Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in lung transplant recipients

Abstract

The immunogenicity of the novel mRNA COVID-19 vaccine in immunocompromised lung transplant recipients is still unknown. We compared the antibody response after the first and second doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) with the response after natural SARS-CoV-2 infection in lung transplant recipients. None of the vaccinees tested after two doses of the mRNA BNT162b2 vaccine developed anti-SARS-CoV-2 IgG, while 85% patients presented an antibody response after SARS-CoV-2 infection. The absence of antibody response to vaccination led us to investigate the cellular response in a subset of patients. We detected SARS-CoV-2 specific T-cells in 4 out of 12 tested patients. Some patients therefore might have clinical benefit from the vaccine despite an absent antibody response. These results contrast with the excellent antibody response in immunocompetent individuals observed in mRNA BNT162b2 trials and indicate an urgent need to identify the best vaccine type and scheme for immunocompromised transplanted patients.

Keywords: COVID-19; antibody response; immunogenicity; lung transplantation; mRNA vaccine.

Figure 1

SARS-CoV-2-specific IgG response after BNT162b2 mRNA vaccine and SARS-CoV-2 Infection (A) SARS-CoV-2 spike S1 protein specific IgG detected by ELISA (B) SARS-CoV-2 IgG against a mix of recombinant antigens detected by Microblot-Array (C) SARS-CoV-2 specific IgG against trimeric spike S1 detected by CLIA. Vaccinated LTRs are evaluated at 4-6 weeks post 2nd dose (doses 3 weeks apart). LTRs post-COVID-19 were evaluated 3-6 weeks post onset. Healthy non-transplant vaccines were evaluated at median of 4 weeks (1-8 weeks). Significant difference (p < 0.001) is highlighted by a star. The dotted line shows the positivity threshold (the only value above the threshold in vaccinated LTR is considered false positive since it was not confirmed by the other two assays).

Figure 2

SARS-CoV-2 S-RBD specific response of CD4+ and CD8+ T cells. (A) A representative dot plot of flow cytometry measurement of IFN-γ producing CD4+ and CD8+ T cells (B) Twelve LTRs were assessed for SARS-CoV-2 S-RBD specific response of CD4+ and CD8+ T cells. Magnitude of the response is calculated as % of IFN-γ responding T-cells after S-RBD stimulation less % of IFN-γ without any stimulation.