Specific Antibody and the T-Cell Response Elicited by BNT162b2 Boosting After Two ChAdOx1 nCoV-19 in Common Variable Immunodeficiency

Abstract

Common variable immunodeficiency (CVID) patients have markedly decreased immune response to vaccinations. In this study we evaluated humoral and T cell-mediated responses against severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) with additional flow cytometric changes in CVID patients receiving booster vaccination with BNT162b2 after two ChAdOx1 nCoV-19. The BNT162b2 vaccine raised the anti-spike protein S immunoglobulin G over the cut-off value from 70% to 83% in CVID, anti-neutralizing antibody had been raised over a cut-off value from 70% to 80% but levels after boosting were significantly less in both tests than in healthy controls (*p=0.02; **p=0.009 respectively). Anti-SARS-CoV-2 immunoglobulin A became less positive in CVID after boosting, but the difference was not significant. The cumulative interferon-γ positive T cell response by ELISpot was over the cut-off value in 53% of the tested individuals and raised to 83% after boosting. This and flow cytometric control of cumulative CD4+ and CD8+ virus-specific T cell absolute counts in CVID were also statistically not different from healthy individuals after boosting. Additional flow cytometric measures for CD45+ lymphocytes, CD3+, and CD19+ cells have not shown significant differences from controls except for lower CD4+T cell counts at both time points (**p=0.003; **p=0.002), in parallel CD4+ virus-specific T-cell ratio was significantly lower in CVID patients at the first time point (*p: 0.03). After boosting, in more than 33% of both CVID patients and also in their healthy controls we detected a decrease in absolute CD45+, CD3+, CD3+CD4+, and CD3+CD8+, CD19+, and CD16+56+ cell counts. CD16+CD56+ cell counts were significantly lower compared to controls before and after boosting (*p=0.02, *p=0.02). CVID patients receiving immunosuppressive therapy throughout the previous year or autologous stem cell transplantation two years before vaccination had worse responses in anti-spike, anti-neutralizing antibody, CD3+CD4+T, CD19+ B, and natural killer cell counts than the whole CVID group. Vaccinations had few side effects. Based on these data, CVID patients receiving booster vaccination with BNT162b2 after two ChadOx1 can effectively elevate the levels of protection against COVID-19 infection, but the duration of the immune response together with COVID-19 morbidity data needs further investigation among these patients.

Impaired B Cell Recall Memory and Reduced Antibody Avidity but Robust T Cell Response in CVID Patients After COVID-19 Vaccination

“…Previous data suggested a correlation between reduced specific humoral immune response and impaired specific T cellular immunity in CVID patients [ 17 , 27 ]. Our findings contrast this observation, with all CVID seroresponder and 5/6 non-seroresponder showing a robust polyfunctional CD4 + T cell immune response thus complementing previous reports of robust specific SARS-CoV-2 T cell responses in CVID patients with mild [ 28 ] and severe SARS-CoV-2 infections [ 29 ] as well as to COVID-19 vaccination [ 8 – 10 ] and other vaccines, such as influenza [ 30 , 31 ]. A limitation of our study is the relatively long period of collecting samples in CVID patients and HC.…”

“…Findings on humoral immune response after COVID-19 vaccination are variable with frequencies of seroresponding CVID patients ranging from 20 to 95% [ 6 – 12 ]. A positive T cellular immune response was reported in 46–83% of CVID patients [ 8 , 10 – 15 ]. Reasons for the observed variability might include differences in methodology and different vaccination regimens as well as clinical, immunological, and genetic heterogeneity of CVID patients.…”

“…Detailed characterizations regarding B cell memory formation are limited and suggest an atypical memory formation [ 17 ]. Without affecting seroconversion rates, booster vaccination in CVID patients was shown to further increase antibody levels in some seroresponder [ 9 , 18 ], while effects of boosting on specific T cell immunity is variable [ 9 , 10 ].…”

Safety of mRNA COVID-19 Vaccines in Patients with Inborn Errors of Immunity: an Italian Multicentric Study

“…This is also highlighted by a recent Hungarian study, testing specific antibody and the T cell response elicited by BNT162b2 boosting after two ChAdOx1 shots in a cohort of CVID patients, compared with healthy control subjects. The authors also reported the AE profile, showing that CVID patients who had a worse immune response to vaccinations might have a slightly reduced rate of systemic side effects [31].…”

Immunizing the imperfect immune system

“…Additional longitudinal studies of vaccine efficacy in IEI are currently underway (NCT04852276) and it is hoped to provide further guidance to clinicians and patients regarding best methods to prevent COVID-19 in this population. 42,45,48,51,52,57,59,73…”