Systemic IL-15, IFN-g, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients Graphical abstract Highlights d BNT162b2 mRNA vaccine induces a cytokine signature featuring IL-15, IFN-g, and CXCL10 d mRNA-vaccine-induced IFN-g and IL-15 correlate with spike antibody response d Strong cytokine signature upon a single vaccination of convalescent persons d Stronger cytokine induction upon booster vaccination in naive persons
Background
Coronavirus SARS-CoV-2, the causative agent of COVID-19, has caused a still evolving global pandemic. Given the worldwide vaccination campaign, the understanding of the vaccine-induced versus COVID-19-induced immunity will contribute to adjusting vaccine dosing strategies and speeding-up vaccination efforts.
Methods
Anti-spike-RBD IgGs and neutralizing antibodies (NAbs) titers were measured in BNT162b2 mRNA vaccinated participants (n = 250); we also investigated humoral and cellular immune responses in vaccinated individuals (n = 21) of this cohort 5 months post-vaccination and assayed NAbs levels in COVID-19 hospitalized patients (n = 60) with moderate or severe disease, as well as in COVID-19 recovered patients (n = 34).
Results
We found that one (boosting) dose of the BNT162b2 vaccine triggers robust immune (i.e., anti-spike-RBD IgGs and NAbs) responses in COVID-19 convalescent healthy recipients, while naïve recipients require both priming and boosting shots to acquire high antibody titers. Severe COVID-19 triggers an earlier and more intense (versus moderate disease) immune response in hospitalized patients; in all cases, however, antibody titers remain at high levels in COVID-19 recovered patients. Although virus infection promotes an earlier and more intense, versus priming vaccination, immune response, boosting vaccination induces antibody titers significantly higher and likely more durable versus COVID-19. In support, high anti-spike-RBD IgGs/NAbs titers along with spike (vaccine encoded antigen) specific T cell clones were found in the serum and peripheral blood mononuclear cells, respectively, of vaccinated individuals 5 months post-vaccination.
Conclusions
These findings support vaccination efficacy, also suggesting that vaccination likely offers more protection than natural infection.
Graphical abstract
The urgency of the COVID-19 pandemic has led to accelerated vaccine development within less than a year. Immunocompromised patients with hematological malignancies are more susceptible to COVID-19 and at higher risk of severe complications and worse outcomes compared with general population. In this context, we evaluated the humoral response by determining the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with Waldenstrom Macroglobulinemia (WM) after vaccination with the BNT162b2 or AZD1222 vaccine. An FDA-approved, ELISA-based methodology was implemented to evaluate NAbs on the day of the first vaccine shot, as well as on day 22 and 50 afterwards. 106 patients with WM (43% males, median age 73 years) and 212 healthy controls (46% males, median age 66 years) who were vaccinated during the same period, at the same center were enrolled in the study (which is registered at www.clinicaltrials.gov as NCT04743388). Our data indicate that vaccination with either 2 doses of the BNT162b2 or 1 dose of the AZD1222 vaccine leads to lower production of NAbs against SARS-CoV-2 in patients with WM compared with controls both on day 22 and on day 50 (P<0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with either Rituximab or Bruton's Tyrosine Kinase inhibitors was proven as an independent prognostic factor for suboptimal antibody response following vaccination. In conclusion, patients with WM have low humoral response following COVID-19 vaccination, which underlines the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.
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