Immunogenicity and reactogenicity of SARS-CoV-2 mRNA and inactivated vaccines in healthy adolescents

Abstract

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.

Effectiveness of heterologous and homologous covid-19 vaccine regimens: living systematic review with network meta-analysis

“…When comparing vaccine effectiveness between age groups, we found people younger than 18 have a lower chance of covid-19 infection after receiving vaccines of any platform. This finding agrees with a recent immunogenicity study in children and adolescents 75. We also found that a heterologous or a homologous third dose booster can confer an equal level of protection in all age groups, even in the older group (≥65).…”

“…This finding agrees with a recent immunogenicity study in children and adolescents. 86 We also found that a heterologous or a homologous third dose booster can confer an equal level of protection in all age groups, even in the oldest age group (>65 years). If several boosters are to be administered to any age group, a heterologous or homologous regimen does not make much difference in improving immunity.…”

Omicron reactive multi protein specific CD4 T cells defines cellular immune response induced by inactivated virus vaccines

“…Our results are in contrast with previous observations by other groups that showed the ability of inactivated vaccines to induce both CD4 and CD8 T cell response but are however in line with other data of T cell response observed in other inactivated viral vaccines 52,53 . The difference appears to be due to the different method of analysis utilized by us and by the group in Hong-Kong 26 . The AIM assay utilized by them and by many groups worldwide (including us 29,42,54 ) is a powerful cellular technique that can define the phenotype of peptide responsive T cells.…”

“…These data suggest that inactivated vaccines might actually induce not only a weaker humoral response towards Spike but also an impaired level of T cell response which was however not experimentally supported. Analysis of SARS-CoV-2 specific T cells in individuals vaccinated with inactivated virus demonstrated the induction of T cells specific for Spike and other structural proteins (NP and Membrane) 25,26 and a magnitude of vaccine-induced CD8 T cells that were superior to the Spike-specific CD8 T cells induced by mRNA vaccines 26 . Such strong induction of CD8 T cell response was perplexing since the antigen processing and presentation pathway associated with an exogenous protein antigen like inactivated SARS-CoV-2 vaccine is expected to induce primarily a CD4 T cell response 27 .…”