Vaccine Development Program

Our Vaccine development program includes the following areas

Human Health

Vaccine against: Organism(s): Description:
Infant pneumonia and otitis media Streptococcus pneumoniae Our objective is to design, construct and evaluate a RASV delivering multiple protective pneumococcal protein antigens to be deliverd orally to newborns and infants to confer protective immunity to all pneumococcal serotypes. The vaccine prototype has been demonstrated to be totally safe in newborn, pregnant, malnourished and immunodeficient mice and the collective preclinical data led to FDA approval and the granting of an IND license. Human clinical dose escalation trials with doses up to 1010 CFU have been completed with no adverse reactions, essentially no bacteremias and no shedding of viable vaccine cells in stools. Although totally safe, the RASV constructs were not as immunogenic as desired but strains with the RpoS+ phenotype gave better results than the vaccine strain that was RpoS. A selected strain has been further improved to significantly enhance immunogenicity without compromising safety attributes. This isolate will be evaluated in human trials. The vaccine is also designed to confer protective immunity to diverse Salmonella serotypes causing diarrheal disease.

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Dysentery Shigella species Shigella dysentary is an extreme diarrheal disease with bloody stools and some 50 to 100 thousand deaths per year. Our objective is to design, construct and evaluate a RASV platform antigen delivery system to induce protective immunity to diverse Salmonella serotypes and other enteric bacteria in the Enterobacteriaceae and will also deliver several conserved protective Shigella antigens to augment induction of protective immunity to diverse Shigella species and serotypes.
Diarrheal diseases E. coli (ETEC) ETEC is a common cause of “traveler’s” diarrhea and a leading cause of bacterially induced diarrhea in children in the developing world. Our objective is to design, construct and evaluate a RASV platform antigen delivery system to induce protective immunity to diverse Salmonella serotypes and other enteric bacteria in the Enterobacteriaceae and will also deliver several conserved protective ETEC antigens to augment induction of protective immunity to prevent ETEC-induced diarrheal disease.
Diarrheal diseases Yersinia pseudotuberculosis and
Yersinia enterocolitica
We are using our RASV platform antigen delivery system to induce protective immunity to diverse Salmonella serotypes and other enteric bacteria in the Enterobacteriaceae (which includes Yersinia species) and will also deliver several conserved protective Yersinia antigens to augment induction of protective immunity to both Y. pseudotuberculosis and Y. entercolitica that are responsible for some diarrheal disease. We are also developing a recombinant attenuated Y. psuedotuberculosis vaccine to immunize zoonotic rodent reservoirs carrying Y. pestis to hopefully decrease these reservoirs.

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Bubonic plague, Pneumonic plague Yersinia pestis Plague is endemic in rodent populations in many areas of the world, including the western United States.  It is also a potential bioweapon. We are using our RASV platform antigen delivery system to induce protective immunity to diverse Salmonella serotypes and other enteric bacteria in the Enterobacteriaceae (which includes Yersinia species) and will also deliver several conserved protective Y. pestis antigens to augment induction of protective immunity to Y. pestis. We have had considerable success and will soon propose to evaluate these RASVs in human volunteers. May also use these vector systems as part of a program to vaccinate wild rodents to reduce zoonotic reservoirs. We are also constructing an attenuated Y. pestis vaccine strain.

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Tuberculosis Mycobacterium tuberculosis A scourge to humankind throughout recorded history, tuberculosis (TB) continues to have a devastating impact even today. The World Health Organization has estimated that one-third of the world’s population is infected with M. tuberculosis, with approximately 8 million new cases diagnosed annually. Although not everyone who is infected develops active disease, of those who do, nearly two million die each year. We are employing the recombinant attenuated Salmonella vaccine systems with regulated delayed lysis in vivo to synthesize M. tuberculosis antigens and to deliver them to optimal sites within immunized individuals to generate protective mucosal, systemic and cellular immune responses against the tubercle bacilli.

