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SARS-CoV-2 mRNA vaccination elicits robust antibody responses in children.

ABSTRACT: Although children have been largely spared from coronavirus disease 2019 (COVID-19), the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) with increased transmissibility, combined with fluctuating mask mandates and school re-openings, have led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines to children of all ages. However, whether children respond equivalently to adults to mRNA vaccines and whether dosing will elicit optimal immunity remains unclear. Here we aimed to deeply profile the vaccine-induced humoral immune response in 6 to 11 year old children receiving either a pediatric (50 μg) or adult (100 μg) dose of the mRNA-1273 vaccine and to compare these responses to vaccinated adults, infected children, and children that experienced multisystem inflammatory syndrome in children (MIS-C). Children elicited an IgG-dominant vaccine-induced immune response, surpassing adults at a matched 100 μg dose, but more variable immunity at a 50 μg dose. Irrespective of titer, children generated antibodies with enhanced Fc-receptor binding capacity. Moreover, like adults, children generated cross-VOC humoral immunity, marked by a decline of omicron-specific receptor binding domain-binding, but robustly preserved omicron spike protein-binding. Fc-receptor binding capabilities were also preserved in a dose dependent manner. These data indicate that both the 50 μg and 100 μg doses of mRNA vaccination in children elicits robust cross-VOC antibody responses and that 100 μg doses in children results in highly preserved omicron-specific functional humoral immunity.

SUBMITTER: Bartsch YC

PROVIDER: S-EPMC9348753 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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SARS-CoV-2 mRNA vaccination elicits robust antibody responses in children.

Bartsch Yannic C YC St Denis Kerri J KJ Kaplonek Paulina P Kang Jaewon J Lam Evan C EC Burns Madeleine D MD Farkas Eva J EJ Davis Jameson P JP Boribong Brittany P BP Edlow Andrea G AG Fasano Alessio A Shreffler Wayne G WG Zavadska Dace D Johnson Marina M Goldblatt David D Balazs Alejandro B AB Yonker Lael M LM Alter Galit G

Science translational medicine 20221123 672

Although children have been largely spared from coronavirus disease 2019 (COVID-19), the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) with increased transmissibility, combined with fluctuating mask mandates and school reopenings, has led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines to children of all ages. However, whether children respond equivalently to adults to mRNA vacc ...[more]

PMID: 35881018

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Project description:The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has raised concerns about reduced vaccine effectiveness and the increased risk of infection, and while repeated homologous booster shots are recommended for elderly and immunocompromised individuals, they cannot completely protect against breakthrough infections. In our previous study, we assessed the immunogenicity of an adenovirus-based vaccine expressing SARS-CoV-2 S1 (Ad5.S1) in mice, which induced robust humoral and cellular immune responses (E. Kim, F. J. Weisel, S. C. Balmert, M. S. Khan, et al., Eur J Immunol 51:1774-1784, 2021, https://doi.org/10.1002/eji.202149167). In this follow-up study, we found that the mice had high titers of anti-S1 antibodies 1 year after vaccination, and one booster dose of the nonadjuvanted rS1Beta (recombinant S1 protein of SARS-CoV-2 Beta [B.1.351]) subunit vaccine was effective at stimulating strong long-lived S1-specific immune responses and inducing significantly high neutralizing antibodies against Wuhan, Beta, and Delta strains, with 3.6- to 19.5-fold increases. Importantly, the booster dose also elicited cross-reactive antibodies, resulting in angiotensin-converting enzyme 2 (ACE2) binding inhibition against spikes of SARS-CoV-2, including Omicron variants, persisting for >28 weeks after booster vaccination. Interestingly, the levels of neutralizing antibodies were correlated not only with the level of S1 binding IgG but also with ACE2 inhibition. Our findings suggest that the rS1Beta subunit vaccine candidate as a booster has the potential to offer cross-neutralization against broad variants and has important implications for the vaccine control of newly emerging breakthrough SARS-CoV-2 variants in elderly individuals primed with adenovirus-based vaccines like AZD1222 and Ad26.COV2.S. IMPORTANCE Vaccines have significantly reduced the incidences of severe coronavirus disease 2019 (COVID-19) cases and deaths. However, the emergence of SARS-CoV-2 variants has raised concerns about their increased transmissibility and ability to evade neutralizing antibodies, especially among elderly individuals who are at higher risks of mortality and reductions of vaccine effectiveness. To address this, a heterologous booster vaccination strategy has been considered as a solution to protect the elderly population against breakthrough infections caused by emerging variants. This study evaluated the booster effect of an S1 subunit vaccine in aged mice that had been previously primed with adenoviral vaccines, providing valuable preclinical evidence for elderly people vaccinated with the currently approved COVID-19 vaccines. This study confirms the potential for using the S1 subunit vaccine as a booster to enhance cross-neutralizing antibodies against emerging variants of concern.

Project description:BackgroundInfection during pregnancy can result in adverse outcomes for both pregnant persons and offspring. Maternal vaccination is an effective mechanism to protect both mother and neonate into post-partum. However, our understanding of passive transfer of antibodies elicited by maternal SARS-CoV-2 mRNA vaccination during pregnancy remains incomplete.ObjectiveWe aimed to evaluate the antibody responses engendered by maternal SARS-CoV-2 vaccination following initial and booster doses in maternal circulation and breastmilk to better understand passive immunization of the newborn.Study designWe collected longitudinal blood samples from 121 pregnant women who received SARS-CoV-2 mRNA vaccines spanning from early gestation to delivery followed by collection of blood samples and breastmilk between delivery and 12 months post-partum. During the study, 70% of the participants also received a booster post-partum. Paired maternal plasma, breastmilk, umbilical cord plasma, and newborn plasma samples were tested via enzyme-linked immunosorbent assays (ELISA) to evaluate SARS-CoV-2 specific IgG antibody levels.ResultsVaccine-elicited maternal antibodies were detected in both cord blood and newborn blood, albeit at lower levels than maternal circulation, demonstrating transplacental passive immunization. Booster vaccination significantly increased spike specific IgG antibody titers in maternal plasma and breastmilk. Finally, SARS-CoV-2 specific IgG antibodies in newborn blood correlated negatively with days post initial maternal vaccine dose.ConclusionVaccine-induced maternal SARS-CoV-2 antibodies were passively transferred to the offspring in utero via the placenta and after birth via breastfeeding. Maternal booster vaccination, regardless of gestational age at maternal vaccination, significantly increased antibody levels in breastmilk and maternal plasma, indicating the importance of this additional dose to maximize passive protection against SARS-CoV-2 infection for neonates and infants until vaccination eligibility.

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SARS-CoV-2 mRNA vaccination elicits robust antibody responses in children.

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SARS-CoV-2 mRNA vaccination elicits robust antibody responses in children.

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