Binding and neutralizing antibody responses to SARS-CoV-2 in very young children exceed those in adults

Area of Science:

• Immunology
• Virology
• Pediatrics

Background:

• SARS-CoV-2 infections present with varying severity, often milder in children compared to adults.
• Age-related differences in immune responses to SARS-CoV-2 are suspected but not well-characterized in young children.
• Limited data exists on the specific immune profiles of SARS-CoV-2 infection in pediatric populations.

Purpose of the Study:

• To compare SARS-CoV-2 antibody responses, specifically receptor binding domain-binding antibody (RBDAb) and neutralizing antibody titers, between young children (0-4 years), older children (5-17 years), and adults.
• To investigate potential age-dependent variations in the immune response to SARS-CoV-2 infection.
• To evaluate the implications of these findings for assessing COVID-19 vaccine immunogenicity in young children.

Main Methods:

• A prospective longitudinal household study design was employed to track SARS-CoV-2 infection.
• Serum specimens from seropositive participants across different age groups (0-4, 5-17, and 18-62 years) were analyzed.
• Receptor binding domain-binding antibody (RBDAb) titers and SARS-CoV-2-neutralizing antibody titers were measured using pseudovirus-neutralizing antibody assays.

Main Results:

• Children aged 0-4 years demonstrated over 10-fold higher RBDAb titers compared to adults (416 vs. 31, P < 0.0001).
• Young children exhibited the highest RBDAb titers in most households with mixed age seropositivity.
• While neutralizing antibody titers were only 2-fold higher in young children, their binding-to-neutralizing antibody ratios were significantly elevated compared to adults (2.36 vs. 0.35, P = 0.0004).

Conclusions:

• Young children (0-4 years) mount substantial and robust antibody responses following SARS-CoV-2 infection.
• The distinct antibody profile in young children, characterized by high binding and moderate neutralizing antibodies, warrants consideration.
• These findings support the use of neutralizing antibody assays for evaluating the immunogenicity of COVID-19 vaccines in the youngest pediatric age group.