Study Title: A Phase 2b, Multi-Center, Placebo-Controlled, Randomized Study of BPZE1 Intranasal Pertussis Vaccine in Healthy School-Age Children to Assess the Immunological Response and Safety Profile of a Single Dose BPZE1 With and Without Co-Administration of Tetanus, Diphtheria, and Acellular Pertussis (Boostrix™)
Chief Medical Officer and Executive VP of Clinical Research: Cheryl Keech, MD, PhD ILiAD Biotechnologies
Sponsor: ILiAD Biotechnologies
Acellular pertussis (aP) vaccines were introduced into most developed countries in the late 1990’s and early 2000’s, and for 2 decades, children in these countries have received only aP vaccinations. The resurgence of Bordetella pertussis (B. pertussis) in these countries, despite high vaccination rates, is hypothesized to be linked to the sole use of aP vaccines, which do not alter B. pertussis acquisition and have limited durability. The availability of a cost-effective pertussis vaccine that provides improved efficacy and prolonged protection with the potential to reduce or eliminate transmission would present a breakthrough in the prevention of colonizing B. pertussis infections. The current pertussis vaccine strategies do not provide mucosal immunity or alter B. pertussis acquisition and therefore have not been successful in halting human-to-human transmission. As humans are the only known reservoir for B. pertussis, targeting colonization would provide a novel approach through mucosal-induced immunity to reduce the B. pertussis reservoir in the population and thereby reduce transmission. The timing of aP vaccine introduction has resulted in a school-age population who could benefit from a broader immune response achievable with a live attenuated pertussis vaccine such as BPZE1.
The intranasally administered BPZE1 live attenuated vaccine provides an opportunity to generate a locally effective mucosal antibody response at the site of potential exposure, mimic the route of entry of the wild-type pathogen, and induce a broader immune response as measured by cellular, mucosal, and serum indices. Inducing mucosal immunity with an attenuated live vaccine delivered through intranasal vaccination could halt progression from upper airway to lower airway disease in BPZE1-vaccinated individuals as well as strengthen herd immunity by reducing upper airway person-to-person transmission. The overall effect would be improved protection of even the most vulnerable from B. pertussis through a robust booster vaccination strategy with the best potential to disrupt B. pertussis epidemics.
Acellular pertussis vaccines are currently recommended worldwide as booster vaccinations. The current recommendation in the United Kingdom includes the childhood booster of DTaP at 3 years of age with no adolescent booster, whereas other European/Commonwealth countries have a similar DTaP vaccination schedule but have added a tetanus toxoid, reduced diphtheria toxoid, and reduced antigen content acellular pertussis (Tdap) booster during the school age period (up to and including adolescence). This study will investigate BPZE1-induced immune responses in a background of DTaP or Tdap, with the last DTaP or Tdap booster occurring more than 3 years prior. BPZE1 alone as well as coadministration with Boostrix will be investigated to test safety and whether augmenting/broadening immune responses are possible compared to Boostrix alone in an aP primed-only population. Furthermore, the testing of interference of BPZE1 with all components found in Boostrix will be investigated. Lastly, demonstrating protection against subsequent colonization using the attenuated challenge model (re-vaccination/attenuated challenge with BPZE1) will be investigated at 3 months following initial vaccination (optional substudy). As this population has never received a whole cell pertussis (wP) vaccination, this will be the first time that a broader immunization against B. pertussis is provided; therefore, additional hypotheses include that a single intranasal vaccination with BPZE1 will be sufficient to induce a differential immune response compared to Boostrix (e.g. mucosal immunity induction and reduction in B. pertussis acquisition), and a differential cellular mediated response will be investigated following vaccination with either BPZE1, BPZE1+Boostrix or Boostrix.