Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents

接种疫苗的儿童和青少年在 COVID-19 突破性病例中的免疫反应

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作者:Daniela Rivera-Pérez #, Constanza Méndez #, Benjamín Diethelm-Varela, Felipe Melo-González, Yaneisi Vázquez, Xing Meng, Qianqian Xin, Rodrigo A Fasce, Jorge Fernández, Judith Mora, Eugenio Ramirez, Mónica L Acevedo, Fernando Valiente-Echeverría, Ricardo Soto-Rifo, Alba Grifoni, Daniela Weiskopf, Ale

Background

Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus.

Conclusion

SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical

Methods

Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay.

Results

2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects.

Trial registration

clinicaltrials.gov #NCT04992260.

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