector construct, four out of five mice exhibited ≥ four-fold rises in anti- MSP-1 by ELISA (GMT = 211); a single intranasal booster raised titers further (GMT = 1280). Post-immunization sera recognized native MSP-1 on merozoites as determined by indirect immunofluorescence. These data encourage efforts to optimize MSP-1 expression in S. typhi (e.g. as a secreted protein), so that the EGF-like epitopes, presumably necessary for stimulating protective antibodies, can form. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)125-135
Number of pages11
JournalJournal of Biotechnology
Volume83
Issue number1-2
DOIs
StatePublished - Sep 29 2000
Externally publishedYes

Keywords

  • Malaria
  • Merozoites
  • Salmonella typhi
  • Vaccines

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Fingerprint

Dive into the research topics of 'Construction and immunogenicity in mice of attenuated Salmonella typhi expressing Plasmodium falciparum merozoite surface protein 1 (MSP-1) fused to tetanus toxin fragment C'. Together they form a unique fingerprint.

Cite this