Hybrid Immunity in Sars-Cov-2: The Paediatric Story

Abstract

How many doses of mRNA SARS-CoV-2 vaccine should future birth cohorts of children take? Are boosters necessary for children? Current clinical guidelines on paediatric COVID-19 vaccination are largely extrapolated from experience from studies in adults; humoral and cellular immunogenicity of mRNA vaccines in children and their longevity, remain poorly defined. 

We recruited 145 seronegative healthy children 5 to 12 years of age, who were either vaccinated with 2 doses of 10mcg monovalent BNT162b2, or naturally infected, or both. We followed them up for 1 year, with longitudinal sampling of anti-Spike IgG, neutralising antibodies against ancestral virus and variants of concern, T cell responses, and memory B cells; this was compared to a mirror adult cohort. We characterized all symptomatic COVID-19, side effects of vaccination, and looked for asymptomatic COVID-19 with serological and T cell evidence, in order to differentiate vaccine-only (completed 2 doses) immunity (VV) from infection-only immunity, and hybrid immunity. 

We found that despite the lower dose of 10mcg of BNT162b2 compared to the 30mcg in adults, VV children had better antibody and T cell responses at 6 months. Among children with hybrid immunity, children with infection after 2 doses of vaccine (VVI) had higher neutralising antibody titres and T cell responses than children with infection between doses (VIV). Children with symptomatic VVI had higher neutralising antibody titres than those with asymptomatic VVI; however,  asymptomatic VVI had better T cell responses and showed a unique cytokine profile. A booster (third) dose elevated antibody but not T cell levels; the effect was more pronounced for VV children, but natural infection had the same effect in these. Dose 3 had more side effects than doses 1 and 2. 

Our data supports 2 doses of mRNA vaccination for children in an endemic COVID-19. In children with hybrid immunity, boosters are probably unnecessary. 

Note: This conference abstract was presented at the 17th Vaccine Conference organized by the journal Vaccine. This abstract has not been screened by SSRN for potential for public harm and should not be used to inform any clinical decision making. No competing interests or funding statements have been declared.