Abstract
In immunosuppressed (IS) adults, immune responses to SARS-CoV-2 mRNA vaccines were shown to be impaired. Given the reduced vaccine dosages approved for children under eleven years old, we investigated whether two doses of vaccines would suffice to protect children with immune deficiencies, or if an additional vaccine dose would be necessary for optimal protection. We recruited healthy children (n= 52) and children with primary (n=16) or secondary (n=14) antibody deficiency (SAD) and collected blood and saliva after each vaccine dose. Children were vaccinated following public health recommendations with a two-dose vaccination schedule for healthy children, and a three-dose schedule for IS children. After the second vaccine dose, IS children showed reduced circulating and neutralizing antibody (nAb) levels compared to their healthy counterparts. Importantly, the third vaccine dose significantly increased nAb titers in children with primary antibody deficiency to levels comparable to healthy children after two doses. In contrast, 79% of children with SAD did not develop nAb following vaccination. Interestingly, breakthrough (BT) infection induced a profound increase in nAbs in all children, including children with SAD, which will be further investigated through characterization of SARS-CoV-2-specific T and B cells. As a BT infection mimics a mucosal challenge, these results support the idea that mucosal vaccination strategies could emulate immune responses even in IS children.
