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

Ferreira VH, Ierullo M, Mavandadnejad F, Kurtesi A, Hu Q, Hardy WR, Hall VG, Pinzon N, Yotis D, Gingras AC, Belga S, Shalhoub S, Hébert MJ, Humar A, Kabbani D, Kumar D; PREVenT Study Group. Omicron BA.4/5 neutralization and T-cell responses in organ transplant recipients after Booster mRNA vaccine: a Multicenter Cohort Study. Clin Infect Dis. 2023 Mar 28:ciad175. doi: 10.1093/cid/ciad175.

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 Clinical Infectious Diseases, reported that a fourth vaccine dose significantly increases BA.4/5-specific neutralizing antibodies, as well as CD4+ T cell responses in solid organ transplant recipients (SOTR). This suggests protection against severe disease from the most recent Omicron variants. However, SOTR who are older, recipients of lung transplants, or are taking mycophenolate or prednisone, may need additional preventative strategies. The study was led by Dr. Deepali Kumar (University Health Network, Toronto).

Key findings:

  • Neutralizing antibodies directed against Omicron BA.4/5 increased from 26.6% (59/222) after the third dose to 53.6% (119/222) after the fourth dose.
  • However, nearly half of all SOTR did not generate neutralizing responses to these subvariants. Factors associated with absence of BA.4/5 neutralization response after a fourth dose included:
    • older age (odds ratio [OR] 0.96),
    • mycophenolate (OR 0.39) or prednisone use (OR 0.34), and
    • having received the Pfizer-BioNTech vaccine for all four doses (OR 0.72).
  • Lung transplant recipients had the lowest antibody responses following booster vaccination. This may be due to the overall increased level of immunosuppressive treatment used for people with this transplant type.
  • Breakthrough infections occurred in 42 SOTR (18.9% of the cohort). Most breakthrough cases were detected after the third dose (27/42, 64.3%) and the remainder after the fourth dose.
  • Most SOTR who had a breakthrough infection after the third dose, but prior to fourth dose (24/27), did not have detectable neutralizing antibodies prior to their COVID-19 diagnosis. In these patients, neutralization increased to 77.8% (21/27) after their fourth dose.
  • The median neutralizing antibody level in participants with hybrid immunity (infection + 4 doses) was significantly higher compared to those with four vaccine doses alone.
  • Polyfunctional BA.4/5-specific CD4+ T-cells significantly increased after four doses and were identified in 76.9% of these

Whole blood serum was collected 4-6 weeks after both the third and the fourth dose of mRNA vaccine in 222 SOTRs. The median age of the cohort was 63 years and 61.7% of the participants were men.