Distinct immunological and molecular signatures predict influenza vaccine responsiveness in the elderly (scRNA Seq)

The significant economic burden and high mortality rates resulting from seasonal influenza outbreaks, especially in high risk groups such as the elderly, represent an important public health problem. The prevailing inadequate efficacy of seasonal vaccines, both conventional and elderly-tailored, is a crucial bottleneck. Consequentially, understanding immunological and molecular mechanisms resulting in differential influenza vaccine responsiveness is a prerequisite for the development of new or improved vaccination strategies. To assess differences within the specific risk group of the elderly, randomly selected individuals (= 65 years) were immunized with the adjuvanted influenza vaccine Fluad®. Samples were subjected to single cell transcriptome analysis. The analyses revealed profound features segregating vaccine responders from nonresponders as classified according to their vaccine-induced sero-conversion. Non-responders are characterized by a poorly functional, suppressive phenotype, showing a weaker humoral and cellular immune activation and more suppressive regulatory T and B cells. Triple responders display an efficient immune functionality characterized by the activation of humoral and cellular immunity and the up-regulation of genes related to signaling pathways, including those for anti-viral responses, protein processing and B cell activation. The generated comprehensive high dimensional dataset enables the identification of putative mechanisms and nodes responsible for vaccine non-responsiveness regardless of confounding age-dependent effects. Overall design: For the single cell transcriptome analysis, PBMCs isolated from whole blood samples were used. Analysis compares the effect of vaccination among two groups classified as vaccine responders ( R ) and vaccine non responders (NR) after 7 days post vaccination. Each group is represented by three donors ( NR: I-0845, I-4236, I-4964; R: I-4229, I-5127,I-5402 )