This is a summary, written by members of the CITF Secretariat, of:

Dayam RM, Law JC, Goetgebuer RL, Chao GYC, Abe KT, Sutton M, Finkelstein N, Stempak JM, Pereira D, Croitoru D, Acheampong L, Rizwan S, Rymaszewski K, Milgrom R, Ganatra D, Batista NV, Girard M, Lau I, Law R, Cheung MW, Rathod B, Kitaygorodsky J, Samson R, Hu Q, Haroon N, Inman RD, Piguet V, Chandran V, Silverberg MS, Gingras AC, Watts TH. Antibody and T cell responses to SARS-CoV-2 mRNA vaccines during maintenance therapy for immune-mediated inflammatory diseases. medRxiv 2022.01.26.22269856; doi: https://doi.org/10.1101/2022.01.26.22269856

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

A recent pre-print, not yet been peer-reviewed, by CITF-funded researchers Drs. Anne-Claude Gingras, Tania Watts, and Vinod Chandran of the University of Toronto, studied the antibody and T-cell responses to SARS-CoV-2 mRNA vaccines in patients with a variety of immune-mediated inflammatory diseases (IMID) who were receiving immunomodulatory maintenance therapy. Most patients showed increased antibody and T cell responses after the first and second dose of mRNA vaccine, but those responses had significantly decreased three months after the second dose. The study provides evidence of the need for a third dose of mRNA vaccine and for continued monitoring of immunity over time in this patient population.

Key findings

  • Following the second dose of vaccine, 97% of participants had levels of anti-spike antibodies above the median of convalescent COVID-19 patients and 88.6% tested positive of anti-receptor-binding domain (RBD) antibodies. This response waned over time and, after three months, only 66.3% of participants tested positive for anti-spike antibodies, while 49.4% tested positive for anti-RBD antibodies.
  • Two doses of Moderna, or a mixed dosing of Moderna and Pfizer, elicited a more robust antibody response than two doses of Pfizer.
  • Participants on anti-TNF biologic therapy had lower anti-spike and anti-RBD antibodies levels than those in the healthy control group.
  • IMID patients undergoing anti-TNF therapy show significantly lower neutralization activity against the original SARS-CoV-2 virus and even less so against variants of concern (Alpha, Beta, and Delta). Their data also indicate that a subset of participants failed to neutralize the virus even with high anti-spike/RBD IgG levels in this group, suggesting they produced low affinity antibodies.
  • Combined analysis of all the study participants indicated an increase in T cell responses between the first and second doses, but these responses waned somewhat three months following the second dose.
  • The T-cell responses did not differ based on age or sex. All the participants in over the age of 60 exhibited a lower T cell responses after 2 doses of vaccine than younger subjects (??). The extent of T cell responses were positively correlatedPositively correlated means an increase in T-cell response is directly proportional to the increase in plasma antibodies and vice versa. with plasma antibodies against RBD and the whole spike molecule.

The study analyzed the antibody and T-cell responses in 150 participants at four time points – pre-vaccination, 2-4 weeks post-dose one, 2-4 weeks post-dose two, and 3 months after dose two. The median time interval between doses one and two was 60.5 days. Study participants suffered from a variety of conditions including: inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis or psoriatic disease, and were receiving immunomodulatory maintenance therapy either with biologics (anti-TNF, anti-IL-12/23, anti-IL-23, anti-IL-17) and/or anti-metabolites methotrexate/azathioprine (MTX/AZA). Due to the action of these drugs on the subjects’ immune systems, there was concern about whether they would mount responses to COVID 19 vaccines similar to healthy individuals. The results from the immune-deficit group were compared with nine patients with IMID not undergoing maintenance immune suppressive therapy and with 26 healthy individuals.

Overall, robust T cell responses were observed in most patients treated with immunosuppressants or biologics after one or two doses of mRNA vaccine; however, antibody levels and neutralization effectiveness in the anti-TNF treated group were lower than controls and waned substantially by three months post-dose two. These findings highlight the need for a third vaccine dose in IMID, particularly in patients undergoing treatment with TNF inhibitors.