Protective heterologous T cell immunity in COVID-19 induced by MMR and Tdap vaccine antigens

Abstract

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.

Vaccination history for diphtheria and tetanus is associated with less severe COVID-19

“…In line with our a priori hypothesis, and replicating recent findings, 17 our results indicate that DTP vaccinations explain variation in the clinical profile of individuals with exposure to the SARS-CoV-2 virus. Our findings seem to suggest that particularly diphtheria and/or tetanus vaccinations may protect against the development of severe COVID-19 symptoms.…”

“…10,15,16 This is supported by one recent study showing a strong correlation between SARS-CoV-2 response and DTP vaccine proteins. 17 The potential protective effects were most evident in the analyses of COVID-19 severity, yet they may also explain more subtle differences in testing and test outcomes between those with and without these vaccinations by suppressing mild symptoms, thereby influencing who shows up for testing.…”

“…Further, while we excluded individuals with the BCG vaccine based on its suspected relation with COVID-19 severity, some additional vaccines that were contrasted to the DTP vaccines, e.g. for Measles or Hepatitis B, 12,14,17 can potentially have protective effects on COVID-19 symptom presentation as well, thereby obscuring even greater effects of tetanus and/or diphtheria vaccination. It will therefore be important to explore the potential effects of individual vaccines in greater detail, and with more controlled comparison groups.…”

“…In this same study, severe disease outcomes were reduced among DTP vaccinated COVID-19 patients. 17 Together, these clues, coming independently from researchers with distinct backgrounds and with different methodologies, provide an intriguing possibility that DTP vaccinations may explain part of the clinical variability of COVID-19 by modulating the immune response.…”

COVID-19 Convalescent Plasma Is More than Neutralizing Antibodies: A Narrative Review of Potential Beneficial and Detrimental Co-Factors

“…MMR (measles-mumps-rubella) or Tdap (tetanus-diphtheria-acellular pertussis) vaccination [46]. Of interest, the SARS-CoV-2 spike protein displays biologically significant amino acid sequence similarities with paramyxovirus surface proteins [47].…”