This is a summary, written by members of the CITF Secretariat, of:
Halvorson T, Ivison S, Huang Q, Ladua G, Yotis DM, Mannar D, Subramaniam S, Ferreira VH, Kumar D, Belga S, Levings MK. SARS-CoV-2 variants Omicron BA.4/5 and XBB.1.5 significantly escape T cell recognition in solid organ transplant recipients vaccinated against the ancestral strain. medRxiv 2023.08.14.23293991; doi: https://doi.org/10.1101/2023.08.14.23293991
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A CITF-funded study, published in preprint and not yet peer-reviewed, found that vaccination induced robust SARS-CoV-2-specific T-cells responses against Omicron variant BA.4/5, in solid organ transplant recipients (SOTRs). These responses remained detectable over time and further increased following a fourth dose. SOTRs also showed better T-cell responses against Omicron variant XBB.1.5 after three ancestral strain monovalent vaccine doses. However, responses to Omicron BA.4/5 and XBB.1.5 were significantly lower in magnitude compared to ancestral strain responses after three doses of the original monovalent mRNA vaccine. The study was led by Drs. Megan Levings and Sara Belga (both from University of British Columbia) in collaboration with Dr. Deepali Kumar (University Health Network) on behalf of the PREVent study group.
- Vaccination induced SARS-CoV-2-specific T cell responses against Omicron variants BA.4/5 and XBB.1.5. T cell responses were further increased against Omicron BA.4/5 after a fourth mRNA vaccine dose (the T cell responses to XBB.1.5 were not tested after a fourth dose).
- However, after three ancestral strain vaccine doses, CD4+ T cell responses to Omicron BA.4/5 and XBB.1.5 were significantly lower in magnitude than responses to the ancestral strain. Similar trends were observed among CD8+ T cells.
- SOTRs who received a fourth vaccine dose and/or those with hybrid immunityReceived a fourth dose and contracted COVID-19 showed an increase in T cell responses, above post-third dose levels, against the ancestral strain and against Omicron variant BA.4/5. These increases were significantly greater than those in controls who did not receive a fourth dose and who had not contracted SARS-CoV-2. No significant differences were identified between the fourth dose and hybrid immunity groups.
- Antigen-specific CD4+ T cell frequencies correlated with anti-receptor binding domain (RBD) antibody titres. This correlation was enhanced by a third dose, for responses to both the ancestral strain and BA.4/5.
- Patients receiving prednisone, lung transplant recipients, and older adults displayed weaker T cell responses.
The study cohort consisted of 42 SOTRs with a median age of 58 years, of whom 22 (52%) were female and 20 (48%) were male. Subjects were recipients of kidney (n = 16), liver (n = 16), or lung (n=10) transplants. Median time since transplantation was 6.8 years. All subjects received at least two doses of monovalent Pfizer or Moderna ancestral strain mRNA COVID-19 vaccines. As one-year samples were collected soon (3-6 weeks) after patients received a fourth dose, subjects were grouped as having neither contracted SARS-CoV-2 nor received a fourth dose (controls, n=6), post-fourth dose (n=15), post-fourth dose and contracted SARS-CoV-2 (hybrid, n=7), or contracted SARS-CoV-2 infection only (n=4). At enrolment, all patients were receiving at least one immune-suppressive drug, with tacrolimus (35/42, 83%), mycophenolate mofetil or mycophenolate sodium (27/42, 64%), and prednisone (20/42, 48%) being the most frequent.