AbstractBackgroundBPZE1, a live attenuated intranasal (IN) pertussis vaccine, is designed to prevent Bordetella pertussis (Bp) infection, disease and transmission to address limitations of current pertussis vaccines. BPZE1 has been shown to protect adults, primed with whole cell pertussis vaccine in infancy, from colonization with virulent Bp. This study assessed BPZE1-induced immune responses, non-interference and safety when administered with and without tetanus-diphtheria-acellular pertussis vaccine (Tdap; Boostrix™) in children 6-17 years old, primed in infancy with acellular pertussis vaccine (aPV).Methods366 healthy school-age participants were randomized 1:1:1 to 109 CFU BPZE1+intramuscular placebo, 109 CFU BPZE1+Tdap, or Tdap+IN placebo, and then vaccinated accordingly. Primary endpoints were geometric mean fold rise (GMFR) from baseline of nasal mucosal secretory immunoglobulin A (S-IgA) against whole cell pertussis extract (WCE) at Day 29 in BPZE1 and BPZE1+Tdap groups and solicited adverse events (AEs) through 7 days after vaccination. Key secondary endpoints were BPZE1+Tdap induction of serum IgG against tetanus, diphtheria, and aPV antigens compared with Tdap at Day 29.ResultsGMFRs of S-IgA against WCE were similar among BPZE1 and BPZE1+Tdap groups (3.8 [95% CI 3.1-4.7] and 3.4 [2.8-4.2]), but low in Tdap group (1.2 [1.0-1.5]). All participants in BPZE1+Tdap and Tdap groups had anti-tetanus and anti-diphtheria antibody levels ≥0.1 IU/mL at Day 29. Serum IgG responses to PRN, FHA, and PT (aPV components) were similar between BPZE1+Tdap and Tdap groups (Table). Solicited AEs were 48%, 66%, 72% (local skin); 50%, 52%, 45% (nasal/respiratory); 42%, 50%, 55% (systemic) in BPZE1, BPZE1+Tdap and Tdap groups respectively. Three participants had SAEs unrelated to vaccination, no participants discontinued due to AE, and unsolicited AEs were similar between groups.ConclusionIntranasal BPZE1 vaccination with or without Tdap demonstrated a favorable safety profile and induced robust nasal mucosal and non-interfering systemic immunogenicity in school-age children who had been primed with aPV as infants. In contrast to Tdap, BPZE1 has the potential to both protect against Bp colonization and reduce Bp transmission.DisclosuresSaul N. Faust, FRCPCH PhD, AstraZeneca: Grant/Research Support|BioNTech: Grant/Research Support|GSK: Grant/Research Support|Iliad Biotechnologies: Grant/Research Support|J&J: Grant/Research Support|J&J: Advisor, no personal payments (all honoraria paid to employing hospital)|Moderna: Grant/Research Support|Novavax: Advisor, no personal payments (all honoraria paid to employing hospital)|Pfizer: Advisor, no personal payments (all honoraria paid to employing hospital)|Sanofi: Grant/Research Support|Sanofi: Advisor, no personal payments (all honoraria paid to employing hospital)|Valneva: Grant/Research Support Javier Céspedes, MD, ILiAD Biotechnologies: Grant/Research Support Lydiana Avila, MD, ILiAD biotechnologies: Grant/Research Support Gabriela Ivankovich-Escoto, MD, Iliad: Honoraria Helen Marshall, MD, ILiAD biotechnologies: Grant/Research Support Peter Richmond, MBBS, ILiAD biotechnologies: Grant/Research Support Terry Nolan, MD, PhD, ILiAD biotechnologies: Grant/Research Support Jolanta Bernatoniene, FRCPCH PhD, Iliad Biotechnologies: Grant/Research Support Srini Bandi, MD, Iliad Biotechnologies: Grant/Research Support Anil Shenoy, FRCPCH, Iliad Biotechnologies: Grant/Research Support Camille Locht, PhD, ILiAD biotechnologies: Advisor/Consultant|ILiAD biotechnologies: Grant/Research Support Peter Goldstein, n/a, ILiAD Biotechnologies LLC: Employee|ILiAD Biotechnologies LLC: Stocks/Bonds (Private Company) Ken Solovay, n/a, ILiAD biotechnologies: Employee|ILiAD biotechnologies: Stocks/Bonds (Private Company) Keith Rubin, MD, ILiAD Biotechnologies: Board Member|ILiAD Biotechnologies: Ownership Interest|ILiAD Biotechnologies: Stocks/Bonds (Private Company) Stephanie Noviello, MD, MPH, ILiAD Biotechnologies: Employee|ILiAD Biotechnologies: Stocks/Bonds (Private Company)
