학술논문
Immunogenicity and safety of BPZE1, an intranasal live attenuated pertussis vaccine, versus tetanus-diphtheria-acellular pertussis vaccine: a randomised, double-blind, phase 2b trial.
Document Type
Academic Journal
Author
Keech C; ILiAD Biotechnologies, Weston, FL, USA.; Miller VE; DM Clinical Research, Texas Center for Drug Development, Houston, TX, USA.; Rizzardi B; Velocity Clinical Research, West Jordan, UT, USA.; Hoyle C; Elite Research Network, Mount Pleasant, SC, USA.; Pryor MJ; 360biolabs, Melbourne, VIC, Australia.; Ferrand J; 360biolabs, Melbourne, VIC, Australia.; Solovay K; ILiAD Biotechnologies, Weston, FL, USA.; Thalen M; ILiAD Biotechnologies, Weston, FL, USA; BioLyo Technologies, Ghent, Belgium.; Noviello S; ILiAD Biotechnologies, Weston, FL, USA. Electronic address: snoviello@iliadbiotech.com.; Goldstein P; ILiAD Biotechnologies, Weston, FL, USA.; Gorringe A; United Kingdom Health Security Agency, Porton Down, Salisbury, UK.; Cavell B; United Kingdom Health Security Agency, Porton Down, Salisbury, UK.; He Q; Institute of Biomedicine, University of Turku, Turku, Finland.; Barkoff AM; Institute of Biomedicine, University of Turku, Turku, Finland.; Rubin K; ILiAD Biotechnologies, Weston, FL, USA.; Locht C; University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Centre for Infection and Immunity of Lille, Lille, France.
Source
Publisher: Elsevier Country of Publication: England NLM ID: 2985213R Publication Model: Print Cited Medium: Internet ISSN: 1474-547X (Electronic) Linking ISSN: 01406736 NLM ISO Abbreviation: Lancet Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Bordetella pertussis epidemics persist as transmission remains unabated despite high acellular pertussis vaccination rates. BPZE1, a live attenuated intranasal pertussis vaccine, was designed to prevent B pertussis infection and disease. We aimed to assess the immunogenicity and safety of BPZE1 compared with the tetanus-diphtheria-acellular pertussis vaccine (Tdap).
Methods: In this double-blind, phase 2b trial at three research centres in the USA, healthy adults aged 18-50 years were randomly assigned (2:2:1:1) via a permuted block randomisation schedule to receive BPZE1 vaccination followed by BPZE1 attenuated challenge, BPZE1 vaccination followed by placebo challenge, Tdap followed by BPZE1 attenuated challenge, or Tdap followed by placebo challenge. On day 1, lyophilised BPZE1 was reconstituted with sterile water and given intranasally (0·4 mL delivered to each nostril), whereas Tdap was given intramuscularly. To maintain masking, participants in the BPZE1 groups received an intramuscular saline injection, and those in the Tdap groups received intranasal lyophilised placebo buffer. The attenuated challenge took place on day 85. The primary immunogenicity endpoint was the proportion of participants achieving nasal secretory IgA seroconversion against at least one B pertussis antigen on day 29 or day 113. Reactogenicity was assessed up to 7 days after vaccination and challenge, and adverse events were recorded for 28 days after vaccination and challenge. Serious adverse events were monitored throughout the study. This trial is registered with ClinicalTrials.gov, NCT03942406.
Findings: Between June 17 and Oct 3, 2019, 458 participants were screened and 280 were randomly assigned to the main cohort: 92 to the BPZE1-BPZE1 group, 92 to the BPZE1-placebo group, 46 to the Tdap-BPZE1 group, and 50 to the Tdap-placebo group. Seroconversion of at least one B pertussis-specific nasal secretory IgA was recorded in 79 (94% [95% CI 87-98]) of 84 participants in the BPZE1-BPZE1 group, 89 (95% [88-98]) of 94 in the BPZE1-placebo group, 38 (90% [77-97]) of 42 in the Tdap-BPZE1 group, and 42 (93% [82-99]) of 45 in the Tdap-placebo group. BPZE1 induced broad and consistent B pertussis-specific mucosal secretory IgA responses, whereas Tdap did not induce consistent mucosal secretory IgA responses. Both vaccines were well tolerated, with mild reactogenicity and no serious adverse events related to study vaccination.
