Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague.

Abstract

A Yersinia pseudotuberculosis PB1+ (Yptb PB1+) mutant strain combined with chromosome insertion of the caf1R-caf1A-caf1M-caf1 operon and deletions of yopJ and yopK, χ10068 [pYV-ω2 (ΔyopJ315 ΔyopK108) ΔlacZ044::caf1R-caf1M-caf1A-caf1] was constructed. Results indicated that gene insertion and deletion did not affect the growth rate of χ10068 compared to wild-type Yptb cultured at 26 °C. In addition, the F1 antigen in χ10068 was synthesized and secreted on the surface of bacteria at 37 °C (mammalian body temperature), not at ambient culture temperature (26 °C). Immunization with χ10068 primed antibody responses and specific T-cell responses to F1 and YpL (Y. pestis whole cell lysate). Oral immunization with a single dose of χ10068 provided 70% protection against a subcutaneous (s.c.) challenge with ∼ 2.6 × 10(5) LD50 of Y. pestis KIM6+ (pCD1Ap) (KIM6+Ap) and 90% protection against an intranasal (i.n.) challenge with ∼ 500 LD50 of KIM6+Ap in mice. Our results suggest that χ10068 can be used as an effective precursor to make a safe vaccine to prevent plague in humans and to eliminate plague circulation among humans and animals.

• Authors: Wei Sun, Shilpa Sanapala, Hannah Rahav, Roy Curtiss 3rd
• Journal: Vaccine (Vaccine) Vol. 33 Issue 48 Pg. 6727-35 (Nov 27 2015) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 26514425 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Bacterial
• Bacterial Proteins
• Plague Vaccine
• Vaccines, Attenuated
• Virulence Factors
• caf1 protein, Yersinia pestis

Topics

• Administration, Oral
• Animals
• Antibodies, Bacterial (immunology)
• Bacterial Proteins (genetics, immunology)
• Disease Models, Animal
• Female
• Gene Deletion
• Mice
• Mutagenesis, Insertional
• Plague (immunology, prevention & control)
• Plague Vaccine (administration & dosage, immunology)
• Survival Analysis
• T-Lymphocytes (immunology)
• Vaccines, Attenuated (administration & dosage, immunology)
• Virulence
• Virulence Factors (genetics)
• Yersinia pseudotuberculosis (genetics, immunology, pathogenicity)