Binding and neutralizing antibody responses to SARS-CoV-2 in very young children exceed those in adults

Karron, Ruth A.; Quesada, Maria Garcia; Schappell, Elizabeth; Schmidt, Stephen D.; Knoll, Maria Deloria; Hetrich, Marissa K.; Veguilla, Vic; Doria‐Rose, Nicole A.; Dawood, Fatimah S.

doi:10.1172/jci.insight.157963

Cited by 19 publications

(11 citation statements)

References 20 publications

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“…Consistently, a very recent study reported that young children aged 0-4 years generally develop significantly higher titers of neutralizing antibody than adults. This study also documented a stepwise downward progression in binding-to-neutralizing (B/ N) antibody titer ratio with age: children aged 0-4 years had the highest ratio of B/N antibody, children aged 5-17 years had an intermediate level, and adults had the lowest (21). So far, the exact mechanisms underlying the different SARS-CoV-2 antibody responses based on age remain unclear.…”

Section: Discussionmentioning

confidence: 62%

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial

Xia

Duan²,

Zhang³

et al. 2022

Front. Immunol.

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Safe and effective vaccines against SARS-CoV-2 for children are urgently needed. Here we aimed to assess the safety and immunogenicity of an inactivated COVID-19 vaccine candidate, WIBP-CorV, in participants aged 3-17 years. A randomized, double-blind, placebo-controlled, phase 1/2 clinical trial was conducted in Henan Province, China, in healthy children aged 3-17 years. 240 participants in phase 1 trial and 576 participants in phase 2 trial were randomly assigned to vaccine or control with an age de-escalation in three cohorts (3-5, 6-12 and 13-17 years) and dose-escalation in three groups (2.5, 5.0 and 10.0μg/dose), and received 3 intramuscular injections at day 0, 28, and 56. WIBP-CorV showed a promising safety profile with approximately 17% adverse reactions within 30 days after injection and no grade 3 or worse adverse events. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting. The geometric mean titers of neutralizing antibody ranged from 102.2 to 1065.5 in vaccinated participants at 28 days after the third vaccination, and maintained at a range of 14.3 to 218.2 at day 180 after the third vaccination. WIBP-CorV elicited significantly higher titers of neutralizing antibody in the cohort aged 3-5 years than the other two cohorts. There were no detectable antibody responses in all alum-only groups. Taken together, our data demonstrate that WIBP-CorV is safe and well tolerated at all tested doses in participants aged 3-17 years, and elicited robust humoral responses against SARS-CoV-2 lasted for at least 6 months after the third vaccination. This study is ongoing and is registered with www.chictr.org.cn, ChiCTR2000031809.

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Section: Discussionmentioning

confidence: 62%

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial

Xia

Duan²,

Zhang³

et al. 2022

Front. Immunol.

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“…Concerning the high titers of anti-S among children in our study, similar results were noted by Garrido et al, who reported higher anti-RBD and neutralizing antibodies in children than in adults, up to 4 months post-COVID-19 infection [ 34 ]. In addition to cross-reactivity with other coronaviruses, Karron et al, explained the higher SARS-CoV-2 seropositivity among children by their exaggerated tenfold higher RBD antibody titers than adults, while adults had a higher neutralizing ability than children [ 35 ]. Children were reported to have more durable, yet immature RBD-specific antibody responses [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

A pre-vaccine exploratory survey of SARS-CoV-2 humoral immunity among Egyptian general population

et al. 2022

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Background Population-based studies on COVID-19 have important implications for modeling the pandemic and determining vaccination policies. Limited data are available from such surveys in Egypt. Methods This cross-sectional was conducted throughout the period between January and June 2021, which coincided with the second and third waves of the COVID-19 pandemic in Egypt. At that time, vaccines against COVID-19 were not available to the general population. The study was carried out in eight Egyptian governorates and included 2360 participants, who were recruited through a multistage stratified cluster sample technique, based on gender, age, and district followed by a random sample within each district. Socio-demographic data were recorded and serum samples were collected and tested for SARS-Co-V2 spike (S) antibodies. Results The overall adjusted prevalence of anti-S was 46.3% (95% CI 44.2–48.3%), with significant differences between governorates. Factors associated with anti-S seropositivity were: being female (p = 0.001), living in a rural area (p = 0.008), and reporting a history of COVID-19 infection (p = 0.001). Higher medians of anti-S titers were significantly associated with: extremes of age (p < 0.001), living in urban areas, having primary education (p = 0.009), and reporting a history of COVID-19 infection, especially if based on chest CT or PCR (p < 0.001). Conclusions High seroprevalence rates indicate increased COVID-19 infection and immune response among a considerable percentage of the community. Age, gender, residence, educational level, and previous PCR-confirmed COVID-19 infections were all determinants of the immune response.

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“…The observation that IgG titers against nucleocapsid and SH-H were the same in infants and adults in this study suggests that the stronger responses in infants to other domains cannot simply be explained by higher overall B lymphocyte levels reported in infants versus adults (O’Gorman et al, 1998). Previous studies have detected lower (Hachim et al, 2022), higher (Karron et al, 2022; Yang et al, 2021), or equivalent (Goenka et al, 2021; Weisberg et al, 2021) levels of antibody binding to Spike or its subdomains in pediatric cohorts compared to adults. One possible reason for this variation is the inclusion of children who span a wide age range in prior studies, whereas this study specifically focused on infants (under 19 months of age), with samples collected within a single cohort study (Begnel et al, 2023).…”

Section: Discussionmentioning

confidence: 92%

“…While prior studies have assessed neutralization capacity in cohorts that include older children (Dowell et al, 2022; Karron et al, 2022; Weisberg et al, 2021; Yang et al, 2021), few studies have assessed SARS-CoV-2 antibody function (Goenka et al, 2021) in infants early in life or directly compared antibody responses in infants and adults. Though antibody neutralization of SARS-CoV-2 remains a key component of protective and therapeutic immunity, there is increasing evidence for the importance of non-neutralizing antibody effector functions, such as Fc receptor-mediated antibody-dependent cellular cytotoxicity (ADCC) in protection against SARS-CoV-2 (Beaudoin-Bussieres et al, 2022; Di Vito et al, 2022; Pierce et al, 2020; Rostad et al, 2022; Tauzin et al, 2021; Yu et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers

Stoddard

Sung

Yaffe

et al. 2023

Preprint

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Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants, and direct comparisons between infants and adults are limited. We characterized antibody binding and functionality in convalescent plasma from postpartum women and their infants infected with SARS-CoV-2 from a vaccine-naive prospective cohort in Nairobi, Kenya. Antibody titers against SARS-CoV-2 Spike, receptor binding domain and N-terminal domain, and Spike-expressing cell-surface staining levels were significantly higher in infants than in mothers. Plasma antibodies from mothers and infants bound to similar regions of the Spike S2 subunit, including the fusion peptide (FP) and stem helix-heptad repeat 2. However, infants displayed higher antibody levels and more consistent antibody escape pathways in the FP region compared to mothers. Finally, infants had significantly higher levels of antibody-dependent cellular cytotoxicity (ADCC), though, surprisingly, neutralization titers between infants and mothers were similar. These results suggest infants develop distinct SARS-CoV-2 binding and functional antibody repertoires and reveal age-related differences in humoral immunity to SARS-CoV-2 infection that could be relevant to protection and COVID-19 disease outcomes.

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Binding and neutralizing antibody responses to SARS-CoV-2 in very young children exceed those in adults

Cited by 19 publications

References 20 publications

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial

A pre-vaccine exploratory survey of SARS-CoV-2 humoral immunity among Egyptian general population

Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers

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