Adjuvant effect of TLR7 agonist adsorbed on aluminum hydroxide (AS37): A phase I randomized, dose escalation study of an AS37-adjuvanted meningococcal C conjugated vaccine.


Journal

Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537

Informations de publication

Date de publication:
12 2019
Historique:
received: 07 02 2019
revised: 02 08 2019
accepted: 17 10 2019
pubmed: 2 11 2019
medline: 21 5 2020
entrez: 1 11 2019
Statut: ppublish

Résumé

An adjuvant system (AS37) has been developed containing a synthetic toll-like receptor agonist (TLR7a). We conducted a phase I randomized, observer-blind, dose-escalation study to assess the safety and immunogenicity of an investigational AS37-adjuvanted meningococcus C (MenC) conjugate vaccine in healthy adults (NCT02639351). A control group received a licensed MenC conjugate alum-adjuvanted vaccine. Eighty participants were randomized to receive one dose of control or investigational vaccine containing AS37 (TLR7a dose 12.5, 25, 50, 100 μg). All vaccines were well tolerated, apart from in the TLR7a 100 μg dose group, which had three reports (18.8%) of severe systemic adverse events. Four weeks after vaccination, human complement serum bactericidal assay seroresponse rates against MenC were 56-81% in all groups, and ELISA seroresponses were ≥81% for all AS37-adjuvanted vaccine groups (100% in 50 and 100 μg dose groups) and 88% in the control group. Antibody responses were maintained at six months after vaccination.

Identifiants

pubmed: 31669193
pii: S1521-6616(19)30073-7
doi: 10.1016/j.clim.2019.108275
pii:
doi:

Substances chimiques

Adjuvants, Immunologic 0
Antibodies, Bacterial 0
Bacterial Vaccines 0
Meningococcal Vaccines 0
TLR7 protein, human 0
Toll-Like Receptor 7 0
serogroup C meningococcal conjugate vaccine 0
Aluminum Hydroxide 5QB0T2IUN0

Banques de données

ClinicalTrials.gov
['NCT02639351']

Types de publication

Clinical Trial, Phase I Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108275

Informations de copyright

Copyright © 2019 GlaxoSmithKline Biologicals S.A. Published by Elsevier Inc. All rights reserved.

Auteurs

Antonio Gonzalez-Lopez (A)

GSK Slaoui Center for Vaccines Research, 14200 Shady Grove Rd, Rockville, MD, USA.

Jaap Oostendorp (J)

GSK Slaoui Center for Vaccines Research, 14200 Shady Grove Rd, Rockville, MD, USA.

Thomas Koernicke (T)

PAREXEL International GmbH, Spandauer Damm 130, D-14050 Berlin, Germany.

Tommaso Fadini (T)

PAREXEL International GmbH, Spandauer Damm 130, D-14050 Berlin, Germany.

Ugo D'Oro (U)

GSK, Via Fiorentina 1, Siena, Italy.

Sherryl Baker (S)

GSK Slaoui Center for Vaccines Research, 14200 Shady Grove Rd, Rockville, MD, USA.

Derek T O'Hagan (DT)

GSK Slaoui Center for Vaccines Research, 14200 Shady Grove Rd, Rockville, MD, USA.

Giuseppe Del Giudice (G)

GSK, Via Fiorentina 1, Siena, Italy.

Emilio Siena (E)

GSK, Via Fiorentina 1, Siena, Italy.

Oretta Finco (O)

GSK, Via Fiorentina 1, Siena, Italy.

Duccio Medini (D)

GSK, Via Fiorentina 1, Siena, Italy. Electronic address: duccio.x.medini@gsk.com.

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Classifications MeSH