Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough

• Published in: PLoS pathogens Vol. 2; no. 7; p. e65
• Main Authors: Mielcarek, Nathalie, Debrie, Anne-Sophie, Raze, Dominique, Bertout, Julie, Rouanet, Carine, Younes, Amena Ben, Creusy, Colette, Engle, Jacquelyn, Goldman, William E, Locht, Camille
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2006; Public Library of Science (PLoS)
• Subjects: Administration, Intranasal; Age; Age Factors; Animals; Animals, Newborn - immunology; Antibodies, Bacterial - immunology; Antigens, Bacterial - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - therapeutic use; Biotechnology; Bordetella parapertussis; Bordetella pertussis; Bordetella pertussis - genetics; Bordetella pertussis - immunology; Bordetella pertussis - pathogenicity; Cytokines; Dose-Response Relationship, Drug; Drug therapy; Eubacteria; Experiments; Female; Immunization - methods; Immunology; Infections; Infectious Diseases; Lungs; Mice; Mice, Inbred BALB C; Microbiology; Mortality; Pediatrics; Physiological aspects; Respiratory System - microbiology; Respiratory System - pathology; Tuberculosis; Vaccines; Vaccines, Acellular - administration & dosage; Vaccines, Acellular - therapeutic use; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - therapeutic use; Whooping cough; Whooping Cough - immunology; Whooping Cough - physiopathology; Whooping Cough - prevention & control; France; United States > US
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.0020065

Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth.