COVID-19 vaccinated children, adolescents, and young adults with acute lymphoblastic leukemia show spike reactive antibodies and multifunctional T-cells

Int J Cancer. 2024 Dec 15;155(12):2190-2200. doi: 10.1002/ijc.35096. Epub 2024 Jul 15.

Abstract

Little is known about the efficacy of COVID-19 vaccines during acute lymphoblastic leukemia therapy (ALL); data for COVID-19 vaccine immune responses in pediatric leukemia remain sparse. We conducted a single center study of patients aged 5-25 years undergoing ALL chemotherapy who received COVID-19 vaccination. Twenty-one patients were enrolled; efficacy was evaluable in 20. Twenty were vaccinated while receiving chemotherapy. Twenty received the BNT162b2 mRNA vaccine. Spike reactive antibodies (S-IgG) and/or T-cells (SRT) were detected in 16 of 20 (80%) vaccinated patients; 13 (65%) and 9 (45%) were positive for S-IgG and SRT, respectively. Six (30%) showed both spike reactive B and T-cell responses. Eleven of the 13 with S-IgG positivity were negative for anti-Nucleocapsid IgG, an antibody profile consistent with a vaccine induced immune response. All 13S-IgG+ patients showed neutralizing antibodies. SRT included CD4+ (7) and CD8+ (6) T-cells; both CD4+ and CD8+ SRT were seen in 4. SRT were multifunctional (producing multiple cytokines) in most patients (8 of 9); 4 showed SRT with triple cytokine and B-cell co-stimulatory responses, indicating a multimodal adaptive immune response. Immune responses were seen among patients vaccinated in the settings of lymphopenia (6 of 12) intensive chemotherapy (3 of 4), and Peg allergy (6 of 8). Sequencing revealed public CD4+ and CD8+ TCR sequences reactive to epitopes across the spike protein. In conclusion, COVID-19 vaccination induced B and/or T-cell responses in a majority of children and young adults undergoing ALL chemotherapy.

Keywords: COVID‐19 vaccine; T‐cell response; pediatric ALL.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral* / immunology
  • BNT162 Vaccine* / administration & dosage
  • BNT162 Vaccine* / immunology
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / immunology
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes / immunology
  • Vaccination
  • Young Adult

Substances

  • COVID-19 Vaccines
  • Antibodies, Viral
  • BNT162 Vaccine
  • Spike Glycoprotein, Coronavirus
  • Antibodies, Neutralizing
  • spike protein, SARS-CoV-2
  • Immunoglobulin G