Impact of a booster dose on SARS-CoV2 mRNA vaccine-specific humoral-, B- and T cell immunity in pediatric stem cell transplant recipients

Front Immunol. 2023 Oct 24:14:1239519. doi: 10.3389/fimmu.2023.1239519. eCollection 2023.

Abstract

Stem cell transplant recipients (SCTR) are imperiled to increased risks after SARS-CoV2 infection, supporting the need for effective vaccination strategies for this vulnerable group. With respect to pediatric patients, data on immunogenicity of SARS-CoV2 mRNA-based vaccination is limited. We therefore comprehensively examined specific humoral, B- and T cell responses in a cohort of 2-19 year old SCTR after the second and third vaccine dose. Only after booster vaccination, transplant recipients reached similar levels of vaccine-specific IgG, IgA and neutralizing antibodies against omicron variant as age-matched controls. Although frequencies of SARS-CoV2 specific B cells increased after the third dose, they were still fourfold reduced in patients compared to controls. Overall, the majority of individuals enrolled mounted SARS-CoV2 Spike protein-specific CD4+ T helper cell responses with patients showing significantly higher portions than controls after the third dose. With respect to functionality, however, SCTR were characterized by reduced frequencies of specific interferon gamma producing CD4+ T cells, along with an increase in IL-2 producers. In summary, our data identify distinct quantitative and qualitative impairments within the SARS-CoV2 vaccination specific B- and CD4+ T cell compartments. More importantly, humoral analyses highlight the need for a booster vaccination of SCTR particularly for development of neutralizing antibodies.

Keywords: SARS-CoV2; antigen-specific immunity; cellular immunity; humoral immunity; mRNA vaccination; pediatrics; stem cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing
  • COVID-19* / prevention & control
  • Child
  • Child, Preschool
  • Humans
  • RNA, Viral*
  • SARS-CoV-2
  • Stem Cell Transplantation
  • Transplant Recipients
  • Vaccines, Synthetic
  • Young Adult
  • mRNA Vaccines

Substances

  • RNA, Viral
  • Vaccines, Synthetic
  • Antibodies, Neutralizing

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

KK is supported by grants from the Deutsche Forschungsgemeinschaft (KO-2270/7-1, KO-2270/4-1, KO-2270/8-1), Zentrales Innovationsprogramm Mittelstand (KK5463201BA2) and unconditional project funding from Chiesi GmbH. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. ES is enrolled in the Charité Clinician Scientist Program funded by the Charité–Universitätsmedizin Berlin and the Berlin Institute of Health. HS received funding from the Ministry for Science, Research, and Arts of Baden-Württemberg, Germany and the European Commission (HORIZON2020 Project SUPPORT-E, no. 101015756). This study received funding from Chiesi GmbH. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.