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

Abstract

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.

Attenuated Bordetella pertussis Vaccine Candidate BPZE1 Promotes Human Dendritic Cell CCL21-Induced Migration and Drives a Th1/Th17 Response

“…Protection against B. pertussis was comparable with that induced by two injections of acellular vaccine in adult mice and was significantly better than that induced by two administrations of acellular vaccine in infant mice (3). Moreover, histopathological and physiological studies in mice confirmed that B. pertussis BPZE1 is highly attenuated, although it is still able to transiently colonize the mouse respiratory tract and thereby induce strong protection upon a single intranasal administration (4).…”

“…Studies in mice have shown that the live attenuated B. pertussis strain BPZE1 is a promising candidate as a new effective pertussis vaccine for young children (3)(4)(5)16). Preclinical proof of concept has been established in murine models.…”

“…B. pertussis BPSMDN was constructed by deleting the DNT gene in B. pertussis BPSM using the pJQmp200rpsL18 derivative described in Ref. 3.…”

“…Recently, a novel live attenuated B. pertussis vaccine strain, BPZE1, has been developed by eliminating or detoxifying three important B. pertussis virulence factors (3). Pertussis toxin (PT) was genetically detoxified, resulting in inactivation of the toxin without altering its immunogenicity.…”

Development of improved vaccines against whooping cough: Current status

“…pertussis in which PT gene was deleted was reported to be attenuated by its inability to cause severe infection in mice without affecting the ability of the bacteria to colonize the respiratory tract and protect mice against challenge with the wild type. 140 More recently, a live attenuated B. pertussis mutant strain (BPZE1) in which PT was genetically detoxified PT, dermonecrotoxin [DNT] gene deleted and B. pertussis ampG replaced by E. coli ampG to minimize its activity, was reported to induce protection in young mice after a single nasal administration 141 and reported to be safe in adult interferon-γ receptor deficient adult mice. 142 However, this strain survived in lungs as long as the wild type strain.…”