COVID-19 Moderna vaccine induces significant antibody reactions among children

By Shanet Susan AlexJul 28 2022Reviewed by Aimee Molineux

In a recent article published in the Science Translational Medicine journal, researchers illustrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid (mRNA) vaccination triggers potent antibody reactions in children.

Background

As the immune systems of young children are still developing and untrained, they frequently have a higher burden of respiratory infections. Although Coronavirus disease 2019 (COVID-19) incidence was rare in children, the appearance of SARS-CoV-2 variants of concern (VOC) with greater transmissibility, like Omicron, along with school re-openings and shifting mask regulations, have increased SARS-CoV-2 infections in children. Therefore, it is crucial to vaccinate children of all ages against COVID-19.

Nevertheless, it is yet unknown whether children react to SARS-CoV-2 mRNA vaccinations like adults and whether the recommended dosage will produce the optimum immunity.

About the study

In the present work, the researchers sought to characterize the humoral immune reaction induced by an adult (100 μg) or pediatric (50 μg) dose of the COVID-19 Moderna mRNA-1273 vaccine in children aged six to 11. They compared these reactions to SARS-CoV-2-infected children, vaccinated adults, and children who had multisystem inflammatory syndrome in children (MIS-C).

Moreover, the subjects received two shots of 100 and 50 μg doses of the Moderna vaccine. Plasma samples were taken before vaccination (V0), around four weeks after the first vaccine (V1), and four weeks post the second vaccination (V2).

The scientists examined SARS-CoV-2 spike (S) protein-specific antibody titers to assess the vaccine-triggered humoral response. They characterized the relative potential of vaccine-elicited immune reactions to attach to human fragment crystallizable (Fc)-receptors (FcγR2b, FcγR2a, FcγR3a, FcαR, and FcγR3b). Additionally, the researchers explored how well they could trigger antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent complement deposition (ADCD), antibody-dependent natural killer cell activation (ADNKA), or antibody-dependent monocyte phagocytosis (ADCP).

The authors then looked at vaccine-elicited Fc-effector activities to see if these different pediatric Fcγ-receptor attachment patterns translated to more functional humoral immune reactions that were selective for S proteins. In addition, they used a machine learning strategy to investigate the characteristics of the humoral immunity that varied most between adults and children at matched doses or children receiving the 50 μg and 100 μg doses to more precisely understand the variances in immune reactions among these groups. The team also analyzed if mRNA vaccination in children produced immune reactions with distinct capacities for recognizing SARS-CoV-2 VOCs.

Results

According to the study results, 12 children received a 100 μg, i.e., adult dose, of the Moderna vaccine with a median age of nine years ranging from seven to 11 years, and 42% were female, in line with adult dosage recommendations. Further, another 12 children received a 50 μg, i.e., pediatric dose, of mRNA-1273 with a median age of eight years ranging from six to 11 years, and 50% were female. Furthermore, the children in both cohorts were vaccinated at days 0 and 28, respectively.

The authors noted that the Moderna vaccine 50 μg and 100 μg doses were well tolerated comparably. Fever, injection site pain, and fatigue were typical minor vaccination-related side effects.

The Moderna mRNA vaccine was significantly immunogenic in six to 11-year-old children, producing a humoral reaction that was superior to what was observed after virus exposure. Granular vaccine-elicited humoral characterization revealed differences between pediatric and adult vaccine responses, with preferential induction of significantly functional immunoglobulin G (IgG) reactions and fewer IgM and IgA reactions in children relative to adults. Children mounted potent opsonophagocytic activities and Fcγ-receptor binding reactions at an adult-matching 100 μg dose. Moreover, children displayed comparable, albeit more diverse, responses relative to adults at 50% of the adult dose.

The team observed a significant induction of immunity targeting most SARS-CoV-2 VOCs, except for the Omicron variant. Although children vaccinated with the 100 μg dose harbored IgG with greater identification of the Omicron S protein compared to adults immunized with the 100 μg dose and children vaccinated with the 50 μg dose, IgG and Fc-receptor attachment profiles were very similar between children and adults. Children in the 50 μg dose group showed lower cross-VOC recognition, whereas children in the 100 μg dose group showed immune responses with an enhanced cross-VOC breadth.

Conclusions

Overall, the study findings depicted that children vaccinated with 100 μg of COVID-19 Moderna vaccine demonstrated 100% vaccine response rates before the second vaccine shot. On the other hand, immunological patterns in the low (50 μg) dose vaccinated children were more comparable to those in 100 μg vaccinated adults (the adult-recommended vaccine dose).

Besides, children exhibited an IgG-dominant vaccine-elicited immune reaction that was greater than adults at a comparable 100 μg dose but less consistent at a 50 μg dose. Children developed antibodies with increased Fc-receptor attachment capability regardless of titer. 

Moreover, children developed cross-VOC humoral immunity similar to adults, accompanied by a reduction in the attachment of Omicron-specific receptor-binding domains (RBD) but robust preservation of Omicron S protein-adhesion. Additionally, the capacity to bind Fc-receptor was maintained in a dose-reliant way.

On the whole, the study data suggest that COVID-19 mRNA vaccination in children at doses of 50 and 100 μg results in strong cross-VOC antibody reactions and highly retained Omicron-specific functional humoral immunity. The current findings show that the mRNA-1273 vaccine induces robust yet dose-reliant functional humoral pediatric immunological responses in children.