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

Cheung MW, Dayam RM, Shapiro JR, Law JC, Chao GYC, Pereira D, Goetgebuer RL, Croitoru D, Stempak JM, Acheampong L, Rizwan S, Lee JD, Jacob L, Ganatra D, Law R, Rodriguez-Castellanos VE, Kern-Smith M, Delgado-Brand M, Mailhot G, Haroon N, Inman RD, Piguet V, Chandran V, Silverberg MS, Watts TH, Gingras AC. Third and fourth vaccine doses broaden and prolong immunity to SARS-CoV-2 in immunocompromised adult patients. medRxiv 2023.03.01.23286513; doi:

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

A CITF-funded study, published in preprint and not yet peer-reviewed, demonstrates that third and fourth doses of vaccine sustain and broaden immune responses to SARS-CoV-2 in adults with immune-mediated inflammatory diseases (IMIDs). The authors conclude that this supports the recommendation for three- and four-dose primary series vaccine regimens in this population. The research is a collaboration between CITF-funded researchers Drs. Vinod Chandran, Tania Watts, and Anne-Claude Gingras (University of Toronto), and colleagues Drs. Vincent Piguet and Mark Silverberg.

Key findings:

  • Three to four months after a second vaccine dose, IMID patients had significantly reduced SARS-CoV-2 specific antibodies, neutralization, and T cell responses, A third dose was critical for boosting these responses to levels similar to healthy controls.
  • IMID patients, as a whole, reached the same peak antibody responses as healthy controls. However, patients on anti-TNF therapy consistently showed reduced RBD- and spike-specific levels compared to healthy controls or non-anti-TNF treated IMID patients. This held true from the first to the fourth dose of vaccine.
  • Third and fourth doses of vaccine enhanced the duration of antibody responses to SARS-CoV-2 in IMID patients.
  • Third doses were found to be important in both healthy controls and IMID patients for reducing the decay of neutralization responses to all variants of SARS-CoV-2, thereby broadening neutralization activity. Fourth doses showed additional stabilizing effects in IMID patients.
  • T cell responses in IMID patients to the wild-type virus, as well as to the BA.1 and BA.5 Omicron subvariants, were largely equivalent after three vaccine doses. There were no differences observed in anti-TNF and non-anti-TNF-treated patients.

161 participants contributed 607 samples to the study over eight time points beginning in January 2021. They were diagnosed with one or more IMIDs, were either untreated or treated with maintenance immunosuppressive therapy, and received a SARS-CoV-2 mRNA vaccine. Healthy controls were included only up to three months post-dose three. Most study subjects received the Pfizer vaccine.