Phase I Trial Evaluating the Safety and Immunogenicity of Candidate TB Vaccine MVA85A, Delivered by Aerosol to Healthy M.tb-Infected Adults

Michael Riste ,Helen Mcshane,Paul Moss,Iman Satti,Marc Lipman,Raquel Lopez Ramon,Morven Wilkie,Samantha Vermaak,Martin Dedicoat,Rachel Wittenberg,H Bettinson ,Rebecca Powell Doherty ,Felicity Perrin ,Catherine Cosgrove ,Fergus Gleeson ,Christopher P Conlon ,Julia Marshall ,Alison M Lawrie ,Daniel Wright ,Stephanie A Harris

doi:10.3390/vaccines9040396

Abstract

The immunogenicity of the candidate tuberculosis (TB) vaccine MVA85A may be enhanced by aerosol delivery. Intradermal administration was shown to be safe in adults with latent TB infection (LTBI), but data are lacking for aerosol-delivered candidate TB vaccines in this population. We carried out a Phase I trial to evaluate the safety and immunogenicity of MVA85A delivered by aerosol in UK adults with LTBI (NCT02532036). Two volunteers were recruited, and the vaccine was well-tolerated with no safety concerns. Aerosolised vaccination with MVA85A induced mycobacterium- and vector-specific IFN-γ in blood and mycobacterium-specific Th1 cytokines in bronchoalveolar lavage. We identified several important barriers that could hamper recruitment into clinical trials in this patient population. The trial did not show any safety concerns in the aerosol delivery of a candidate viral-vectored TB vaccine to two UK adults with Mycobacterium tuberculosis (M.tb) infection. It also systemically and mucosally demonstrated inducible immune responses following aerosol vaccination. A further trial in a country with higher incidence of LTBI would confirm these findings.

Highlights

Tuberculosis (TB) is the leading cause of death from a single infectious agent, with an estimated 10 million new cases and 1.4 million deaths in 2018 [1]
We previously demonstrated that intradermal MVA85A was well-tolerated and immunogenic in subjects with latent TB infection (LTBI) [28,29,30]
The primary objective was to evaluate the safety of MVA85A vaccination by the aerosolinhaled route in healthy volunteers latently infected with Mycobacterium tuberculosis (M.tb)

Summary

Introduction

Tuberculosis (TB) is the leading cause of death from a single infectious agent, with an estimated 10 million new cases and 1.4 million deaths in 2018 [1]. The development of a safe and effective TB vaccine is a key component of pillar 1 of the End TB strategy, which seeks to end the global TB epidemic [2]. The route of a Mycobacterium tuberculosis (M.tb) infection is by the inhalation of aerosolised infectious droplets, leading to primary infection in the lung and the development of a mucosal immune response [3,4]. In most people, this immune response contains the primary infection and results in latent infection, which carries a 5–10% lifetime risk of developing an active disease [1,5,6].

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Discussion

Conclusion