Systemic IL-15, IFN-γ, and IP-10/CXCL10 signature associated with effective immune response to SARS-CoV-2 in BNT162b2 mRNA vaccine recipients

Abstract

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

Long-term predictions of humoral immunity after two doses of BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex

“…[22], which begin on day ∼ 50 past dose one, an interval-censored data point was added to day 1 to guide the initial condition fit, where the allowable initial range of the fit is bounded within all the initial day 1 IgG values used in this work. Final clinical data points for IL-15 and IL-6 were gathered immediately after dose two where these quantities have peaked, such that the subsequent decay was not characterized [19]. To ensure the eventual decrease in these cytokines as a function of time in our modelled prediction, we added an interval-censored data point on day 200, which ensures the fit on this day is between 0 and the minimal value determined on day 1 for each respective concentration.…”

“…1a. Similarly we do the same for the BNT162b2 two-dose result, where we average the individual IgG fitted parameters from Tables S3 and S4 from Stankov et al [18], Bergamaschi et al [19], Camara et al [20], Wang et al [22], and Suthar et al [23]. The result is shown as the red points with corresponding average fit in Fig.…”

“…In comparison, two doses of mRNA-1273 and BNT162b2 have shown seroconversion in the short term that surpasses that of recovered patients: one month post second dose, antibody stimulation (IgG and IgM) is reported to be higher while neutralizing antibodies are shown to be similar to recovered patients for fully vaccinated individuals [12, 13, 14]. In vaccinated individuals, studies of antibodies responses are predominantly short- (less than 60 days) and mediumterm (less than 120 days) studies [11, 15, 16, 17, 18, 19, 20, 21, 22], with one recent study examining antibody response out to day 210 [23]. With the continued emergence of new variants of concern, there is now a key gap in the understanding of the long-term (beyond 120 days) robustness of the two-dose LNP-formulated mRNA vaccines adopted by health authorities.…”

“…To address this gap, we established an ODE-based mechanistic model that describes the humoral immune response of mRNA vaccines to predict long term immunity. We fit our model to reported antibody and cytokine levels to clinical trial data using two standard doses of mRNA-1273 (100 μ g) or BNT162b2 (30 μ g) [17, 18, 19, 20, 21, 22], as well as separately to two low doses of mRNA-1273 (25 μ g) [24]. Model results show significant decay in antibody a few months after dose-two inoculation, with the decay rate depending on the vaccine type, dose size, and age of the vaccine recipient.…”

Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma

“…An in-house ELISA measuring IgG was used to determine antibodies against the complete Spike protein, Spike-Receptor binding domain (Spike-RBD), complete Nucleocapsid protein (N), and Nucleocapsid-RNA binding domain (N-RBD), as previously described. The in-house assay measuring Spike shows excellent correlation with the ROCHE assay but has a larger range of detection and is more sensitive [ 22 , 23 ]. The cut-off values were determined using 17–23 healthy human plasma samples collected between 2015 and 2018 and tested against the different antigens, and the mean and standard deviation were calculated as previously described [ 22 ].…”