Immunogenicity and protective efficacy of Vibrio cholerae outer membrane vesicles in rabbit model

• Published in: FEMS immunology and medical microbiology 2010-10, Vol.60 (1), p.18-27
• Main Authors: Roy, Nivedita, Barman, Soumik, Ghosh, Amit, Pal, Amit, Chakraborty, Krishnendu, Das, Santa Sabuj, Saha, Dhira Rani, Yamasaki, Shinji, Koley, Hemanta
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antibodies; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antisera; Applied microbiology; Bacteria; Bacterial Outer Membrane Proteins - administration & dosage; Bacterial Outer Membrane Proteins - immunology; Bacterial Outer Membrane Proteins - isolation & purification; Bacteriology; Biological and medical sciences; Cholera; Cholera - pathology; Cholera - prevention & control; Cholera Vaccines - administration & dosage; Cholera Vaccines - immunology; colonization; Diarrhea; Diarrhea - pathology; Diarrhea - prevention & control; Disease Models, Animal; Fatalities; Female; Fundamental and applied biological sciences. Psychology; Homology; Immunity; Immunization; Immunogenicity; Intestine; Male; Membrane vesicles; Membranes; Microbiology; Miscellaneous; oral immunization; outer membrane vesicles (OMVs); Pathogens; rabbit model; Rabbits; RITARD model; Secretory Vesicles - immunology; Serum Bactericidal Antibody Assay; Signs and symptoms; Strains (organisms); Survival Analysis; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vesicles; Vibrio cholerae; Vibrio cholerae - immunology; Waterborne diseases
• ISSN: 0928-8244; 1574-695X; 2049-632X
• DOI: 10.1111/j.1574-695X.2010.00692.x

Abstract We show here that oral immunization with purified outer membrane vesicles (OMVs) of Vibrio cholerae induces a prolonged high rise in the protective antibody titre. Rabbit immune sera were vibriocidal against the homologous and against several heterologous V. cholerae strains in vitro. In addition, OMV immunization conferred significant protective immunity against subsequent bacterial challenges. Thirty OMV-immunized rabbits were challenged with different V. cholerae strains; each challenged group contained five immunized and three unimmunized animals. All the immunized rabbits survived bacterial challenges and were healthy after 24 h, except the two from each group that received the SG24 and SG06 strains, respectively, which developed watery diarrhoea. In contrast, all the unimmunized animals developed cholera-like symptoms, with a death toll of eight within 24 h of challenge. This is the first report of the induction of protective immunity by V. cholerae OMVs in a rabbit model (removable intestinal tie-adult rabbit diarrhoea) that mimics the human disease. Finally, OMVs were found to be significantly less reactogenic than the live and the heat-killed bacteria. Our studies show that oral immunization with OMVs of V. cholerae may induce long-term immunity and may be useful as a ‘nonliving’ vaccine candidate for the future.