Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients

Abstract

Solid organ transplant recipients are at high risk of severe disease from COVID-19. We assessed the immunogenicity of mRNA-1273 vaccine using a combination of antibody testing, surrogate neutralization assays, and T cell assays. Patients were immunized with two doses of vaccine and immunogenicity assessed after each dose using the above tests. CD4+ and CD8+ T cell responses were assessed in a subset using flow-cytometry. A total of 127 patients were enrolled of which 110 provided serum at all time points. A positive anti-RBD antibody was seen in 5.0% after one dose and 34.5% after two doses. Neutralizing antibody was present in 26.9%. Of note, 28.5% of patients with anti-RBD did not have neutralizing antibody. T cell responses in a sub-cohort of 48 patients showed a positive CD4+ T cell response in 47.9%. Of note, in this sub-cohort, 46.2% of patients with a negative anti-RBD, still had a positive CD4+ T cell response. The vaccine was safe and well-tolerated. In summary, immunogenicity of mRNA-1273 COVID-19 vaccine was modest, but a subset of patients still develop neutralizing antibody and CD4+T- cell responses. Importantly polyfunctional CD4+T cell responses were observed in a significant portion who were antibody negative, further highlighting the importance of vaccination in this patient population. IRB Statement: This study was approved by the University Health Network Research Ethics Board (CAPCR ID 20-6069).

Keywords: clinical research/practice; infection and infectious agents - viral; infectious disease; vaccine.

FIGURE 1

Study flow [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Antibody titer in transplant recipients pre-/post-immunization with each dose of mRNA-1273 (Moderna) COVID-19 vaccine and convalescent titers of transplant recipients after COVID infection. Horizontal lines represent median and interquartile range. Dotted red line represents positive cut-off value of assay at 0.8 U/mI [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Surrogate Vaccine Neutralization Assay results in transplant recipients pre-/post-immunization with each dose of mRNA-1273 (Moderna) COVID-19 vaccine [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Cell-mediated immune response in transplant recipients pre-/post-immunization with each dose of mRNA-1273 (Moderna) COVID-19 vaccine. Horizontal lines represent median and range. Dotted line is the limit of quantitation (LOQ; 0.01% or 100 per 10⁶ cells). (A) Polyfunctional CD4+ T cell response. (B) Polyfunctional CD8+ T cell response [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 5

Local and systemic adverse effects within 7 days of mRNA-1273 COVID-19 vaccine in organ transplant recipients after the first and second doses (n = 108) [Color figure can be viewed at wileyonlinelibrary.com]