Pillar 4
Functional Genomics & Structure-Function of VOCs

Immune mediated inflammatory diseases (IMID), such as arthritis, inflammatory bowel diseases and severe inflammatory skin diseases such as psoriasis and hidradenitis suppurativa are often treated with systemic medication or biologics that can reduce inflammation. There has been concern that these treatments might decrease the immune response to vaccines for protection against SARS-CoV-2, the virus that causes COVID-19.

To determine if this is the case, scientists located at the University of Toronto, University Health Network, Sinai Health and Women’s College Hospital in Toronto followed a group of 150 people including 26 healthy controls and 124 IMID patients who were untreated or undergoing therapy with one of several different immune modulating drugs. Blood samples were collected before the first mRNA vaccine dose as well as after the first and 2nd dose of vaccine and 3 months after the 2nd dose.

The blood was used to isolate plasma to measure antibodies and cells to analyze T cells. T cells are a kind of white blood cell that is important in clearing up a virus infection, particularly if any of the virus gets past our antibody defenses. T cells also help B cells to make stronger and more abundant antibodies. The study analyzed the ability of T cells to be activated when they were exposed to Spike fragments as well as the amount of antibodies in the samples that could bind the SARS-CoV-2 Spike protein. The study also measured the ability of these antibodies to “neutralize” the virus. To do this, the scientists used a synthetic virus, containing SARS-CoV-2 Spike and measured whether the study subjects’ antibodies could prevent the virus getting into cells. The study showed that there was an increase in antibody and T cell responses in all groups of study subjects after 1 or 2 doses of an mRNA vaccine.

In general, antibody and T cell responses were lower the IMID patients after 1 dose of vaccine, but the 2nd dose brought up the response of most of the IMID group to that of healthy controls. However, the antibody and T cell responses of the IMID patients decreased more rapidly by 3 months after second dose compared to the healthy controls. Of note, patients treated with anti-TNF agents, such as infliximab, adalimumab or etanercept, had lower antibody responses than healthy controls even after 2 doses of vaccine, and their antibodies were weaker at blocking virus entry into cells.

Importantly, the study showed that the antibodies taken from the anti-TNF treated patients at 3 months after the 2nd vaccine dose had no ability to block the Omicron variant. The study also showed that the participants who received two doses of the Moderna vaccine or a mixed dose (Pfizer/Moderna or Moderna/Pfizer) had higher T cell and antibody responses than those receiving two doses of Pfizer vaccine.

The results reported in this study suggest that a 3rd dose of vaccine is very important in IMID patients. The findings also suggest that the higher dose Moderna vaccine may be preferred for immunocompromised people. Further work is ongoing to look at the effect of 3rd and 4th doses in these patients and to determine how long these responses last.   Funding for this study came from Juan and Stefania Speck, the Canadian Institutes of Health Research, the COVID Immunity task force and COVARR-Net.

Roya M. Dayam, Jaclyn C. Law, Rogier L. Goetgebuer, Gary Y.C. Chao, Kento T. Abe, Mitchell Sutton, Naomi Finkelstein, Joanne M. Stempak, Daniel Pereira, David Croitoru, Lily Acheampong,7 Saima Rizwan, Klaudia Rymaszewski, Raquel Milgrom, Darshini Ganatra, Nathalia V. Batista, Melanie Girard, Irene Lau, Ryan Law, Michelle W. Cheung, Bhavisha Rathod, Julia Kitaygorodsky, Reuben Samson, Queenie Hu, W. Rod Hardy,1 Nigil Haroon, Robert D. Inman, Vincent Piguet, Vinod Chandran, Mark S. Silverberg, Anne-Claude Gingras, and Tania H. Watts. Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases. JCI Insight. 2022;7(11):e159721. https://doi.org/10.1172/jci.insight.159721