Riste Michael, Marshall Julia L, Satti Iman, Harris Stephanie A, Wilkie Morven, Lopez Ramon Raquel, Wright Danny, Wittenberg Rachel E, Vermaak Samantha, Powell Doherty Rebecca, Lawrie Alison, Conlon Christopher P, Cosgrove Catherine, Gleeson Fergus, Lipman Marc, Moss Paul, Perrin Felicity, Dedicoat Martin, Bettinson Henry, McShane Helen
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
Department of Infection and Tropical Medicine, Heartlands Hospital, Birmingham B9 5SS, UK.
Vaccines (Basel). 2021 Apr 16;9(4):396. doi: 10.3390/vaccines9040396.
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 ( 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.
候选结核病（TB）疫苗MVA85A通过气溶胶给药可能会增强其免疫原性。皮内给药在潜伏性结核感染（LTBI）的成年人中已证明是安全的，但在该人群中，关于气溶胶递送候选结核病疫苗的数据尚缺乏。我们开展了一项I期试验，以评估在英国LTBI成年人中通过气溶胶递送MVA85A的安全性和免疫原性（NCT02532036）。招募了两名志愿者，疫苗耐受性良好，无安全问题。用MVA85A进行气溶胶疫苗接种可诱导血液中针对分枝杆菌和载体的干扰素-γ以及支气管肺泡灌洗中针对分枝杆菌的Th1细胞因子。我们确定了几个可能阻碍该患者群体进入临床试验的重要障碍。该试验未显示向两名英国LTBI成年人气溶胶递送候选病毒载体结核病疫苗存在任何安全问题。它还在气溶胶疫苗接种后全身性和黏膜性地证明了可诱导的免疫反应。在LTBI发病率较高的国家进行进一步试验将证实这些发现。
