Solid organ transplant recipients (SOTRs) face profound disturbances to their immune system due to prolonged exposure to immunosuppressive drugs, which make them generally more susceptible to infections such as SARS-CoV-2. Data shows that nearly 78% of transplant patients affected by COVID-19 required hospitalization and up to 30% may succumb to infection.1

CITF-funded researcher Dr. Deepali Kumar and her team from the University Health Network in Toronto have published a number of articles evaluating immune responses to SARS-CoV-2 infection and vaccination in this vulnerable population2,3,4.

Key points:

  • Majority of SOTRs mount cell-mediated and humoral immune responses following SARS-CoV-2 infection. However, mRNA vaccines may induce lower levels of polyfunctional IFN-g+ IL-2+ T cells compared to SARS-CoV-2 infection.
  • A randomized double-blind study conducted in 120 SOTRs who received two doses of the Moderna mRNA vaccine demonstrated that an additional booster (3rd dose) can be safe and effective at enhancing protective anti-RBD antibodies.
  • This booster dose was also found to be effective at significantly increasing the levels of protective neutralizing antibodies against SARS-CoV-2, including variants such as Alpha, Beta and Delta. This research was done prior to the arrival of Omicron.

A number of studies have demonstrated that the standard two-dose vaccine regimen may induce suboptimal immune protection against SARS-CoV-2 in SOTRs5,6,7. Dr. Kumar’s group evaluated T cell immune responses to SARS-CoV-2 infection among kidney, liver, heart and lung transplant patients, and compared them to the responses observed in non-transplant controls2, finding that the majority of SOTR patients need further follow-up to ensure adequate protection against breakthrough infections post-vaccination.

While two doses of vaccines are sufficient to induce robust immune responses in the general population, the immune perturbations in SOTRs may be associated with more severe breakthrough infections.  Hence, to understand, before Omicron, whether a third dose may be helpful for this cohort, Hall V.G. et al published a randomized double-blind clinical trial with 120 SOTRs who received two doses of the Moderna Cominarty vaccine and evaluated whether a third dose can significantly enhance anti-SARS-CoV-2 responses3. The researchers demonstrated that a third dose induced a significant increase in anti-RBD antibodies and SARS-CoV-2-specific CD4+ T cell responses compared to the placebo treatment. While the trial was not performed to evaluate overall differences in clinical efficacy, a third dose was deemed to be safe and effective at further enhancing SARS-CoV-2 antiviral immunity amongst SOTRs.

Dr. Kumar’s team also evaluated the functional ability of antibodies generated following two or three doses of vaccine to neutralize different variants (Alpha, Beta, Delta) among SOTRs. They found that a third (booster) dose was effective at significantly increasing neutralizing antibodies against SARS-CoV-2 and its variants.

Their work has demonstrated the importance of considering the unique requirements of different populations, such as immunocompromised individuals, when determining immunization recommendations.

References:

  • Pereira MR, Arcasoy S, Farr MA, Mohan S, Emond JC, Tsapepas DS, Shi Q, Purpura L, Uhlemann AC, Zucker J, Verna EC. Outcomes of COVID‐19 in solid organ transplant recipients: A matched cohort study. Transplant Infectious Disease. 2021 May 16:e13637.
  • Ferreira VH, Marinelli T, Ierullo M, Ku T, Hall VG, Majchrzak-Kita B, Kulasingam V, Humar A, Kumar D. Severe Acute Respiratory Syndrome Coronavirus 2 Infection Induces Greater T-Cell Responses Compared to Vaccination in Solid Organ Transplant Recipients. The Journal of infectious diseases. 2021 Dec 1;224(11):1849-60.
  • Hall VG, Ferreira VH, Ku T, Ierullo M, Majchrzak-Kita B, Chaparro C, Selzner N, Schiff J, McDonald M, Tomlinson G, Kulasingam V. Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients. New England Journal of Medicine. 2021 Sep 23;385(13):1244-6.
  • Kumar D, Ferreira VH, Hall VG, Hu Q, Samson R, Ku T, Ierullo M, Majchrzak-Kita B, Tomlinson G, Gingras AC, Humar A. Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine: Secondary Analysis of a Randomized Trial. Annals of internal medicine. 2021 Nov 23.
  • Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204-6. [PMID: 33950155] doi:10.1001/jama.2021.7489
  • Hall VG, Ferreira VH, Ierullo M, et al. Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients. Am J Transplant. 2021.[PMID: 34347934] doi:10.1111/ajt.16766
  • Stumpf J, Siepmann T, Lindner T, et al. Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: a prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine. Lancet Reg Health Eur.2021;9:100178. [PMID: 34318288] doi:10.1016/j.lanepe.2021.100178