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

Front Immunol. 2024 May 15:15:1372193. doi: 10.3389/fimmu.2024.1372193. eCollection 2024.

Abstract

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.

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.

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 trial registration: clinicaltrials.gov #NCT04992260.

Keywords: CoronaVac®; SARS-CoV-2; breakthrough cases; inactivated SARS-CoV-2 vaccine; omicron variant; pediatric; phase 3 clinical trial.

MeSH terms

  • Adolescent
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • CD4-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Child
  • Child, Preschool
  • Cytokines / blood
  • Cytokines / immunology
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Male
  • SARS-CoV-2* / immunology
  • Vaccination

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Cytokines
  • Immunoglobulin G

Supplementary concepts

  • SARS-CoV-2 variants

Associated data

  • ClinicalTrials.gov/NCT04992260

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The PedCoronaVac03CL Study was funded by Sinovac Biotech and supported by the National Agency for Research and Development (ANID) through Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) grants 1190156, 1211547, and 1190830 which support R.S-R., F.V-E., and A.M.K., respectively, the Millennium Institute on Immunology and Immunotherapy (MIII), ANID-Millennium Science Initiative Program ICN2021_045 (formerly ICN09_016 and P09/016-F), which supports A.M.K., P.A.G., S.M.B, R.S-R., F.V-E., and K.A., and The Innovation Fund for Competitiveness FIC-R 2017 (BIP code 30488811-0) supporting S.M.B., P.A.G., and A.M.K. Study reagents for immunogenicity assays were funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. 75N93021C00016 to A.S. and contract no. 75N93019C00065 to A.S. and D.W.