SARS-CoV-2 vaccines elicit differential Fc effector functions

Figures

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  Figure 1. Dosing and sampling strategy of individuals vaccinated with BNT162b2, Ad26.COV2.S and ChAdOx1 nCoV-19 (A) BNT162b2 participants (orange, n = 13) were vaccinated using a two-dose strategy with first dose at day 0, second dose after 42 days, and boosted with an additional third dose after 5.5 months. Participants who received the BNT162b2 vaccine were sampled after receiving a full primary vaccination i.e., 2 doses, and 1 month post boost (PB). The post full primary vaccination blood samples were taken 2 months after the initial dose, which translated to a month following their second dose. Although the primary vaccination sampling period was a month less than the other vaccine groups, these samples were regarded as peak immunogenicity because they were taken following the full 2 dose primary vaccination strategy recommended for BNT162b2. (B) Ad26.CoV2.S (blue, n = 13) was administered as one primary dose received at month 0 and individuals were subsequently boosted 7.5 months after the initial dose. The participants were sampled 2 months after the first dose and 1 month after the second dose. (C) ChAdOx1 nCoV-19 trial participants (purple, n = 23) were vaccinated with a two-dose…

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  Figure 2. Binding and neutralizing antibody responses across vaccine modalities Binding antibody titers against ancestral D614G tested by ELISA (A) approximately 2 months following the first vaccine dose and (B) longitudinally over time (1 month post boost (PB) and 6 months 2nd dose follow-up (2nd dose FU). Neutralization of ancestral (D614G) pseudovirus (C) approximately 2 months following the first dose and (D) over time (1 month post boost (PB) and 6 months 2nd dose follow-up (2nd dose FU). BNT162b2 vaccinees are shown in orange, Ad26.CoV2.S in blue and ChAdOx1 nCoV-19 in purple. Ad26.CoV2.S vaccinees with nucleocapsid ELISA confirmed breakthrough infections 2 months before they acquired a booster dose, were excluded from further analysis in Figures 2B and 2D, to prevent the influence of hybrid immunity. Horizontal lines indicate geometric mean binding or neutralization titers (GMT), with change in vaccine elicited neutralization before and after boost represented as a fold change between post boost and pre-boost GMT. Palivizumab (black), the negative control is included, with a dotted line on the y axis indicating the positivity cut-off for binding. The detection limit of ID50 of 20,…

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  Figure 3. BNT162b vaccination triggers Fc effector responses with enhanced magnitude compared to Ad26.CoV2.S and ChAdOx1 nCoV-19 Fc effector functions against ancestral D614G were measured approximately 2 months following vaccination with BNT162b2 (orange), Ad26.CoV2.S (blue) or ChAdOx1 nCoV-19 (purple). (A) Antibody-mediated cellular cytotoxicity (ADCC) potential against the ancestral D614G variant is represented as relative light units (RLUs) triggered through activation of FcγRIIIa receptor on CD16 Jurkat cells, (B) Antibody dependent cellular phagocytosis (ADCP) is shown as the percentage of THP-1 cells that take up spike-coated beads multiplied by their geometric mean fluorescence intensity (MFI) (C) Antibody dependent complement deposition (ADCD) is illustrated as the Median Fluorescence Intensity (MFI) of the C3 protein deposited on spike coated beads. The horizontal lines represent the medians. (D) ADCC, (E) ADCP and (F) ADCD against ancestral D614G were also measured over time, 1 month post boost (PB) and/or 6 months post first dose (2nd dose follow-up FU). Median ADCC, ADCP and ADCD per vaccine, are shown below the graphs with fold changes relative to the first dose. Negative…

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  Figure 4. Vaccines elicit unique patterns of neutralization and Fc effector cross-reactivity against VOCs (A) Spider plots demonstrating vaccine elicited neutralization of D614G, Beta, Delta, BA.1 pseudovirus shown as a geometric mean titers (GMT) following 2 doses of BNT162b2 (orange), a single dose of Ad26.CoV2.S (blue), and two doses of ChAdOx1 nCoV-19 (purple). (B) Neutralization cross-reactivity scores calculated as a cumulative area under the curve or spiderplot (AUC) are shown. (C) Antibody-mediated cellular cytotoxicity (ADCC) potential against the ancestral D614G, Beta, Delta, and BA.1 variants is represented as a geometric mean (GM) relative light units (RLUs), (D) overall ADCC cross-reactivity as AUC generated from C. (E) Antibody dependent cellular phagocytosis (ADCP) represented as a GM ADCP score and (F) overall ADCP cross-reactivity as AUC generated from E. (G) Antibody dependent complement deposition (ADCD) against D614G, Beta, Delta, and BA.1 is illustrated as GMT of the median Fluorescence Intensity (MFI) of the C3 protein deposited on beads and (H) overall ADCD cross-reactivity as AUC generated from G. Fold changes in cross-reactivity are indicated relative to BNT162b2…

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  Figure 5. Vaccine platforms induce differential coordination of binding, neutralization and Fc effector functions (A–C) Edge bundling plots showing Spearman’s correlations between neutralization, binding and Fc effector functions against D614G, approximately 2 months post primary vaccination schedule with two doses of BNT162b2 (A), one dose of Ad26.CoV2.S (B) and two doses of ChAdOx1 nCoV-19 (C). Red lines represent positive correlations while blue lines show negative correlations with intensity of the color indicating the strength of the correlation. Statistically significant correlations are indicated with asterisks, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 and a comprehensive Table S2 has been included to indicate p-values and confidence intervals for all the correlations in support of Figure 5.