Salmonella typhi Vaccine Strain CVD 908 Expressing the Circumsporozoite Protein of Plasmodium falciparum: Strain Construction and Safety and Immunogenicity in Humans

• Published in: The Journal of infectious diseases Vol. 169; no. 4; pp. 927 - 931
• Main Authors: Gonzalez, Cesar, Hone, David, Noriega, Fernando R., Tacket, Carol O., Davis, Jonathan R., Losonsky, Genevieve, Nataro, James P., Hoffman, Stephen, Malik, Anita, Nardin, Elizabeth, Sztein, Marcelo B., Heppner, D. Gray, Fouts, Timothy R., Isibasi, Armando, Levine, Myron M.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.04.1994; University of Chicago Press
• Subjects: Administration, Oral; Adult; Amino Acid Sequence; Animals; Antibodies; Antibodies, Protozoan - biosynthesis; Antigens; B lymphocytes; Base Sequence; Biological and medical sciences; Cloning, Molecular; Concise Communications; DNA Primers - chemistry; Female; Gene Expression Regulation; Genes; Genetic loci; Genetic Vectors; Human protozoal diseases; Humans; Immune response; Infectious diseases; Malaria; Malaria Vaccines - administration & dosage; Malaria Vaccines - adverse effects; Malaria Vaccines - immunology; Medical sciences; Mice; Molecular Sequence Data; Parasitic diseases; Plasmodium falciparum; Plasmodium falciparum - immunology; Protozoal diseases; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Protozoan Vaccines; Salmonella typhi; Salmonella typhi - genetics; Sporozoites; T lymphocytes; Transcriptional regulatory elements; Vaccination; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology; Human; Protozoa; Protozoal disease; Malaria; Toxicity; Vaccination; Salmonella typhi; Sporozoit; Vaccine; Gene expression; Infection; Prevention; Immunoprophylaxis; Plasmodium falciparum; Immunogenicity; Production; Bacteria; Coat protein; Recombinant protein; Attenuated strain; Sporozoa; Enterobacteriaceae; Clone
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/169.4.927

resp, encoding amino acids 21-398 of Plasmodium falciparum circumsporozoite protein (CSP), under control of tacP was integrated into the chromosomal ΔaroC locus of attenuated ΔaroC, ΔaroD Salmonella typhi CVD 908. By immunoblot and ELISA, rCSP expression was greater from a multicopy plasmid than from the single chromosomal gene. CVD 908 Ω(ΔaroCI019:: tacP-resp) was well tolerated by 10 volunteers who were fed two doses of 5 × 107 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: I 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,