Infection and Vaccine Induced Spike Antibody Responses Against SARS-CoV-2 Variants of Concern in COVID-19-Naïve Children and Adults

Figures

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  Fig. 1. Persistence of sera Spike antibodies against natural variants in children and adults. a Schematic showing timeline of different waves of infections in Australia. Convalescent patient sera from individuals naturally infected with Early Clade, Delta, or Omicron Spike or vaccinated individuals were examined for SARS-CoV-2 antibodies in a total of 47 children and 40 adults. In each cohort, the dots indicate the beginning and end of the sample collection timeframe. b IgG, IgM, and IgA responses against Spike over time in Early Clade–infected children (ages 0–18 years old, peach) and adults (>18 years old, gray) shown since viral exposure. c COVID-19 severity caused by the Early Clade SARS-CoV-2 was mostly mild or asymptomatic in children, whereas “close contact” inter-related adults presented more often with a moderate disease which was associated with higher Spike IgG levels. d Schematic indicating primary mutations in VOCs within the Spike protein. e Peak IgG responses generated against Early clade, Delta, BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1 Spike VOCs in naturally infected individuals. f Peak IgG responses generated against Early Clade, Delta, BA.1, BA.2, BA.5, BQ.1.1,…

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  Fig. 2. Spike IgG immunoreactivity against VOCs in naturally infected and vaccinated children and adults. a Schematic showing mutations within VOCs along SARS-CoV-2 Spike protein. b WHO International NIBSC SARS-CoV-2 standard (20/136) tested against VOCs and titer of IgG against VOCs. c WHO International NIBSC SARS-CoV-2 standard (21/234) tested against VOCs and cross-reactive binding compared to Early Clade Spike (percentage). Evaluation of Spike VOCs cross-reactive binding in comparison to Early Clade Spike in sera samples from d naturally Early Clade–infected children (n=14) and adults (n=5), e naturally Delta-infected children (n=9) and adults (n=9), f naturally Omicron-infected children (n=6) and adults (n=3), and g vaccinated children (n=8), adults who received BNT162b2 vaccine (n=8), and adults who received ChAdOx1 vaccine (n=8). Summarized comparison of immunoreactivity across VOCs in different cohorts of h children and i adults. All points shown were collected at the peak of the immune response (Table 1) and were seropositive against a control cohort and calculated positive threshold. The dotted line shows the reference binding on Early Clade Spike. p values were determined by…

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  Fig. 3. Additive effects of mutations within SARS-CoV-2 Spike RBD. a Schematic showing mutations in different VOCs at specific positions within the SARS-CoV-2 Spike protein. b WHO International NIBSC SARS-CoV-2 standard tested on variants Delta, Kappa, and Epsilon, titer of Ab binding to variants (left) and cross-reactive binding compared to Early Clade Spike (percentage) (right). Proportion of Spike VOC cross-reactive binding compared to Early Clade Spike in sera samples from c Early Clade–infected individuals, d Delta-infected individuals, e Omicron-infected individuals, and f vaccinated individuals. g Summarized comparison of immunoreactivity toward Kappa and Delta Spike variants across different cohorts. h Mutations within SARS-CoV-2 Spike variants within the RBD. i WHO International NIBSC SARS-CoV-2 standard tested on Eta and Early Clade Spike variants, titers of Ab binding to variants (left) and cross-reactive binding compared to Early Clade Spike (right). Cross-reactive binding compared to Early Clade Spike VOC against Eta, Beta, Gamma, and Alpha Spike variants in j Early Clade–infected individuals, k Delta-infected individuals, l Omicron-infected individuals, and m vaccinated…

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  Fig. 4. Epistatic effect of mutations within the Spike RBD. a Schematic of mutation within the RBD for AM1 Spike, D.2 Spike, AM2 Spike, and Omicron subvariants. b Cross-reactive binding against AM1, D.2, AM2, BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1 Spikes in sera from Early Clade–infected individuals, c Delta-infected individuals, d Omicron-infected individuals, and e vaccinated individuals. f Summarized comparison of cross-reactive binding toward AM1 Spike, D.2 Spike, and AM2 Spike across different cohorts. All points shown were collected at the peak of the immune response (Table 1) and were seropositive against a control cohort and calculated positive threshold. The dotted line shows the reference binding on Early Clade Spike. p values were determined by comparing VOC Spikes vs Early Clade Spike. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. ∆MFI, delta median fluorescence intensity; Ab, antibody; VOCs, variants of concern