Gut microbiota: a new factor modulating the immunizing potential of viral and cancer vaccines.

Vaccines represent a major public health intervention against infectious diseases and potentially cancer. Surrogate markers of vaccine efficacy usually rely on neutralizing antibody titers afflicted by high interindividual variabilities. Automated multiplexed T cell assays currently allow to test the clinical relevance of T lymphocyte responses during vaccine rollout. We examined cellular and/or humoral immune responses in five independent cohorts of health care workers, young healthy individuals and patients with cancer (melanoma or lung cancer) receiving various immunizing formulations (non-replicating, viral/tumoral, mRNA/peptides/cellular/viral particles). Here we show that about 20% of vaccinees to non-replicating formulations fail to mount protective antibody and Th1/Tc1 responses while 9% receiving a live vaccine were hyperresponders. Vaccine outliers could at least in part be attributed to gut dysbiosis at baseline, evaluated by shotgun metagenomics-based machine learning or the TOPOSCORE. These findings highlight the requirement of diagnostic tools to identify intestinal dysbiosis, as well as microbiota-centered interventions to optimize the efficiency of mass vaccinations.