Younger Children Develop Higher Effector Antibody Responses to SARS-CoV-2 Infection

Tomasi, Lisa; Thiriard, Anaïs; Heyndríckx, Leo; Georges, Daphnée; Wijngaert, Sigi Van den; Olislagers, Véronique; Sharma, Shilpee; Matagne, André; Ackerman, Margaret E.; Ariën, Kevin K.; Goetghebuer, Tessa; Marchant, Arnaud

doi:10.1093/ofid/ofac554

Cited by 9 publications

(3 citation statements)

References 32 publications

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“…Numerous cellular and humoral deficiencies define the immature immune system, however, altered antibody class switching ( 220 , 221 ) and IgG glycosylation ( 372 , 373 ) confer young children unique Fc effector profiles. Rational vaccine design which exploits the elevated Fc capacity ( 37 , 324 , 374 , 375 ) of childhood humoral immunity may promote optimised protection.…”

Section: Dysregulated Fc Effector Functions Characterise Vulnerable P...mentioning

confidence: 99%

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

et al. 2023

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Vaccine efficacy determined within the controlled environment of a clinical trial is usually substantially greater than real-world vaccine effectiveness. Typically, this results from reduced protection of immunologically vulnerable populations, such as children, elderly individuals and people with chronic comorbidities. Consequently, these high-risk groups are frequently recommended tailored immunisation schedules to boost responses. In addition, diverse groups of healthy adults may also be variably protected by the same vaccine regimen. Current population-based vaccination strategies that consider basic clinical parameters offer a glimpse into what may be achievable if more nuanced aspects of the immune response are considered in vaccine design. To date, vaccine development has been largely empirical. However, next-generation approaches require more rational strategies. We foresee a generation of precision vaccines that consider the mechanistic basis of vaccine response variations associated with both immunogenetic and baseline health differences. Recent efforts have highlighted the importance of balanced and diverse extra-neutralising antibody functions for vaccine-induced protection. However, in immunologically vulnerable populations, significant modulation of polyfunctional antibody responses that mediate both neutralisation and effector functions has been observed. Here, we review the current understanding of key genetic and inflammatory modulators of antibody polyfunctionality that affect vaccination outcomes and consider how this knowledge may be harnessed to tailor vaccine design for improved public health.

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Section: Dysregulated Fc Effector Functions Characterise Vulnerable P...mentioning

confidence: 99%

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

et al. 2023

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“…Although the underlying physiologic mechanisms remain incompletely understood, cumulative evidence suggests distinct SARS-CoV-2 antibody responses in children and adults (17, 18), and the early robust innate immune response and trained immunity may play an important role (19). Several studies also found that children tended to have higher levels of antibody responses after SARS-CoV-2 infection compared to adults (20,21). In terms of seroconversion rate at 28 days after full course of vaccination, it was as high as 99.86% for all participants in this trial, which was in similar level to the seroconversion rate in all age populations in our previous clinical trials (12)(13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity, safety and consistency of seven lots of an inactivated COVID-19 vaccine in healthy children and adolescents: a randomized, double-blind, controlled, phase IV clinical trial

Hu,

Liu,

et al. 2024

Front. Immunol.

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BackgroundCoronaVac has been authorized worldwide for preventing coronavirus disease 2019. Information on the safety, immunogenicity and consistency of different lots and workshops of CoronaVac is presented here.MethodsIn this randomized, double-blind, phase IV clinical trial in healthy children and adolescents aged 3-17 years, we aimed to assess the lot-to-lot and workshop-to-workshop consistency, as well as immunogenicity and safety of seven lots of commercial-scale CoronaVac from three workshops. Eligible participants were enrolled into three age cohorts (3-5, 6-11 and 12-17 years). Within each cohort, participants were randomly assigned to seven groups to receive two doses of CoronaVac, with four weeks apart. Serum samples were collected before the first dose and 28 days after the second dose for neutralizing antibody testing. The primary objective was to evaluate the consistency of immune response among different lots within workshop 2 or 3, as well as among different workshops. The primary endpoint was geometric mean titer (GMT) of neutralizing antibody at 28 days after full-course vaccination.ResultsBetween July 27th and November 19th, 2021, a total of 2,520 eligible participants were enrolled. Results showed that 95% confidence intervals (CIs) of GMT ratios for all comparative groups among different lots or workshops were within the equivalence criteria of [0.67, 1.5]. The GMT and seroconversion rate for all participants were 126.42 (95%CI: 121.82, 131.19) and 99.86% (95%CI: 99.59%, 99.97%) at 28 days after two-dose vaccination. The incidences of adverse reactions were similar among seven lots, and most adverse reactions were mild in Grade 1, with no serious adverse event.ConclusionCoronaVac is well-tolerated and can elicit a good immune response among children and adolescents. Lot-to-lot consistency results indicate stable manufacturing of commercial-scale CoronaVac.

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“…10,11 Distinct antibody immune response dynamics are suggested in children compared to adults, but some results are conflicting between studies and many questions remain. 10,12,13 Cell-mediated immunity is more complex to study and less has been published on the role of T cells in the acute and convalescent phases of infection in children, despite its importance in antiviral immunity and vaccine development. [14][15][16][17] The goal of this study was to describe and compare the long-term adaptive immunity following SARS-CoV-2 infection in children and adults.…”

Section: Introductionmentioning

confidence: 99%

Differential Adaptive Immune Responses Following SARS-CoV-2 Infection in Children Compared to Adults

Nantel,

Arnold,

Bhatt

et al. 2024

Preprint

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Background : SARS-CoV-2 infection elicits distinct clinical features in children and adults. Profiling the adaptive immune response following infection in children is essential to better understand and characterize these differences. Methods : Humoral and cell-mediated immune responses from unvaccinated pediatric and adult participants were analyzed following asymptomatic or mild non-Omicron SARS-CoV-2 infection. Levels of IgG and IgA targeting spike (S), receptor-binding domain (RBD), and nucleocapsid (N) proteins of SARS-CoV-2 were measured, while neutralizing antibody (nAb) titers were assessed against three viral strains (Wuhan, Omicron BA.1 and BA.4/BA.5). Specific T-cell memory responses were investigated by quantifying interferon-gamma secreting cells after stimulation with ancestral and variant strains of SARS-CoV-2, and seasonal human coronaviruses HCoV-OC43 and HCoV-HKU1. Results : The study comprised 28 children (3 to 17 [median=10] years old) and 28 adults (19 to 62 [median=42]). At a mean time of seven months (+/- 2.8 months) after SARS-CoV-2 infection, children and adults mounted comparable antibody levels against S and RBD, as well as similar neutralization capacity. However, children displayed a weaker cellular memory response to SARS-CoV-2 than adults, with a median of 88 [28-184] spot forming units per million of PBMCs in children compared to 208 [141-340] in adults (***, P < .001). In children, the level of IFN-gamma secreting cells in response to SARS-CoV-2 corresponds to that of seasonal coronaviruses. Conclusion : Long-term memory T-cell responses to SARS-CoV-2 are enhanced in adults compared to children who demonstrate equivalent responses to SARS-CoV-2 and other HCoV.

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Younger Children Develop Higher Effector Antibody Responses to SARS-CoV-2 Infection

Cited by 9 publications

References 32 publications

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

Immunogenicity, safety and consistency of seven lots of an inactivated COVID-19 vaccine in healthy children and adolescents: a randomized, double-blind, controlled, phase IV clinical trial

Differential Adaptive Immune Responses Following SARS-CoV-2 Infection in Children Compared to Adults

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