title: Salmonella typhi vaccine strain CVD 908 expressing the circumsporozoite protein of Plasmodium falciparum: strain construction and safety and immunogenicity in humans.
abstract: rcsp, encoding amino acids 21-398 of Plasmodium falciparum circumsporozoite protein (CSP), under control of tacP was integrated into the chromosomal delta aroC locus of attenuated delta aroC, delta aroD Salmonella typhi CVD 908. By immunoblot and ELISA, rCSP expression was greater from a multicopy plasmid than from the single chromosomal gene. CVD 908 omega (delta aroC1019::tacP-rcsp) was well tolerated by 10 volunteers who were fed two doses of 5 x 10(7) organisms 8 days apart. Seven subjects excreted the vaccine strain for 1-3 days. All subjects developed serologic responses to O and H antigens of the live vector, whereas 3 vaccinees responded to the foreign antigen: 1 developed an 80-fold rise in serum anti-sporozoite antibody, another had a 4-fold rise in antibody to a recombinant portion of CSP (residues 309-345), while a third vaccinee developed CSP-specific CD8+ cytotoxic T lymphocyte activity. This is the first report of attenuated S. typhi eliciting a human serologic or a cytotoxic T lymphocyte response to a foreign protein. Improved foreign gene expression should enhance immunogenicity.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore 21201.
authors.forename: C
authors.initials: C
authors.lastname: Gonzalez
authors.forename: D
authors.initials: D
authors.lastname: Hone
authors.forename: F R
authors.initials: FR
authors.lastname: Noriega
authors.forename: C O
authors.initials: CO
authors.lastname: Tacket
authors.forename: J R
authors.initials: JR
authors.lastname: Davis
authors.forename: G
authors.initials: G
authors.lastname: Losonsky
authors.forename: J P
authors.initials: JP
authors.lastname: Nataro
authors.forename: S
authors.initials: S
authors.lastname: Hoffman
authors.forename: A
authors.initials: A
authors.lastname: Malik
authors.forename: E
authors.initials: E
authors.lastname: Nardin
authors.forename: M B
authors.initials: MB
authors.lastname: Sztein
authors.forename: D G
authors.initials: DG
authors.lastname: Heppner
authors.forename: T R
authors.initials: TR
authors.lastname: Fouts
authors.forename: A
authors.initials: A
authors.lastname: Isibasi
authors.forename: M M
authors.initials: MM
authors.lastname: Levine
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D016052:Protozoan Vaccines; D012485:Salmonella typhi / Q000235:genetics*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017931:DNA Primers; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan