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

Author:

Parker Rebecca S.1,Le Justin1,Villa Miguel1,Luong Annie2,Lin Tsen Yin2,Lee Yesun34,Doan Andrew15,Aguayo‐Hiraldo Paibel15,Pannaraj Pia S.34,Yoon Seon‐Jae1,Wallace William Dean6,Armstrong April6,O'Gorman Maurice R.567,Bard Jennifer Dien7,Parekh Chintan15ORCID

Affiliation:

1. Children's Center for Cancer and Blood Disease Children's Hospital Los Angeles California Los Angeles USA

2. The Saban Research institute Children's Hospital Los Angeles California Los Angeles USA

3. Division of Infectious Diseases Children's Hospital Los Angeles California Los Angeles USA

4. Department of Pediatrics University of California San Diego San Diego California USA

5. Department of Pediatrics, Keck School of Medicine University of Southern California Los Angeles California USA

6. Department of Pathology, Keck School of Medicine University of Southern California Los Angeles California USA

7. Department of Pathology and Laboratory Medicine Children's Hospital Los Angeles Los Angeles California USA

Abstract

AbstractLittle 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.

Funder

Saban Research Institute

Concern Foundation

National Center for Advancing Translational Sciences

W. M. Keck Foundation

Children's Cancer Research Fund

Publisher

Wiley

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