ABSTRACT
Evidence is scant regarding the long-term humoral and cellular responses triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in cancer patients after repeated booster doses. The possibility of T-cell exhaustion following these booster doses in this population has not yet been fully studied and remains uncertain. In this observational study, we explored the specific humoral and cellular response to S1 antigen in 36 patients with solid malignancies at baseline, and after the second and third doses of the mRNA-1273 vaccine. A dual behavior was observed: 24 (66.7%) patients showed partial specific IFN-γ response after the second dose that was further enhanced after the third dose; and 11 (30.5%) already showed an optimal response after the second dose and experienced a marked fall-off of specific IFN-γ production after the third (4 patients negativization), which might suggest T cell exhaustion due to repetitive priming to the same antigen. One (2.8%) patient had persistently negative responses after all three doses. Seroconversion occurred in all patients after the second dose. We then studied circulating exhausted CD8 + T-cells in 4 patients from each of the two response patterns, those with increase and those with decrease in cellular response after the third booster. The patients with decreased cellular response after the booster had a higher expression of CD57hiPD1hiCD8+ and CD57intPD1hiCD8+ exhausted T cells compared with those with an increased cellular response both in vivo and in vitro. Our preliminary data show that the two-dose SARS-CoV-2 vaccine regimen was beneficial in all cancer patients. An additional booster seems to be beneficial in non-optimal cancer responders to SARS-CoV-2 vaccines, in contrast to maximal responders that might develop exhaustion. Our data should be interpreted with caution given the small sample size and highlight the urgent need to validate our results in other independent and larger cohorts. Altogether, our data support the relevance of immunological functional studies to personalize preventive and treatment decisions in cancer patients.
ABSTRACT
Patients with antibody deficiency disorders, such as common variable immunodeficiency (CVID), or secondary immunodeficiency (SIDs) to B-cell lymphoproliferative disorder (B-CLPD), are two vulnerable groups of developing severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). Data on adaptive immune responses against SARS-CoV-2 is well described in healthy donors, but still limited in patients with antibody deficiency of different cause. Herein, we analyzed Spike-specific IFN-γ and anti-Spike IgG antibody responses at 3 and 6 months after exposure to SARS-CoV-2 derived from vaccination and infection in two cohorts of immunodeficient patients (CVID vs. SID) compared to healthy controls (HC). Baseline cellular responses before vaccine administration were measured in 10 CVID patients. Adequate specific cellular responses was observed in 18 out of 20 (90%) CVID patients, in 14 out of 20 (70%) out of 20 SID patients and in 74 out of 81 (96%) HC. Specific IFN-γ response was significantly higher in HC respect to CVID (1,908.5 mUI/ml versus 1,694.1 mUI/ml; p = 0.005). Pre-vaccine anti-SARS-CoV-2 cellular responses were detectable in 4 out of 10 CVID patients, who had COVID-19 prior to vaccination, noticing an increase in cellular responses after vaccination (p < 0.001). Whereas all SID and HC mounted a specific humoral immune response, only 80% of CVID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC (p = 0.040), without significant differences between CVID and HC (p = 0.123) and between CVID and SID (p = 0.683). High proportions of CVID and SID patients showed adequate specific cellular responses to S1 neoantigen, with divergence between cellular and humoral immune responses in CVID and SID patients. Our data might support the relevance of these immunological studies to determine the correlate of protection to severe disease and for deciding the need of additional boosters. Follow-up studies are required to evaluate the duration and variability of the immune response to COVID-19 vaccination or infection.