Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients

Abstract

Aims Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients. Methods and results A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness. Conclusions The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

The comparability of Anti-Spike SARS-CoV-2 antibody tests is time-dependent: a prospective observational study

“…The T-cellular activity was estimated in pre-and post-booster whole blood samples using the Quantiferon SARS-CoV-2 assay (Qiagen, Hilden, Germany [54][55][56] ). In brief, we quantified the interferon (IFN)γ-release after 21-hour incubation of 1 mL heparinized whole blood portions with two different SARS-CoV-2 antigen mixtures (Ag1, Ag2), and with a negative ("Nil") and a mitogen control, using an ELISA (Qiagen).…”

SARS-CoV-2 vaccination in cardiothoracic organ transplant recipients: effective strategies wanted

“…In contrast, humoral vaccination success (IgG antibodies and neutralizing antibodies) in healthy controls was seen in 49 subjects (98%) after the first vaccine dose, and in 100% after the second vaccine dose [9]. Additionally, healthy controls developed a significantly higher positive T-cell response (interferon-γ release) compared to transplant recipients (80% vs 16%) [9]. It is concluded that the BNT162b2 vaccine does not confer vaccination success against SARS-CoV-2 in the vast majority of cardiothoracic transplant recipients.…”

“…Antibody titers, functional inhibitory capacity of neutralizing antibodies, and T-cell response (interferon-γ release) were measured via three separate tests. Forty-six (92%) of the transplant recipients did not show any humoral or T-cell response 21 days after completion of the second vaccine dose [9]. In contrast, humoral vaccination success (IgG antibodies and neutralizing antibodies) in healthy controls was seen in 49 subjects (98%) after the first vaccine dose, and in 100% after the second vaccine dose [9].…”

“…Forty-six (92%) of the transplant recipients did not show any humoral or T-cell response 21 days after completion of the second vaccine dose [9]. In contrast, humoral vaccination success (IgG antibodies and neutralizing antibodies) in healthy controls was seen in 49 subjects (98%) after the first vaccine dose, and in 100% after the second vaccine dose [9]. Additionally, healthy controls developed a significantly higher positive T-cell response (interferon-γ release) compared to transplant recipients (80% vs 16%) [9].…”

“…In this issue of the Journal, Schramm and colleagues [9] report on a prospective cohort study of the immune response after administration of the BNT162b2 vaccine in 50 cardiothoracic (heart (n = 42), lung (n = 7) or heart-lung (n = 1)) transplant recipients from 5 German transplant centers 10-36 months after transplantation, compared to 50 healthy staff members similarly immunized with the same messenger RNA (mRNA) vaccine. Antibody titers, functional inhibitory capacity of neutralizing antibodies, and T-cell response (interferon-γ release) were measured via three separate tests.…”