Airway surveillance and lung viral control by memory T cells induced by COVID-19 mRNA vaccine

Although SARS-CoV-2 evolution seeds a continuous stream of antibody-evasive viral variants, COVID-19 mRNA vaccines provide robust protection against severe disease and hospitalization. Here, we asked whether mRNA vaccine-induced memory T cells limits lung SARS-CoV-2 replication and severe disease. We show that mice and humans receiving booster BioNTech mRNA vaccine developed potent CD8 T-cell responses and show similar kinetics of expansion and contraction of granzyme B/perforin-expressing effector CD8 T cells. Both monovalent and bivalent mRNA vaccines elicited strong expansion of a heterogeneous pool of terminal effectors and memory precursor effector CD8 T cells in spleen, inguinal and mediastinal lymph nodes, pulmonary vasculature, and most surprisingly in the airways, suggestive of systemic and regional surveillance. Further, we document that: (1) CD8 T-cell memory persists in multiple tissues for >200 days; (2) following challenge with pathogenic SARS-CoV-2, circulating memory CD8 T cells rapidly extravasate to the lungs and promote expeditious viral clearance, by mechanisms that require CD4 T cell help; (3) adoptively transferred splenic memory CD8 T cells traffic to the airways, and promote lung SARS-CoV-2 clearance. These findings provide new insights into the critical role of memory T cells in preventing severe lung disease following breakthrough infections with antibody-evasive SARS-CoV-2 variants

Mycobacterium tuberculosis single nucleotide polymorphisms: endemic and epidemic isolates from RFLP types 0.0142 and 0.0728 in Alberta, Canada

Whole genome sequencing was performed on the Illumina HiSeq 2500. Paired-end reads were trimmed to remove adaptors and low-quality bases using Trim Galore v 0.2.6. We mapped reads to H37Rv (NC_000962.3) using BWA-MEM v 0.7.7. We used GATK v 2.8.1 for indel realignment and variant calling. We created SNP alignments from variant calls produced by reference guided assembly. SNPs falling in repetitive regions of the MTB genome (i.e. PE/PPE genes) and SNPs that corresponded to a gap or ambiguous call in other isolates were removed

Epidemiological and genomic determinants of tuberculosis outbreaks in First Nations communities in Canada

Abstract Background In Canada, tuberculosis disproportionately affects foreign-born and First Nations populations. Within First Nations’ peoples, a high proportion of cases occur in association with outbreaks. Tuberculosis transmission in the context of outbreaks is thought to result from the convergence of several factors including characteristics of the cases, contacts, the environment, and the pathogen. Methods We examined the epidemiological and genomic determinants of two well-characterized tuberculosis outbreaks attributed to two super-spreaders among First Nations in the province of Alberta. These outbreaks were associated with two distinct DNA fingerprints (restriction fragment-length polymorphisms or RFLPs 0.0142 and 0.0728). We compared outbreak isolates with endemic isolates not spatio-temporarily linked to outbreak cases. We extracted epidemiological variables pertaining to tuberculosis cases and contacts from individual public health records and the provincial tuberculosis registry. We conducted group analyses using parametric and non-parametric statistical tests. We carried out whole-genome sequencing and bioinformatic analysis using validated protocols. Results We observed differences between outbreak and endemic groups in the mean number of total and child-aged contacts and the number of contacts with new positive and converted tuberculin skin tests in all group comparisons (p < 0.05). Differences were also detected in the proportion of cases with cavitation on a chest radiograph and the mean number of close contacts in selected group comparisons (p < 0.02). A phylogenetic network analysis of whole-genome sequencing data indicated that most outbreak and endemic strains were closely related to the source case for the 0.0142 fingerprint. For the 0.0728 fingerprint, the source case haplotype was circulating among endemic cases prior to the outbreak. Genetic and temporal distances were not correlated for either RFLP 0.0142 (r 2  = − 0.05) or RFLP 0.0728 (r 2  = 0.09) when all isolates were analyzed. Conclusions We found no evidence that endemic strains acquired mutations resulting in their emergence in outbreak form. We conclude that the propagation of these outbreaks was likely driven by the combination of characteristics of the source cases, contacts, and the environment. The role of whole-genome sequencing in understanding mycobacterial evolution and in assisting public health authorities in conducting contact investigations and managing outbreaks is important and expected to grow in the future

Additional file 1: of Epidemiological and genomic determinants of tuberculosis outbreaks in First Nations communities in Canada

Table S1. Results of adjustment for multiple comparisons using a Benjamini–Hochberg procedure. (DOCX 15 kb