Interpretation: BPZE1 induced nasal mucosal immunity and produced functional serum responses. BPZE1 has the potential to avert B pertussis infections, which ultimately could lead to reduced transmission and diminished epidemic cycles. These results should be confirmed in large phase 3 trials.
Funding: ILiAD Biotechnologies.
Competing Interests: Declaration of interests CK, KS, MT, PG, KR, and SN are equity holders in, and current or former employees of or consultants to, ILiAD Biotechnologies. VEM reports leadership of the Pearl institutional review. SN is a former employee of Novartis. AG has received honoraria from Sanofi Pasteur. CL holds patents on the BPZE1 vaccine (licensed to ILiAD Biotechnologies) and reports consulting fees from, and holds equity in, ILiAD Biotechnologies. All other authors declare no competing interests.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Methods: In this double-blind, phase 2b trial at three research centres in the USA, healthy adults aged 18-50 years were randomly assigned (2:2:1:1) via a permuted block randomisation schedule to receive BPZE1 vaccination followed by BPZE1 attenuated challenge, BPZE1 vaccination followed by placebo challenge, Tdap followed by BPZE1 attenuated challenge, or Tdap followed by placebo challenge. On day 1, lyophilised BPZE1 was reconstituted with sterile water and given intranasally (0·4 mL delivered to each nostril), whereas Tdap was given intramuscularly. To maintain masking, participants in the BPZE1 groups received an intramuscular saline injection, and those in the Tdap groups received intranasal lyophilised placebo buffer. The attenuated challenge took place on day 85. The primary immunogenicity endpoint was the proportion of participants achieving nasal secretory IgA seroconversion against at least one B pertussis antigen on day 29 or day 113. Reactogenicity was assessed up to 7 days after vaccination and challenge, and adverse events were recorded for 28 days after vaccination and challenge. Serious adverse events were monitored throughout the study. This trial is registered with ClinicalTrials.gov, NCT03942406.
Findings: Between June 17 and Oct 3, 2019, 458 participants were screened and 280 were randomly assigned to the main cohort: 92 to the BPZE1-BPZE1 group, 92 to the BPZE1-placebo group, 46 to the Tdap-BPZE1 group, and 50 to the Tdap-placebo group. Seroconversion of at least one B pertussis-specific nasal secretory IgA was recorded in 79 (94% [95% CI 87-98]) of 84 participants in the BPZE1-BPZE1 group, 89 (95% [88-98]) of 94 in the BPZE1-placebo group, 38 (90% [77-97]) of 42 in the Tdap-BPZE1 group, and 42 (93% [82-99]) of 45 in the Tdap-placebo group. BPZE1 induced broad and consistent B pertussis-specific mucosal secretory IgA responses, whereas Tdap did not induce consistent mucosal secretory IgA responses. Both vaccines were well tolerated, with mild reactogenicity and no serious adverse events related to study vaccination.
Interpretation: BPZE1 induced nasal mucosal immunity and produced functional serum responses. BPZE1 has the potential to avert B pertussis infections, which ultimately could lead to reduced transmission and diminished epidemic cycles. These results should be confirmed in large phase 3 trials.
Funding: ILiAD Biotechnologies.
Competing Interests: Declaration of interests CK, KS, MT, PG, KR, and SN are equity holders in, and current or former employees of or consultants to, ILiAD Biotechnologies. VEM reports leadership of the Pearl institutional review. SN is a former employee of Novartis. AG has received honoraria from Sanofi Pasteur. CL holds patents on the BPZE1 vaccine (licensed to ILiAD Biotechnologies) and reports consulting fees from, and holds equity in, ILiAD Biotechnologies. All other authors declare no competing interests.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)