Local and Systemic Immunity against Respiratory Syncytial Virus Induced by a Novel Intranasal Vaccine. A Randomized, Double-Blind, Placebo-controlled Clinical Trial


Ascough, Stephanie, Vlachantoni, Iris, Kalyan, Mohini, Haijema, Bert-Jan, Wallin-Weber, Sanna, Dijkstra-Tiekstra, Margriet, Ahmed, Muhammad S ORCID: 0000-0001-6163-8102, van Roosmalen, Maarten, Grimaldi, Roberto, Zhang, Qibo et al (show 3 more authors) (2019) Local and Systemic Immunity against Respiratory Syncytial Virus Induced by a Novel Intranasal Vaccine. A Randomized, Double-Blind, Placebo-controlled Clinical Trial. American Journal of Respiratory and Critical Care Medicine, 200 (4). pp. 481-492.

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Abstract

RATIONALE:Needle-free intranasal vaccines offer major potential advantages, especially against pathogens entering via mucosal surfaces. As yet, there is no effective vaccine against respiratory syncytial virus (RSV), a ubiquitous pathogen of global importance that preferentially infects respiratory epithelial cells; new strategies are urgently required. OBJECTIVES:Here, we report the safety and immunogenicity of a novel mucosal RSV F protein vaccine linked to an immunostimulatory bacterium-like particle (BLP). METHODS:In this phase I, randomised, double-blind placebo-controlled trial, 48 healthy volunteers aged 18-49 years were randomly assigned to receive placebo or SynGEM (low- or high-dose) intranasally by prime-boost administration. The primary outcome was safety and tolerability, with secondary objectives assessing virus-specific immunogenicity. MEASUREMENTS AND MAIN RESULTS:There were no significant differences in adverse events between placebo and vaccinated groups. SynGEM induced systemic plasmablast responses and significant, durable increases in RSV-specific serum antibody in healthy seropositive adults. Volunteers given low-dose SynGEM (140 µg F, 2mg BLP) required a boost at day 28 to achieve plateau responses with a maximum fold-change of 2.4, whereas high-dose recipients (350 µg F, 5mg BLP) achieved plateau responses with a fold-change of 1.5 after first vaccination that remained elevated up to 180 days post-vaccination irrespective of further boosting. Palivizumab-like antibodies were consistently induced, but F protein site Ø-specific antibodies were not detected and virus-specific nasal IgA responses were heterogeneous, with strongest responses in individuals with lower pre-existing antibody levels. CONCLUSIONS:SynGEM is thus the first non-replicating intranasal RSV subunit vaccine to induce persistent antibody responses in human volunteers. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02958540.

Item Type: Article
Uncontrolled Keywords: mucosal, respiratory, virus, clinical trial, immunology
Depositing User: Symplectic Admin
Date Deposited: 21 Nov 2019 14:27
Last Modified: 19 Jan 2023 00:19
DOI: 10.1164/rccm.201810-1921oc
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3062664
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