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Enteric and typhoid fevers Salmonella Typhi and
Paratyphi A
We are using S. Paratyphi A and S. Typhi as attenuated vectors for RASVs to deliver multiple protective antigens from pneumococcal strains, Shigella, Yersinia species, M. tuberculosis and influenza virus to prevent infections by these pathogens.  Enteric fever is similar to but is a much milder disease than typhoid fever. Since the incidence of enteric fever is increasing globally, we may use some of our attenuated strains as vaccines against enteric fever and possibly against typhoid fever.
Gastric ulceration and gastritis
Helicobacter pylori
Although H. pylori is a commensal in human. It could cause ulcers in the stomach and small intestine.
Cancer N/A S. Typhimurium strains have been extensively modified as therapeutic vaccines to destroy solid tumors or induce clearance of other cancers. Many of these strains exhibit the regulated delayed lysis in vivo phenotype and deliver antigens to cause tumor cell death or augment immune responses to induce cncer cell elimination.

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Influenza virus We are using extensively modified RASVs with the regulated delayed lysis in vivo phenotype to deliver (i) concerved M2e sequences fused to the woodchuck hepatitis virus core, (ii) the conserved NP antigen with fusion to additional conserved T-cell epitopes to the cytosol for class I presentation and (iii) Dna vaccines delivered to the cell nucleus for synthesis of variable HA antigens. In all cases, high-level protective immunity has been induced to challenge with influenza virus in mice.

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Animal Health

Vaccine against: Organism(s): Description:
Avian Pathogenic E. coli E. coli (APEC) We have developed a RASV platform antigen delivery system to induce protective immunity to diverse Salmonella serotypes and other enteric bacteria in the Enterobacteriaceae. This S. Typhimurium strain is being further modified to deliver APEC-specific antigens to induce protective immunity to APEC strains that cause significant mortality and carcas condemnation at slaughter. The use of this Food Safety vaccine will thus have a positive economic benefit to poultry producers.

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Necrotic enteritis Clostridium perfringens Necrotic enteritis results in significant economic losses to the poultry industry, particularly in light of recent efforts to eliminate the use of growth promoting antibiotics when rearing birds.  We are of the opinion that C. perfringens is also responsible for low-grade diarrheas in the developing world and that it is under-reported, so it is also included as part of our enteric diseases program for humans. We have constructed Food Safety RASVs derived from attenuated S. Typhimurium strains designed to induce cross-protective immunity against diverse Salmonella serotypes and protect against C. perfringens colonization and persistance by delivering C. perfringens conserved protective antigens. These Food Safety vaccines can be administered by course spray to newly hatched chicks in the hatchery with a later boost immunization administered in drinking water to chicks on the broiler production facility.

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Fish Pathogens Edwardsiella ictaluri and E.tarda The largest aquaculture industry in the United States is the production of channel catfish (Ictalurus punctatus), trout and salmon. The most serious bacterial pathogen affecting this industry is Edwardsiella ictaluri, causing an estimated $50-80 million in annual losses. Our objective is to develop a non-virulent and antibiotic-sensitive E. ictaluri and/or E.tarda strain that will prevent E. ictaluri and/or E.tarda infections in channel catfish, trout and salmon using a bath/oral vaccine along with an economical boost immunization through food. An E. ictaluri and/or E.tarda vaccine vector can have additional applications for virus/parasite antigen delivery or DNA vaccine delivery for protection against other important pathogens of the aquaculture industry. For additional scientific details and references visit fishvac.com.

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Coccidiosis Eimeria Coccidiosis is a devestating disese in poultry with several Eimeria species important for most of the morbidity and mortality in the poultry industry. We are using several RASV platforms toward developing a vaccine to prevent this disease and eliminate the need to rely on expensice coccidiostats that also result in parsite resistance.

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 C. jejuni  Campylobacter jejuni Campylobacter jejuni is a comensal in poultry but is often transmitted through the food chain to cause dirrheal disease in humans at a level equal to or greater than the food transmitted Salmonella causing diarrheal disease in humans. An RASV delivering antigens conferring protective immunity to C. jejuni would thus represent an important Food Safety vaccine for poultry.

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Salmonellosis Salmonella enterica Choleraesuis and Dublin  S. Choleraesuis and Dublin are associated with enteritis, typhoid, respiratory disease in swine and cattle, respectively. They can also infect humans through the food chain. An RASV could induce cross-protective immunity to both serotypes would be an important Food Safety vaccine.

Vaccines