Humoral and cell-mediated responses to BNT162b2 mRNA vaccine against SARS-CoV-2 in people with cystic fibrosis

ABSTRACT

Background: The BNT162b2 mRNAvaccine (Pfizer-BioNTech) was the first anti-SARS-CoV-2 vaccine approved and has shown 95% efficacy against severe COVID-19. The vaccine elicits a combined humoral and cellular adaptive immune response, albeit with high between-subject variability. The humoral response wanes 4 to 6 months after vaccination and, considered alone, does not appear to be indicative of protective immune memory. The role of cell-mediated immune response, which may be more relevant in the long-term protection against SARS-CoV-2, has not been clarified. Our aim was to evaluate the humoral and cell-mediated immune responses induced by administration of the BNT162b2 vaccine 6 to 8 months after the second dose in people with cystic fibrosis (PwCF) and the possible relationship between the anti-SARS-CoV-2 immunoglobulin (Ig)G-S antibodies (Spike protein) titer and the CD4+/CD8+ cell-mediated response. Method(s) One hundred thirteen PwCF (43 male, median age 21, range 11- 64) were enrolled, including 12 patients with virologically confirmed prior SARS-CoV-2 infection. Patients receiving chronic steroid therapy and transplant recipients were excluded. Serum IgG-S was determined by Elecsys anti-SARS-CoV-2 S (Roche) enzyme immunoassay with cut-off for positive response at 0.8 U/mL;cell-mediated immune response was measured using the STANDARDTM F CoviFERON FIA (interferon-gamma) system, a newrapid interferon gamma release assay (IGRA),with cut-off for positive response at 0.30 U/mL on standard F2400 (SD Biosensor, Inc. Korea). Result(s) All patients showed a humoral response 6 to 8 months after the second vaccine dose, with a median antibody titer of 1,288 U/mL (interquartile range [IQR] 610-2397). PwCF who were previously infected by SARS-CoV-2 had higher antibody titers than those naive to the virus (median 6,302, IQR 4272-8349 vs 1,180, IQR 535-1742;p < 0.001). Sixtyone patients (54%) developed a cell-mediated immune response against SARS-CoV-2. Antibody titer was higher in patients with a positive cellmediated response (median 1453, IQR 778-4473) than in those without (median 1054, IQR 510-1498) ( p = 0.01). Conclusion(s) All patients developed an adequate humoral response after two doses of BNT162b2 vaccine;the antibody titer was higher in patients with previous SARS-CoV-2 infection than in naive patients. We documented a cell-mediated response in 54% of patients, and this was associated with a higher antibody titer. Further studies are needed to understand whether development of cell-mediated immune response is elicited with greater protection against severe COVID-19 in PwCF. If this were the case, this rapid and relatively inexpensive test might be a useful tool to determine the best timing for additional vaccine doses in this clinically vulnerable population. Copyright © 2022, European Cystic Fibrosis Society. All rights reserved