Protective heterologous T cell immunity in COVID-19 induced by MMR and Tdap vaccine antigens.
Vijayashree MysoreXavier CullereMatthew L SettlesXinge JiMichael W KattanMichaël DesjardinsBlythe Durbin-JohnsonTal GilboaLindsey R BadenDavid R WaltAndrew LichtmanLara JehiTanya N MayadasPublished in: bioRxiv : the preprint server for biology (2021)
T cells are critical for control of viral infection and effective vaccination. We investigated whether prior Measles-Mumps-Rubella (MMR) or Tetanus-Diphtheria-pertussis (Tdap) vaccination elicit cross-reactive T cells that mitigate COVID-19. Using co-cultures of antigen presenting cells (APC) loaded with antigens and autologous T cells, we found a high correlation between responses to SARS-CoV-2 (Spike-S1 and Nucleocapsid) and MMR and Tdap vaccine proteins in both SARS-CoV-2 infected individuals and individuals immunized with mRNA-based SARS-CoV-2 vaccines. The overlapping T cell population contained effector memory T cells (TEMRA) previously implicated in anti-viral immunity and their activation required APC-derived IL-15. TCR- and scRNA-sequencing detected cross-reactive clones with TEMRA features among the cells recognizing SARS-CoV-2, MMR and Tdap epitopes. A propensity-weighted analysis of 73,582 COVID-19 patients revealed that severe disease outcomes (hospitalization and transfer to intensive care unit or death) were reduced in MMR or Tdap vaccinated individuals by 38-32% and 23-20% respectively. In summary, SARS-CoV-2 re-activates memory T cells generated by Tdap and MMR vaccines, which may reduce disease severity.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- induced apoptosis
- intensive care unit
- cell cycle arrest
- dendritic cells
- regulatory t cells
- single cell
- drug delivery
- magnetic resonance
- working memory
- bone marrow
- type diabetes
- endoplasmic reticulum stress
- stem cells
- coronavirus disease
- cell death
- early onset
- mass spectrometry
- signaling pathway
- case report
- high resolution
- cell proliferation
- cell therapy
- network analysis
- glycemic control