Serum neutralizing capacity and T-cell response against the omicron BA.1 variant in seropositive children and their parents one year after SARS-CoV-2 infection

Abstract

Introduction: Durability of immune protection against reinfection with SARS-CoV-2 remains enigmatic, especially in the pediatric population and in the context of immune-evading variants of concern. Obviously, this knowledge is required for measures to contain the spread of infection and in selecting rational preventive measures.

Methods: Here, we investigated the serum neutralization capacity of 36 seropositive adults and 34 children approximately one year after infection with the ancestral Wuhan strain of SARS-CoV-2 by using a pseudovirus neutralization assay.

Results: We found that 88.9% of seropositive adult (32/36) and 94.1% of seropositive children (32/34) convalescents retained the neutralizing activity against the SARS-CoV-2 Wuhan strain (WT). Although, the neutralization effect against Omicron BA.1 (B.1.1.529.1) was significantly lower, 70.6% (24/34) of children and 41.7% (15/36) of adults possessed BA.1 cross-neutralizing antibodies. The spike 1 (S1)-specific T cell recall capacity using an activation-induced marker assay was analyzed in 18 adults and 16 children. All participants had detectable S1-specific CD4 T cells against WT, and 72.2% (13/18) adults and 81,3% (13/16) children had detectable S1 WT-specific CD8 T cells. CD4 cross-reactivity against BA.1 was demonstrated in all investigated adults (18/18), and 66.7% (12/18) adult participants had also detectable specific CD8 BA.1 T cells while we detected BA.1 S1 reactive CD4 and CD8 T cells in 81.3% (13/16) children.

Discussion: Together, our findings demonstrate that infection with the ancestral strain of SARS-CoV-2 in children as well as in adults induces robust serological as well as T cell memory responses that persist over at least 12 months. This suggests persistent immunological memory and partial cross-reactivity against Omicron BA.1.

Keywords: SARS-CoV-2; T cells; children; neutralizing antibody; omicron variant; variant of concern.

Figure 1

Comparison of serum neutralization capacity and S1-specific T cells against Wuhan strain (WT) and omikron BA.1 (B.1.1.529.1) in adults and children circa 12 months after infection with ancestral SARS-CoV-2 strain. (A) Serum neutralization capacity in convalescent adults (triangles) and children (circles) was measured with a pseudovirus neutralization assay against WT (empty symbols) and BA.1 (B.1.1.529.1; filled symbols). The results are presented as serum dilution resulting in 50% pseudovirus neutralization (PVNT50) on cells, calculated by nonlinear regression [(inhibitor) vs. normalized response—variable slope]. The upper and lower cut-off values of this assay were set at PVNT50 > 81.920 and <20 (dotted line), respectively. Median values are plotted with a line. (B,C) In all available stored peripheral blood mononuclear cells (PBMC) samples S1-specific CD4 and CD8 T cells were measured with activation-induced marker (AIM) assay using two sets of stimulating peptides (see methods). The same symbols as in the serum neutralization assay are applied; the results from participants with missing neutralization against BA.1 are marked with blue color. The results are presented as percentage of activated T cells (expressing CD137 and CD69) out of the particular T cell subset. The cut-off for positivity (dotted line) was set at 0.07% and 0.04% for CD4 and CD8 T cells, respectively; background values after stimulation with DMSO are subtracted. Numbers of positive samples out of all measured samples are displayed above the particular analysis. The Wilcoxon matched-pairs signed rank test was used for paired samples; Mann-Whitney test was used for the non-paired ones. Statistical significance was defined as ***p ≤ 0.001; only statistically significant differences are marked.