There is evidence that MMR and Tdap vaccines may help protect against severe COVID-19, according to Twitter
Vaccines are designed to induce a strong and long-lasting immune response by producing memory T cells and B cells. The measles-mumps-rubella (MMR) vaccine, which is given in early childhood, and the tetanus-diphtheria-pertussis (Tdap) vaccine, which is given every 10 years, are known to induce a protective response against the diseases from which the vaccines get their name. But these vaccines can have an unexpected bonus: it’s possible that they also create cross-reactive memory T cells that are able to respond to protein targets called antigens that are present in other microbes that cause disease cause – including the viral antigens in SARS-CoV-2. The concept is that existing memory T cells, which were generated by a previous MMR or Tdap vaccination and activated by a SARS-CoV-2 infection, give the immune system a head start in responding to SARS-CoV- 2 and thereby the risk of severe COVID-19.
To investigate whether the MMR and Tdap vaccines offer additional protection against COVID-19, researchers at Brigham and Women’s Hospital performed laboratory-based analyzes using sensitive, new techniques to detect and characterize T cell responses to antigens. They used these techniques to analyze the response of T cells isolated from the blood of COVID-19 convalescent patients and patients vaccinated against COVID-19 to antigens of SARS-CoV-2 and the MMR and Tdap – Measure vaccines. Working with staff at the Cleveland Clinic, they also used a large, well-commented cohort of COVID-19 patients and found that previous MMR or Tdap vaccination was associated with decreased disease severity. Their results are published in Med.
“Our Cleveland Clinic colleagues observed an association where people with COVID-19 who had either MMR or Tdap vaccines went to intensive care or died much less often,” said co-author Andrew Lichtman, MD, PhD one Immunologist and Principal Investigator in Brigham’s Department of Pathology and Professor of Pathology at Harvard Medical School. “Although previous smaller studies suggested a similar association, our in-depth epidemiological analysis, along with our basic research, suggest that these commonly administered vaccines can protect against serious illness.”
“During the COVID-19 pandemic, we know that routine vaccinations for children and adolescents have decreased significantly,” said corresponding author Tanya Mayadas, PhD, senior researcher in Brigham’s Department of Pathology and professor of pathology at Harvard Medical School. “Our results underline the importance of routine vaccinations for children and adults. We know that vaccines protect against devastating diseases, and we are now seeing increasing evidence that some of them offer some protection against serious COVID-19 disease. “
The team’s investigation was triggered by an unexpected observation. Mayadas, her postdoctoral fellow Vijaya Mysore, PhD, and colleagues found in laboratory experiments with COVID-19 convalescent blood that whenever they observed an increased T cell response to SARS-CoV-2 proteins, also an increased response to proteins from MMR and Tdap, which they had used as controls. This has been observed in both COVID-19 convalescents and in uninfected individuals vaccinated against SARS-CoV-2. This connection was made through the team’s use of highly efficient antigen presenting cells (described in a recently published nature communication Paper) obtained from blood, loaded with SARS-CoV-2, MMR or Tdap antigens and cocultivated with T cells from the same individual. Using single cell RNA sequencing and analysis of T cell antigen receptors, the team observed that the antigen receptors on many of the T cells of people who had recovered from COVID-19 were linked to proteins from SARS-CoV-2 ( Spike-S1.) Responded and nucleocapsid) were identical to the antigen receptors on T cells that responded to MMR and Tdap proteins. This discovery indicated the presence of T cell clones that can respond to both SARS-CoV-2 antigens and the MMR and Tdap vaccine antigens.
In a second analysis, Mayadas and colleagues teamed up with investigators from the Cleveland Clinic to examine the epidemiological evidence. The Cleveland Clinic team conducted a retrospective cohort study of data from more than 75,000 patients seen in the Cleveland Clinic healthcare system in Ohio or Florida who tested positive for COVID-19 between March 8, 2020 and March 31, 2021 had been. The team used a statistical method known as overlap propensity score weighting to estimate two disease severity endpoints (COVID-related hospitalization and COVID-related ICU admission or death) for patients vaccinated against MMR or Tdap , and compare those who were not vaccinated. They found that patients previously vaccinated against MMR had a 38 percent decrease in hospital admissions and a 32 percent decrease in ICU admissions / deaths. Similarly, patients previously vaccinated against Tdap had 23 percent and 20 percent reduced rates of these results, respectively.
“In addition to learning the potential benefits of MMR and Tdap vaccines in the context of COVID-19, this study provides a blueprint for accelerating research,” said co-author Lara Jehi, MD, MHCDS, chief research information officer of the Cleveland Clinic Health system. “Laboratory-generated biomedical hypotheses can be explored through solid clinical and epidemiological research in well-curated, real-world data like the Cleveland Clinic’s COVID registry. The knowledge gained through this collaboration is much more than the sum of our individual parts. “
The authors note that while their laboratory-based results are bolstered by the epidemiological observations, more work is needed to assess the relationship between the MMR and Tdap vaccinations and the severity of COVID-19 disease to determine if the relationship is causal. Prospective studies of vaccinations and patient outcomes can help distinguish correlation from causality.
“With regard to COVID-19 vaccines, our results predict that MMR and Tdap, while not replacing COVID-19 vaccines, may offer greater and more permanent protection, possibly against emerging spike variants than the COVID-19- Vaccine alone, ”said Mayadas. “And in areas where the COVID-19 vaccines are not available, they could protect infected people from developing serious diseases.”
Conflict of Interest: Co-author David R. Walt has a financial stake in Quanterix Corporation, a company that develops a highly sensitive digital immunoassay platform. He is the inventor of Simoa technology, founder of the company and a member of the board of directors. The anti-SARS-CoV-2 Simoa tests in this publication have been licensed from Brigham and Women’s Hospital to Quanterix Corporation. Co-author Tal Gilboa receives royalties from Brigham and Women’s Hospital for antibody assay technology. Tanya Mayadas has a financial interest in neuAPC Therapeutics, a company that will develop anti-FcγRIIIB antibodies for the generation of neutrophil-derived antigen-presenting cells (nAPC) and will serve as one of its scientific advisors. Co-authors Vijayashree Mysore, Xavier Cullere and Mayadas hold a provisional patent on the generation of immunogenic nAPCs and methods of using them.
Financing: The work was supported by National Institutes of Health R01HL065095, R01AI152522, and R01NS097719, a generous donation from Barbara and Amos Hostetter and the Chleck Foundation.