SALMONELLA-TYPHI VACCINE STRAIN CVD-908 EXPRESSING THE CIRCUMSPOROZOITE PROTEIN OF PLASMODIUM-FALCIPARUM - STRAIN CONSTRUCTION AND SAFETY AND IMMUNOGENICITY IN HUMANS

rcsp, encoding amino acids 21-398 of Plasmodium falciparum circumsporo zoite protein (CSP), under control of P-tac was integrated into the ch romosomal Delta aroC locus of attenuated Delta aroC, Delta aroD Salmon ella typhi CVD 908. By immunoblot and ELISA, rCSP expression was great er from a multicopy plasmid than from the single chromosomal gene. CVD 908 Omega(Delta aroC1019::P-tac-rcsp) was well tolerated by 10 volunt eers 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 devel oped serologic responses to O and H antigens of the live vector, where as 3 vaccinees responded to the foreign antigen: 1 developed an 80-fol d 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 ac tivity. This is the first report of attenuated S. typhi eliciting a hu man serologic or a cytotoxic T lymphocyte response to a foreign protei n. Improved foreign gene expression should enhance immunogenicity.