Immunogenicity against wild-type and Omicron SARS-CoV-2 after a third dose of inactivated COVID-19 vaccine in healthy adolescents

Abstract

IntroductionTwo doses of inactivated SARS-CoV-2 vaccine CoronaVac cannot elicit high efficacy against symptomatic COVID-19, especially against the Omicron variant, but that can be improved by a third dose in adults. The use of a third dose of CoronaVac in adolescents may be supported by immunobridging studies in the absence of efficacy data.MethodsWith an immunobridging design, our study (NCT04800133) tested the non-inferiority of the binding and neutralizing antibodies and T cell responses induced by a third dose of CoronaVac in healthy adolescents (N=94, median age 14.2 years, 56% male) compared to adults (N=153, median age 48.1 years, 44% male). Responses against wild-type (WT) and BA.1 SARS-CoV-2 were compared in adolescents. Safety and reactogenicity were also monitored.ResultsA homologous third dose of CoronaVac further enhanced antibody response in adolescents compared to just 2 doses. Adolescents mounted non-inferior antibody and T cell responses compared to adults. Although S IgG and neutralizing antibody responses to BA.1 were lower than to WT, they remained detectable in 96% and 86% of adolescents. T cell responses to peptide pools spanning only the mutations of BA.1 S, N and M in adolescents were preserved, increased, and halved compared to WT respectively. No safety concerns were identified.DiscussionThe primary vaccination series of inactivated SARS-CoV-2 vaccines for adolescents should include 3 doses for improved humoral immunogenicity.

Superior antibody and membrane protein-specific T cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

“…1,5,12 Moreover, we were able to estimate actual vaccine efficacies using neutralising antibodies. 14,16,31 The comprehensive, validated assays of antibody levels, avidity and binding and T cell responses were a major strength of this study, yet follow-up research on clinical efficacy and real-life effectiveness against COVID-19 from ID would be needed to further support the current findings. The sample size for the ID group was slightly smaller than the initial target due to the unforeseeable wave of Omicron infections that swept across HK during the study period that doses 2 and 3 were administered.…”

“…CoronaVac in adolescents and children, as previously described. 14,16,39 The current pre- Procedures. Study doctors obtained informed assent from eligible participants and consent from their respective parents or legally acceptable representatives.…”

“…Hence, we extrapolated our PRNT50 results from evaluable adolescents who received 2 or 3 doses of IM or ID CoronaVac with vaccine efficacies against symptomatic COVID-19 by normalization to convalescent sera, as previously described. 14,16,31 The mean neutralisation levels of IM-CC, ID-CC, IM-CCC and ID-CCC were 0.19, 0.22, 0.40 and 0.79, corresponding to 49%, 52%, 66% and 79% vaccine efficacies, respectively (Fig. 3).…”

“…Participants were required to report pre-specified adverse reactions (ARs) in an online or handwritten diary for the following 7 days, as previously described. 14,16 They were encouraged to capture photos of their sites of injection for at least 7 days and until resolution of local reactions, followed by uploading onto our online diary website. Unsolicited adverse events (AEs), such as hospitalisation, life-threatening illnesses, disabilities, deaths, birth defects of offspring and breakthrough COVID-19 are monitored for 3 years.…”

“…15 In our recent study, the immunogenicity of CoronaVac against Omicron was markedly lower than the wild type (WT) strain in adolescents. 16 As a result of immune evasion by these VOCs and waning antibodies, inclusion of the third dose as part of the primary series of CoronaVac had been recommended in Hong Kong and Singapore for most age groups. It is apparent that all feasible strategies on optimizing immunological responses to CoronaVac need to be urgently explored.…”