In a recent study published on the bioRxiv* preprint server, researchers assessed the antibody response and cellular immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infection in children
Study: Primary Omicron infection elicits weak antibody response but robust cellular immunity in children. Image credit: FamVeld/Shutterstock
Infection rates associated with the Omicron variant SARS-CoV-2 have been consistently high across all age groups. The seroprevalence of SARS-CoV-2 among children has increased markedly from 40% to 82% after the emergence of Omicron. Therefore, extensive research is needed to understand the extent of the immune response induced by Omicron infection in younger populations.
About the study
In the present study, the researchers examined the cellular and antibody immune response elicited after infection with the SARS-CoV-2 Omicron variant among children aged six to 14 years and compared the results with infection and previous coronavirus disease 2019 (COVID-19) vaccination status.
The team evaluated the neutralizing capacity of sera obtained from individuals who reported natural infection with SARS-CoV-2 variants, which were prevalent before Omicron. We estimated the binding capacity of antibodies to the spike (S) and receptor-binding domain (RBD) regions of wild-type and Omicron SARS-CoV-2 in serological samples collected from 54 children from five and 15 years old, infected with a pre-Omicron variant. . These estimates were compared with those of 30 adult participants and unvaccinated adults and children.
The team also recruited 43 unvaccinated children with a positive SARS-CoV-2 result obtained during the Omicron wave of infections. Antibody response after primary or secondary infection was determined. Primary infections were cases with Omicron as the first exposure to COVID-19, and secondary infections were cases with prior infection with the pre-Omicron variant. In addition, the team determined serological responses after primary and secondary infection among the children.
Functional humoral immunity was also estimated with a pseudovirus-based neutralization assay performed after primary and secondary Omicron infection. In addition, the team recruited 32 children between the ages of six and 14 who were vaccinated with the BNT162b2 COVID-19 vaccine, including ten dual-vaccinated children and 22 singly-vaccinated children.
results
The results of the study showed that the relative binding activity of antibodies to SARS-CoV-2 Omicron S and RBD was markedly decreased in children and adults compared to that of the wild-type strain. Relative binding decreased by 85% in children and 88% in adults, while only 41% showed a positive RBD response. This indicated that recognition of Omicron by serum antibodies after a pre-Omicron infection was markedly reduced in children and adults.
The team noted that primary Omicron infection induced low levels of antibody response against pre-Omicron and Omicron variants. Antibody titers were notably higher against the SARS-CoV-2 Delta variant in one of the children tested. On the other hand, secondary Omicron infection stimulated a robust antibody response against all pre-Omicron variants with an eight-fold increase against wild-type RBD and a 10-fold increase against Omicron RBD. However, the reduction in Omicron-specific titers compared to the previous variants was consistent despite an Omicron infection.
Primary Omicron infection was also found to induce comparable and low levels of antibody response against pre-Omicron and Omicron variants. Notably, the pre-Omicron titers were 22% of those observed in the historical group of pre-Omicron patients. However, secondary Omicron infection increased antibody responses elicited against all viral variants. Nucleocapsid-specific responses were comparatively lower after primary Omicron infection than after secondary infection.
Furthermore, primary Omicron infection resulted in weak neutralizing activity, whereas only 53% of infected children showed detectable neutralizing titers despite a previous infection. On the other hand, robust neutralization was observed after secondary infection with measurable neutralization titers.
Dual vaccination induced robust antibody responses against SARS-CoV-2 S and RBD related to all SARS-CoV-2 variants. Some variation was observed among children vaccinated with a single dose and reflected prior infection. Responses against Omicron S were decreased by 74% and RBD by 79% compared to wild type. Furthermore, the levels of S-specific antibodies observed were 7.3-fold higher after single vaccination and 19-fold higher after dual vaccination against wild-type than after natural pre-Omicron infection. Furthermore, Omicron-specific antibody responses did not increase after infection and were 71% lower compared to the wild-type strain.
Notably, antibody titers specific to pre-Omicron and Omicron spike proteins were markedly increased after vaccination, indicating the impact of hybrid immunity. Omicron-specific relative titers were also found to be consistent even after using wild-type S immunogen. This suggested that primary Omicron infection primed the humoral immune response for a robust response to vaccination while retaining comparatively equivalent recognition against the Omicron variant.
Overall, the findings of the study showed that primary infection with SARS-CoV-2 Omicron elicited a modest antibody response and little neutralizing activity. The researchers believe that although the COVID-19 vaccine showed strong immunogenicity in children, the effectiveness of the vaccine is affected by history of infection with Omicron or a pre-Omicron variant.
*Important news
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.