Robust and durable serological response following pediatric SARS-CoV-2 infection

Renk, Hanna; Dulovic, Alex; Seidel, Alina; Becker, Matthias; Fabricius, Dorit; Zernickel, Maria; Junker, Daniel; Groß, Rüdiger; Müller, Janis A.; Hilger, Alexander; Bode, Sebastian; Fritsch, Linus; Frieh, Pauline; Haddad, Anneke D. M.; Görne, Tessa; Remppis, Jonathan; Ganzemueller, Tina; Dietz, Andrea; Huzly, Daniela; Hengel, Hartmut; Kaier, Klaus; Weber, Susanne; Jacobsen, Eva‐Maria; Kaiser, Philipp; Traenkle, Bjoern; Rothbauer, Ulrich; Stich, Maximilian; Tönshoff, Burkhard; Hoffmann, Georg F.; Müller, Bárbara; Ludwig, Carolin; Jahrsdörfer, Bernd; Schrezenmeier, Hubert; Peter, Andreas; Hörber, Sebastian; Iftner, Thomas; Münch, Jan; Stamminger, Thomas; Groß, Hans‐Jürgen; Wolkewitz, Martin; Engel, Corinna; Liu, Weimin; Rizzi, Marta; Hahn, Beatrice H.; Henneke, Philipp; Franz, Axel R.; Debatin, Klaus‐Michael; Schneiderhan‐Marra, Nicole; Janda, Aleš; Elling, Roland

doi:10.1038/s41467-021-27595-9

Cited by 67 publications

(80 citation statements)

References 34 publications

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“…Having determined that mRNA vaccines produce a significantly higher proportion of RBD and S1 antibodies, we next investigated their ACE2 binding inhibition as these antigens are predominantly responsible for antibody-mediated virus neutralization ( 12 , 13 ). For this, we used a previously published ACE2-RBD competition assay ( 22 , 29 , 30 ), which detects neutralizing antibody activity only and is comparable to classical viral neutralization assays ( 24 , 29 ). As expected, homologous mRNA vaccination resulted in higher ACE2 binding inhibition than homologous vector-based vaccination (median ACE2 binding inhibition mRNA-1273 93.1%, BNT162b2 80.1%, AZD1222 38.5%, Ad26.CoV2.S 3.3%, Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Spike, Receptor Binding Domain (RBD), S1 domain, S2 domain and nucleocapsid) and the endemic coronaviruses (OC43, HKU1, NL63 and 229E). While samples were processed using an automated platform on a Beckman Coulter i7 pipetting robot as previously described ( 30 ) with minor modifications, all sample and reagent dilutions were already established and verified as part of the initial MULTICOV-AB technical assay validation process which is detailed in ( 28 ). Briefly, samples were thawed at room temperature, vortexed and then centrifuged at 2000 g for 3 mins to pellet any cell debris within the sample.…”

Section: Methodsmentioning

confidence: 99%

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Comparative Magnitude and Persistence of Humoral SARS-CoV-2 Vaccination Responses in the Adult Population in Germany

et al. 2022

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Recent increases in SARS-CoV-2 infections have led to questions about duration and quality of vaccine-induced immune protection. While numerous studies have been published on immune responses triggered by vaccination, these often focus on studying the impact of one or two immunisation schemes within subpopulations such as immunocompromised individuals or healthcare workers. To provide information on the duration and quality of vaccine-induced immune responses against SARS-CoV-2, we analyzed antibody titres against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and variants of concern in samples from a large German population-based seroprevalence study (MuSPAD) who had received all currently available immunisation schemes. We found that homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was particularly concerning with reduced titres and 91.7% of samples classified as non-responsive for ACE2 binding inhibition, suggesting that recipients require a booster mRNA vaccination. While mRNA vaccination induced a higher ratio of RBD- and S1-targeting antibodies, vector-based vaccines resulted in an increased proportion of S2-targeting antibodies. Given the role of RBD- and S1-specific antibodies in neutralizing SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why these vaccines have increased efficacy compared to vector-based formulations. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received, which could aid future dose allocation should shortages arise for certain manufacturers. Overall, both titres and ACE2 binding inhibition peaked approximately 28 days post-second vaccination and then decreased.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Comparative Magnitude and Persistence of Humoral SARS-CoV-2 Vaccination Responses in the Adult Population in Germany

et al. 2022

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“…In addition, children maintained antibody and cellular responses longer than 12 months, while adults showed a waning immune response at 6 months (Dowell et al ., 2022 ). German immunologists who analysed the immune response in 550 children and 700 adults observed no significant difference in antibody response between symptomatic and asymptomatic infections both for children and adults (Renk et al ., 2022 ).…”

