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.

Live‐virus neutralization of the omicron variant in children and adults 14 months after SARS‐CoV‐2 wild‐type infection

“…This is in line with the conclusion of a recently published systematic review 33 . Cross variant neutralization against omicron has been reported to be even weaker after infection than after standard vaccination in children 28,34 . An increase in SARS‐CoV‐2 infections among vaccinated children and reports of acute myocarditis in adolescents and young adults following vaccination have led to vaccine hesitancy in children.…”

“…33 Cross variant neutralization against omicron has been reported to be even weaker after infection than after standard vaccination in children. 28,34 An increase in SARS-CoV-2 infections among vaccinated children and reports of acute myocarditis in adolescents and young adults following vaccination have led to vaccine hesitancy in children. However, myocarditis after standard vaccination is rare in children aged 5-11 years (1 in 1 million doses) 35 ;…”

Humoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination

“…However, IgG responses to the Omicron RBD were consistently lower post-vaccination for all subclasses and FcγRs (Fig. 3A, 3B), which is not unexpected given the large number of mutations in the RBD of Omicron in comparison to other variants and is consistent with cross-reactivity seen in older individuals 13,14 .…”

“…Thus, the risk/benefit ratio of vaccinating young children must be thoroughly analyzed; comprehensive profiling of the humoral immune response following vaccination, including characterization of antibody response profiles and crossprotective potential is critical. While in-depth antibody titers and effector function have been described for mRNA-vaccinated adults and children ages 5 years and older 13,14 , limited information exists for younger age groups.…”

Duration of immunity to SARS-CoV-2 in children after natural infection or vaccination in the omicron and pre-omicron era: A systematic review of clinical and immunological studies

“…investigated vaccine-induced humoral immune response in 6-to-11-years-old children and seems to confirm the importance of booster dose in previously infected paediatric population. Indeed vaccinated children elicited robust cross-VOC antibody responses and a 100 μg doses resulted in higher preserved Omicron-specific functional humoral immunity rather than those with diagnosed of COVID-19 or MIS-C ( 37 ). Importantly, a South Korean population cohort study of 3.2 million adolescents identified 29285 SARS-CoV-2 infection, 11 of which were classified as critical.…”