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

Background: The BNT162b2 mRNA vaccine (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, although with high between-subject variability. The humoral response wanes after 4-6 months from 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 yet clarified. Our aim was to evaluate the humoral and cell-mediated immune responses induced by the administration of the BNT162b2 vaccine after 6-8 months from the second dose in people with cystic fibrosis (pwCF) and the possible relationship between the anti-SARS-CoV-2 IgG-S antibodies (Spike protein) titer and the CD4 +/CD8 + cell-mediated response.

Methods: 113 pwCF (43 males, median age 21 years, 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 were determined by Elecsys® anti-SARS-CoV-2 S (Roche) enzyme immunoassay with cut off for positve respose at 0.8 U/mL; cell-mediated immune response was measured using the STANDARDTM F CoviFERON FIA (IFN-gamma) system, a new rapid Interferon Gamma Release Assay (IGRA), with cut off for positive response at 0.30 U/mL on standard F2400 (SD Biosensor, Inc. Korea).

Results: All patients showed a humoral response 6-8 months after the second vaccine dose, with a median antibody titer of 1288 U/mL (interquartile range, IQR: 610-2397). pwCF who were previously infected by SARS-CoV-2 had higher antibody titer as compared to those naïve to the virus (median 6302, IQR: 4272-8349 vs 1180, IQR: 535-1742, P< 0.0001). Sixty-one patients (54%) developed a cell-mediated immune response against SAR-CoV-2. Antibody titer was higher among patients who showed a positive cell-mediated response as compared to those who did not (median, IQR: 1453, 778-4473 vs 1054, 510-1498, P= 0.010).

Conclusions: All patients developed an adequate humoral response following two doses of BNT162b2 vaccine; the antibody titer was higher in patients with previous SARS-CoV-2 infection than in naive patients. We could document a cell-mediated response only in 54% of patients and this was associated with a higher antibody titer. Further studies are needed to understand whether the development of cell-mediated immune response is elated with increased protection against severe Covid-19 in pwCF. If this would be the case, this rapid and relatively inexpensive test may be a useful tool to recognize the timing of additional vaccine doses in this clinically vulnerable population.

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