The Unit continued work on the development of new vaccines against Shigella flexneri and Bacillus anthracis, products are currently in clinical trials. A production and purification procedures for recombinant Pseudomonas aeruginosa exotoxin A was developed and gram quantities of the protein were made. This protein was used for the preparation of a conjugated vaccine by conjugating the protein to the bacterial polysaccharide. A production and purification procedure for obtaining inactivated protective antigen from Bacillus anthracis was established and gram quantities of this protein were made. This anthrax vaccine is being studied by using several different formulations: formaldehyde treated, formaldehyde treated with alum, alum alone, and untreated protein. Additionally, conjugating the protective antigen with the anthrax capsule is currently being prepared for clinical studies. Several proteins were prepared for evaluation as a potential candidate for conjugation, among them recombinant toxin A of Clostridium difficle and recombinant diphtheria toxoid. ? ? The Biotechnology Unit also produced large quantities of experimental recombinant malaria transmission blocking vaccine from Pichia pastoris, this work was done in collaboration with the Malaria Vaccine Development Unit of NIAID. The Unit was also involved in improving the production procedure of plasmid DNA, evaluating different host microorganisms. Significant increase in specific production was achieved by replacing the current E. coli production strain with a genetically modified strain.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2007
Total Cost
$302,558
Indirect Cost
City
State
Country
United States
Zip Code
Battistel, Marcos D; Shangold, Michael; Trinh, Loc et al. (2012) Evidence for helical structure in a tetramer of ?2-8 sialic acid: unveiling a structural antigen. J Am Chem Soc 134:10717-20
Wei, Changli; El Hindi, Shafic; Li, Jing et al. (2011) Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 17:952-60
Robbins, John B; Kubler-Kielb, Joanna; Vinogradov, Evguenii et al. (2009) Synthesis, characterization, and immunogenicity in mice of Shigella sonnei O-specific oligosaccharide-core-protein conjugates. Proc Natl Acad Sci U S A 106:7974-8
Robbins, John B; Schneerson, Rachel; Keith, Jerry M et al. (2007) The rise in pertussis cases urges replacement of chemically-inactivated with genetically-inactivated toxoid for DTP. Vaccine 25:2811-6
Kubler-Kielb, Joanna; Majadly, Fathy; Wu, Yimin et al. (2007) Long-lasting and transmission-blocking activity of antibodies to Plasmodium falciparum elicited in mice by protein conjugates of Pfs25. Proc Natl Acad Sci U S A 104:293-8
Herrmann, John E; Wang, Shixia; Zhang, Chuanyou et al. (2006) Passive immunotherapy of Bacillus anthracis pulmonary infection in mice with antisera produced by DNA immunization. Vaccine 24:5872-80
Wade, Terri K; Saksena, Rina; Shiloach, Joseph et al. (2006) Immunogenicity of synthetic saccharide fragments of Vibrio cholerae O1 (Ogawa and Inaba) bound to Exotoxin A. FEMS Immunol Med Microbiol 48:237-51