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.

Keywords: BioNTech/Pfizer (BNT162b2) vaccine; Covid-19 infection; Immunocompromised patients; Immunogenicity; Transplant recipients.

Fig. 1

Serological responses to BNT162b2 vaccination in transplant recipients and healthy controls (n = 50 each): IgG-Antibodies. Samples drawn 21 days after the prime (blue dots) and the booster dose (orange dots). Scatter plots show: A Anti-SARS-CoV-2 IgG, given in binding antibody units per ml ([BAU/ml]; Abbott). B Anti-SARS-CoV-2 IgG, given in Units per ml ([U/ml]; RocheElecsys). C Anti-SARS-CoV-2 IgG, given in Relative Units per ml [(RU/ml); Euroimmun]. Statistical analysis was by Mann–Whitney Test. Horizontal solid lines show Medians. Horizontal dotted lines show cut-off values according to manufacturers. ns non-significant, IgG immunoglobulin G

Fig. 2

Serological responses to BNT162b2 vaccination in transplant recipients and healthy controls (n = 50 each): Inhibitory capacity of neutralizing antibodies. Samples drawn 21 days after the prime (blue dots) and the booster dose (orange dots). Scatter plots show inhibition in %. Statistical analysis was by Mann–Whitney Test. Horizontal solid lines show Medians. Horizontal dotted lines show cut-off values according to manufacturer (Genscript). Ns non-significant

Fig. 3

Specific T-cell response as stimulated IFN-γ release. Samples drawn 21 days after the booster dose. Scatter plots show Interferon γ (IFN-γ) release after stimulation with SARS-CoV-2 specific peptides (Miltenyi Biotec), given in International Units per ml [IU/ml]. Statistical analysis was by (Mann–Whitney Test). Horizontal lines show Medians. ns non-significant