Omicron BA.4/5 Neutralization and T-Cell Responses in Organ Transplant Recipients After Booster Messenger RNA Vaccine: A Multicenter Cohort Study

Pillar 4
Functional Genomics & Structure-Function of VOCs

Solid organ transplant recipients often become immunocompromised due to their treatment regimens. Susceptibility to more severe outcomes following COVID-19 infection in people who are immunocompromised, despite vaccination, is suggested to be partly due to suboptimal antibody-dependent neutralization of SARS-CoV-2 variants. Therefore, to provide protection against severe disease from COVID-19 that is comparable to that of healthy individuals, the primary COVID-19 vaccination series for solid organ transplant recipients consists of three doses followed by a booster.

We wanted to determine whether a bivalent booster as a 4^th dose could confer protection against Omicron BA.4/BA.5. To gauge immune protection, we collected blood samples from study participants at i) 4-6 weeks post third dose and ii) 4-6 weeks post fourth dose of mRNA vaccine. At these study timepoints, serum was isolated from whole blood to measure antibody neutralization, in an assay using virus-like particles coated with variant-specific Spike proteins. White blood cells isolated from whole blood from a subset of individuals was reserved for T-cell analysis.

We observed that participants who experienced a breakthrough infection prior to dose-4 were associated with greater neutralizing antibody responses compared to patients who received vaccination alone. We also found that low BA.4/BA.5 neutralization responses were associated with age, use of immunosuppressant drugs like mycophenolate and prednisone, vaccine type, and in particular lung transplantation. Furthermore, T-cell analysis showed that functional T-cell numbers increased after fourth dose. Overall, our study found that boosters increased T-cell responses and antibody neutralization of BA.4/BA.5. These increases in immune responses after boost may lead to protection from severe disease, even against Omicron variants. Despite the protection against variants that can come from receiving a booster, additional preventative strategies are still needed to protect solid organ transplant patients from COVID-19 infection who are older and/or receiving treatment with mycophenolate or prednisone.

Read article