Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

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. Synopsis Although vaccination has strongly reduced the incidence of whooping cough in many countries, this disease still causes approximately 300,000 deaths per year, mainly in young children that are not fully vaccinated. Efficient protection against pertussis requires at least three vaccine doses and is not achieved before the age of 6 mo. A new strategy to induce strong protective immunity in neonates is to mimic as closely as possible natural infection without inducing the disease, by the use of a live attenuated B. pertussis strain to be given as a single-dose nasal vaccine. The authors examined in the mouse model the efficacy of a genetically attenuated strain, BPZE1. This strain colonizes the mouse respiratory tract, but appears to be highly attenuated as evidenced by histopathological studies. In addition, a single nasal administration of this strain protects against challenge with virulent B. pertussis better than two administrations of acellular vaccine in infant mice. Moreover, BPZE1 provides protection against infection with Bordetella parapertussis responsible for a milder pertussis-like syndrome, which was not seen after vaccination with acellular vaccine. These results show that BPZE1 could be an efficient, single-dose nasal vaccine to protect early in life against whooping cough.