ABSTRACT
Background: Patients with kidney diseases are at risk of severe complications from COVID-19, yet little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. Methods: We investigated the immunogenicity and safety of an accelerated, 3-dose primary series of COVID-19 vaccines among 64 pediatric chronic kidney disease patients (mean age 12.2; 32 male) with or without immunosuppression, dialysis, or kidney transplant. CoronaVac was given to those aged <5 years, 0.1ml BNT162b2 to those aged 5-11 years, and 0.3ml BNT162b2 to those aged 11-18 years. Results: Antibody responses including S-RBD IgG (90.9-100% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6-94.0%) were significantly elicited by 3 doses of any vaccine. T cell responses were also elicited. Weaker neutralization responses were observed among kidney transplant recipients and non-dialysis children receiving rituximab for glomerular diseases. Neutralization was reduced against Omicron BA.1 compared to wild-type (post-dose 3 sVNT% level; 84% vs 27.2%; p<0.0001). However, T cell response against Omicron BA.1 was preserved, which likely confer protection against severe COVID-19. Hybrid immunity was observed after vaccination in infected patients, as evidenced by higher Omicron BA.1 neutralization response among infected patients receiving 2 doses than those uninfected. Generally mild or moderate adverse reactions following vaccines were reported. Conclusions: Our findings support that an accelerated 3-dose primary series with CoronaVac and BNT162b2 is safe and immunogenic in young children and adolescents with kidney diseases.
Subject(s)
Infections , Kidney Diseases , COVID-19 , Renal Insufficiency, ChronicABSTRACT
High effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 6 months after 2 doses, S IgG, S IgG Fc receptor-binding, S-RBD IgG and neutralizing antibody responses waned significantly, yet neutralizing antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ+ and IL-2+ CD8+ T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ+ and IL-2+ CD4+ and CD8+ T cell responses in adolescents and adults were comparable. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, and PRNT50 against Omicron BA.2, as well as preserved cellular responses against BA.1 S. Sera from 100% and 96% of adolescents tested at 1 and 6 months after 2 doses could also neutralize BA.1. Based on PRNT50, we predict 92%, 89% and 68% effectiveness against COVID-19 with WT, BA.2 and BA.5 1 month after 3 doses. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after 3 doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.
Subject(s)
COVID-19ABSTRACT
For SARS-CoV-2 vaccines, efficacy data for BNT162b2 but not CoronaVac are available in adolescents. Phase II/III studies focused on neutralizing antibody responses in adolescents, neglecting binding antibody and cellular responses that are also important against SARS-CoV-2. Therefore, we conducted a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of these 2 vaccines in healthy adolescents. One-dose BNT162b2 outcomes were also assessed since it had been recommended in some localities due to the risk of myocarditis. Antibodies and T cell immune responses were non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB, N=116) and CoronaVac (CC, N=123) versus adults after 2 doses of the same vaccine (BB, N=147; CC, N=141) but not in adolescents after 1 dose of BNT162b2 (B, N=116). CC induced SARS-CoV-2 nucleocapsid (N) and N C-terminal domain seroconversion in more adolescents than adults. Adverse reactions were mostly mild for both vaccines and more frequent for BNT162b2. We confirmed higher S, neutralizing, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC. This is the first study to show similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2 in adolescents. The implications of the differential ability to induce S- and non-S-specific antibody and T cell responses on the durability of protection and protection against virus variants by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines in the world, should be further investigated. Our results support the use of both vaccines in adolescents.