Phase 1 trial of an investigational Tdap booster vaccine with CpG 1018 adjuvant compared with Boostrix in healthy adults and adolescents.

Autor: Richmond P; University of Western Australia School of Medicine, Department of Immunology, Perth Children's Hospital and Telethon Kids Institute, Nedlands, WA, Australia., Nolan T; Vaccine and Immunisation Research Group (VIRGo), Peter Doherty Institute for Infection and Immunity at the University of Melbourne and Murdoch Children's Research Institute, Melbourne, VIC, Australia., McGirr A; Northern Beaches Clinical Research, Brookvale, NSW, Australia., Napier-Flood F; Paratus Clinical Research Western Sydney, Blacktown, NSW, Australia., Kim J; Paratus Clinical Research Central Coast, Kanwal, NSW, Australia., Leah A; Paratus Clinical Research Canberra, Bruce, ACT, Australia., Xie F; Dynavax Technologies Corporation, Emeryville, CA, USA., Campbell JD; Dynavax Technologies Corporation, Emeryville, CA, USA., Godeaux O; ZAM Consulting, Brussels, Belgium., Henry O; Dynavax Technologies Corporation, Emeryville, CA, USA., Wood N; Kids Research, The Children's Hospital at Westmead, Westmead, NSW, Australia., Janssen RS; Dynavax Technologies Corporation, Emeryville, CA, USA. Electronic address: rjanssen@dynavax.com.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2024 Oct 24; Vol. 42 (24), pp. 126251. Date of Electronic Publication: 2024 Sep 02.
DOI: 10.1016/j.vaccine.2024.126251
Abstrakt: This phase 1 trial assessed the safety and immunogenicity of an investigational tetanus/diphtheria/acellular pertussis vaccine combined with CpG 1018 adjuvant 1500 μg (Tdap-1018 1500 μg) or 3000 μg (Tdap-1018 3000 μg) in adults and adolescents. In this randomized, active-controlled, multicenter, dose-escalation trial, healthy participants aged 10 to 22 years received 1 dose of Tdap-1018 1500 μg, Tdap-1018 3000 μg, or Boostrix. Geometric mean concentrations (GMCs) and booster response rates (BRRs) for antibodies against pertussis (pertussis toxin, filamentous hemagglutinin, pertactin), tetanus, and diphtheria antigens, and neutralizing antibodies against pertussis toxin were assessed 4 weeks after vaccination. Safety and tolerability were assessed for solicited post-injection reactions within 7 days after vaccination and unsolicited adverse events up to 12 weeks after vaccination. Of 117 enrolled participants, 80 adults (92%) and 30 adolescents (100%) completed the study. Both Tdap-1018 formulations were generally well tolerated, with no vaccine-related serious adverse events. Frequency and severity in post-injection reactions after Tdap-1018 administration were similar to Boostrix except for higher proportions of moderate pain for Tdap-1018. In adults at week 4, ratio of GMCs and BRRs for all antigens in the 3000-μg group were similar to or higher than Boostrix, with significantly higher GMC ratios for anti-pertussis toxin (2.1 [1.5-3.0]) and anti-tetanus (1.8 [1.1-2.9]) and significantly higher BRRs for anti-pertussis toxin (difference [95% CI]: 34.5% [13.4-54.6]), anti-pertactin (19.2% [4.4-38.1]), and anti-tetanus (30.0% [3.6-52.7]) antibodies. For adolescents, in the 3000-μg group, ratio of GMCs and BRRs were similar to or higher than Boostrix for all antigens. Both Tdap-1018 formulations showed acceptable safety and tolerability profiles. Tdap-1018 3000 μg induced similar or higher immune responses than Boostrix. ACTRN12620001177943 (Australian New Zealand Clinical Trials Registry; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12620001177943p).
Competing Interests: Declaration of competing interest F.X. and O.G. are consultants for Dynavax Technologies Corporation. J.D.C., O.H., and R.S.J. are employees of Dynavax Technologies Corporation and may hold company stock. P.R. has served on pertussis vaccine scientific advisory boards on behalf of his institution for GlaxoSmithKline and Sanofi outside the submitted work. T.N. has served on vaccine scientific advisory boards for GSK, Sanofi, Pfizer, CSL Seqirus, MSD, Moderna, and AstraZeneca, and on clinical trial data and safety monitoring boards for GSK, CSL Seqirus, Statens Serum Institute, SK Bioscience Korea, Zeria Pharmaceuticals, Clover, Novavax, Serum Institute of India, and Moderna. A.M., F.N-F., J.K., A.L., and N.W. report no potential conflicts.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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