Section: Introductionmentioning

confidence: 99%

COVID‐19 and children: medical impact and collateral damage

Brüssow

2022

Microbial Biotechnology

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Summary Children mostly experience mild SARS‐CoV‐2 infections, but the extent of paediatric COVID‐19 disease differs between geographical regions and the distinct pandemic waves. Not all infections in children are mild, some children even show a strong inflammatory reaction resulting in a multisystem inflammatory syndrome. The assessments of paediatric vaccination depend on the efficacy of protection conferred by vaccination, the risk of adverse reactions and whether children contribute to herd immunity against COVID‐19. Children were also the target of consequential public health actions such as school closure which caused substantial harm to children (educational deficits, sociopsychological problems) and working parents. It is, therefore, important to understand the transmission dynamics of SARS‐CoV‐2 infections by children to assess the efficacy of school closures and paediatric vaccination. The societal restrictions to contain the COVID‐19 pandemic had additional negative effects on children’s health, such as missed routine vaccinations, nutritional deprivation and lesser mother–child medical care in developing countries causing increased child mortality as a collateral damage. In this complex epidemiological context, it is important to have an evidence‐based approach to public health approaches. The present review summaries pertinent published data on the role of children in the pandemic, whether they are drivers or followers of the infection chains and whether they are (after elderlies) major sufferers or mere bystanders of the COVID‐19 pandemic.

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“…One mechanism thought to mediate protection is the development of neutralizing antibodies (nAb) to SARS-CoV-2, which have been shown to be predictive of protection from symptomatic COVID-19 infection 2 , and are often used as a correlate of protective immunity to SARS-CoV-2. While there are numerous studies of humoral immunity in adults, studies in children are limited, with conflicting results [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] . Two recent and large studies in children demonstrated that children develop neutralizing antibodies at similar levels and with similar duration to those seen adults after infection 8,12 .…”

Section: Introductionmentioning

confidence: 99%

“…While there are numerous studies of humoral immunity in adults, studies in children are limited, with conflicting results [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] . Two recent and large studies in children demonstrated that children develop neutralizing antibodies at similar levels and with similar duration to those seen adults after infection 8,12 . Yet in earlier studies, children with severe or mild to severe COVID-19 had lower nAb levels and duration than adults 4,11,17 .…”

Section: Introductionmentioning

confidence: 99%

Level and duration of IgG and neutralizing antibodies to SARS-CoV-2 in children with symptomatic or asymptomatic SARS-CoV-2 infection

Khaitan

Datta

Bond

et al. 2022

Preprint

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Background: There are presently conflicting data about level and duration of antibodies to SARS-CoV-2 in children after symptomatic or asymptomatic infection. Methods: We enrolled adults and children in a prospective 6-month study in the following categories: 1) symptomatic, SARS-CoV-2 PCR+ (SP+; children, n=8; adults, n=16), 2) symptomatic, PCR- or untested (children, n=27), 3) asymptomatic exposed (children, n=13) and 4) asymptomatic, no known exposure (children, n=19). Neutralizing and IgG antibodies to SARS-CoV-2 antigens and Spike protein variants were measured by multiplex serological assays. Results: All SP+ children developed nAb, whereas 81% of SP+ adults developed nAb. Decline in the presence of nAb over 6 months was not significant in symptomatic children (100% to 87.5%, p=0.32) in contrast to adults (81.3 to 50.0%, p=0.03). Among all children with nAb (n=22), nAb titers and change in titers over 6 months were similar in symptomatic and asymptomatic children. Levels of IgG antibodies in children to the SARS-CoV-2 Spike, RBD-1 and -2, nucleocapsid and N-terminal domain antigens and to Spike protein variants were similar to those in adults. IgG levels to primary antigens decreased over time in both children and adults, but levels to three of six Spike variants decreased only in children. Conclusions: Children with asymptomatic or symptomatic SARS-CoV-2 infection develop robust neutralizing antibodies that remain present longer than in adults but wane in titer over time, and broad IgG antibodies that also wane in level over time.

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Robust and durable serological response following pediatric SARS-CoV-2 infection

Cited by 67 publications

References 34 publications

Comparative Magnitude and Persistence of Humoral SARS-CoV-2 Vaccination Responses in the Adult Population in Germany

Comparative Magnitude and Persistence of Humoral SARS-CoV-2 Vaccination Responses in the Adult Population in Germany

COVID‐19 and children: medical impact and collateral damage

Level and duration of IgG and neutralizing antibodies to SARS-CoV-2 in children with symptomatic or asymptomatic SARS-CoV-2 infection

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