Humoral and Cell-mediated Immune Response to the SARS-CoV-2 Vaccine in Immunocompetent and Immunocompromised Subjects: An Observational, Longitudinal, Prospective Study

Background: the emergence of SARS-CoV-2 in late 2019 has led to the rapid development of protective vaccines, the first of which to receive approval for use was the mRNA vaccine developed by Pfizer/BioNTech (BNT162b2). Safety and efficacy trials focused on the healthy population, yet real-world vaccination campaign strategies prioritised at-risk populations, among which are patients receiving immunosuppressive therapy for autoimmune conditions and against post-operative transplant rejection, and oncologic patients. Materials and Methods: measurements of serum SARS-CoV-2-specific anti-Spike IgG antibodies, titres of SARS-CoV-2-specific neutralising antibodies, and ELISpot assays for IFN-γ-producing, SARS-CoV-2-specific T-cells were performed on samples from 119 healthy healthcare workers, 123 patients with autoimmune conditions, 82 solid-organ transplant recipients, and 40 oncologic patients. The samples were taken on the day of the first vaccine dose (day 1; time 0), before the second dose (day 22; time 1), 21 days after the second dose (day 43; time 2), and at the 6 months mark (time 3). All subject groups were sub-divided to virus-naïve and virus-experienced individuals. Results: all immunocompetent subjects had a positive humoral and cell-mediated response to the vaccines. In the neoplasm group the response was comparable to the immunocompetent group, and in both immunocompetent controls and neoplasm groups receiving immune checkpoint inhibitors (ICIs) the waning of the antibody levels at time 3 was more accentuated for the virus-naïve subjects. Regarding the transplant group, it may generally be stated that the humoral response of the experienced transplant group was comparable to that of the experienced controls, while the humoral and T-cell responses of the naïve transplant group were significantly reduced. In the autoimmune group, the analysis of the naïve group showed an overall decreased cellular response compared to controls, while the humoral response within the group showed a high degree of variability, likely due to the high variability of the therapeutic regiments within this group. Finally, the humoral response appeared dependent on a positive cellular response. Conclusions: the results of this analysis suggested that the different categories of immunosuppressed patients have a variable degree of responsiveness to the mRNA vaccine. Due to the T-cell dependence of the antibody response, the potential development of the humoral response after the booster dose could be anticipated on the basis of ELISpot measurements. This could present a consideration for future efforts of booster vaccinations in the autoimmune patient population. The analysis further suggests that a proportion of solid-organ transplant recipients can mount an effective T-cell response within 6 months from the first dose, but to a lesser degree than immunocompetent subjects, representing a consideration for clinicians when discussing post-vaccination risk management with patients, or informing them about the potential effectiveness of a booster dose. In the oncologic patient group receiving ICIs, the analysis suggested a possible advantage for long-term humoral convalescence. This is likely to result from the therapy with ICIs, which leads to higher-than-normal T-cell titres, which are then conducive to a more robust and sustained humoral response.