Background Very few cancer patients were enrolled in COVID-19 vaccine studies. In order to address this gap of knowledge, real world studies are mandatory. Aim of this study was to assess both humoral and cellular response after a mRNA vaccination schedule. Patients and methods Eighty-eight consecutive cancer patients treated with PD-1/PD-L1 inhibitors were enrolled from the beginning of the vaccination campaign for frail patients. Blood samples for humoral and cell-mediated immune response evaluation were obtained before vaccination (T0), before the second administration (T1) and 21 days after the second dose (T2). The primary end-point was the evaluation of the percentage of participants showing a significant increase in SARS-CoV-2 specific T cells, measured by an ELISPOT assay, after the second dose of BNT162b2 vaccine. The proportion of patients who reached the primary endpoint is computed together with its exact binomial 95% confidence interval (95%CI). Results In SARS-CoV-2 naïve subjects, Spike-specific T-cell response was almost undetectable at T0 (median 0.0 IFNγ SFU/million PBMC IQR 0-7.5) and significantly increased at T1 and T2 (median 15.0 IFNγ SFU/million PBMC 25th-75th 0-40 vs 90 IFNγ SFU/million PBMC 25th-75th 32.5-224; respectively) (p<0.001). Focusing on naïve and experienced SARS-CoV-2 subjects no differences were reported both in terms of CD4 and CD8-specific T-cell response, suggesting that BNT162b2 is able to elicit both adaptive responses after complete vaccination schedule, regardless previous SARS-CoV-2 exposure. The level of SARS-CoV-2 NT Abs was low at T1 in SARS-CoV-2 naïve subjects [median 1:5 (IQR 1:5-1:20)] but reached a significantly higher median 1:80 (25th-75th 1:20-1:160) at T2 (p<0.0001). Moreover no COVID-19 cases were documented throughout the period of study. Conclusions Our data have demonstrated that the administration of a full course of BNT162b2 vaccine elicited a sustained immune response against SARS-CoV-2 regardless to the type of cancer and/or the type of ICIs.

Objectives To assess SARS-CoV-2 humoral and cell-mediated response elicited by mRNA BNT162b2 vaccine in SARS-CoV-2 experienced and naïve subjects against reference strain and SARS-CoV-2 variants. Methods Humoral response, including neutralizing antibodies, and T-cell mediated response elicited by BNT162b2 vaccine in 145 healthcare workers (both naïve and positive for previous SARS-CoV-2 infection) were evaluated. In a subset of subjects, effect of SARS-CoV-2 variants on antibody level and cell-mediated response was also investigated. Results Overall 125/127 (98.4%) naïve subjects developed both neutralizing antibodies and specific T-cells after the second dose. Moreover, the antibody and T-cell responses were effective against viral variants since SARS-CoV-2 NT Abs were still detectable in 55/68 (80.9%) and 25/29 (86.2%) naïve subjects when sera were challenged against beta and delta variants, respectively.T-cell response was less affected, with no significant difference in the frequency of responders (p=0.369). Of note, two-dose of vaccine was able to elicited sustained neutralizing antibody activity against all the SARS-CoV-2 tested variants in SARS-CoV-2 experienced subjects. Conclusions BNT162b2 vaccine elicited a sustained humoral and cell-mediated response in immunocompetent subjects after two-dose administration and it seems to be less affected by SARS-CoV-2 variants, with the only exception of beta and delta variants. An increased immunogenicity, also against SARS-CoV-2 variant strains was observed in SARS-CoV-2 experienced subjects. These results suggest that triple exposure to SARS-CoV-2 antigens might be proposed as valuable strategy for vaccination campaign.

Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney transplant recipients (n = 40) and heart transplant recipients (n = 12). Overall, patients were divided into 2 groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1-year follow-up, all LVL patients had levels of HCMV-specific CD4 (and CD8 ) T cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies and enzyme-linked immunosorbent assay-IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 patient groups. In conclusion, while a valid HCMV-specific T-cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T-cell response. Antibody responses did not appear to be associated directly or indirectly with protection.