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. 2021 Apr 16;9(4):396.
doi: 10.3390/vaccines9040396.

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

Michael Riste  1   2 , Julia L Marshall  1 , Iman Satti  1 , Stephanie A Harris  1 , Morven Wilkie  1 , Raquel Lopez Ramon  1 , Danny Wright  1 , Rachel E Wittenberg  1 , Samantha Vermaak  1 , Rebecca Powell Doherty  1 , Alison Lawrie  1 , Christopher P Conlon  3 , Catherine Cosgrove  4 , Fergus Gleeson  5 , Marc Lipman  6   7 , Paul Moss  8 , Felicity Perrin  9 , Martin Dedicoat  2 , Henry Bettinson  10 , Helen McShane  1
Affiliations

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

Michael Riste et al. Vaccines (Basel). .

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.

Keywords: MVA85A; aerosol vaccine; latent TB infection; mycobacteria.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
CONSORT flow diagram showing subject recruitment, follow-up, and reasons for exclusion.
Figure 2
Figure 2
IFNγ enzyme-linked immunospot (ELIspot) responses (A–C) or anti-r85A IgG levels (D). Frequency of antigen-specific IFN-γ ELISpot responses to (A) Ag85A, (B) purified protein derivative (PPD), and (C) antivector MVA CD4; (D) IgG levels against recombinant 85A in serum. x axis: time points in days; y axis: (A–C) spots per 1 × 106 PBMC, (D) absorbance at 405 nm. Circles and squares represent individual readings for two latently infected volunteers in this study, and triangles represent median readings for 10 healthy volunteers who received the same dose of aerosol MVA85A from our previous TB026 study [27].
Figure 3
Figure 3
Frequency of antigen-specific IFN-γ ELIspot responses to (A) MVA CD8, (B) ESAT-6, and (C) CFP-10 in two volunteers. x axis: timepoints in days; y axis: spots per 1 × 106 peripheral blood mononuclear cells.
Figure 4
Figure 4
Peripheral blood mononuclear cell (PBMC) intracellular cytokine staining (ICS). PBMC ICS antigen-specific responses in two latent Mycobacterium tuberculosis (M.tb)-infected UK adults vaccinated with 1 × 107 pfu aerosol-inhaled MVA85A. Percentages of CD4+ T cells producing IFN-γ, TNF-α, IL-2, IL-17, and CD8+ T cells producing IFN-γ and TNF-α in response to (A) Ag85A, (B) PPD, (C) ESAT-6, and (D) CFP-10. Individual values shown for each volunteer.
Figure 5
Figure 5
Bronchoalveolar lavage (BAL) intracellular cytokine staining (ICS) 7 days after aerosol MVA85A vaccination. BAL ICS antigen-specific responses in two latent Mycobacterium tuberculosis (M.tb)- infected UK adults vaccinated with 1 × 107 pfu aerosol-inhaled MVA85A. Percentages of CD4+ T cells producing IFN-γ, TNF-α, IL-2, IL-17, and CD8+ T cells producing IFN-γ and TNF-α in response to (A) Ag85A, (B) PPD, and (C) ESAT-6/CFP-10. Individual values shown for each volunteer.
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