Spike protein is a key target for stronger and more persistent T-cell responses-a study of mild and asymptomatic SARS-CoV-2 infection.

Hematological parameters IFN-γ Immunodominance Long-term immunity Mild and asymptomatic COVID-19 Spike protein

Journal

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
ISSN: 1878-3511
Titre abrégé: Int J Infect Dis
Pays: Canada
ID NLM: 9610933

Informations de publication

Date de publication:
Nov 2023
Historique:
received: 22 05 2023
revised: 08 08 2023
accepted: 02 09 2023
medline: 27 10 2023
pubmed: 9 9 2023
entrez: 8 9 2023
Statut: ppublish

Résumé

Understanding the immune response in very mild and asymptomatic COVID-19 is crucial for developing effective vaccines and immunotherapies, yet remains poorly characterized. This longitudinal study examined the evolution of interferon (IFN)-γ responses to SARS-CoV-2 peptides in 109 asymptomatic or mildly symptomatic Ugandan COVID-19 patients across 365 days and explored their association with antibody generation. T-cell responses to spike-containing clusters of differentiation (CD4)-S and CD8 nCoV-A (CD8-A) megapools, and the non-spike CD4-R and CD8 nCoV-B (CD8-B) megapools, were assessed and correlated with demographic and temporal variables. SARS-CoV-2-specific IFN-γ responses were consistently detected in all peptide pools and time points, with the spike-targeted response exhibiting higher potency and durability than the non-spike responses. Throughout the entire 365-day infection timeline, a robust positive correlation was observed between CD4 T-cell responses to the spike-derived peptides and anti-spike immunoglobulin G antibody levels, underscoring their interdependent dynamics in the immune response against SARS-CoV-2; in contrast, CD8 T-cell responses exhibited no such correlation, highlighting their distinctive, autonomous role in defense. No meaningful variations in complete blood count parameters were observed between individuals with COVID-19 infection and those without, indicating clinical insignificance. This study highlights the dominant role of spike-directed T-cell responses in mild and asymptomatic disease and provides crucial longitudinal data from Sub-Saharan African settings. The findings provide valuable insights into the dynamics of T-cell responses and their potential significance in developing effective strategies for combating COVID-19.

Identifiants

pubmed: 37683720
pii: S1201-9712(23)00714-2
doi: 10.1016/j.ijid.2023.09.001
pii:
doi:

Substances chimiques

spike protein, SARS-CoV-2 0
Spike Glycoprotein, Coronavirus 0
Interferon-gamma 82115-62-6
Antibodies, Viral 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

49-56

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declarations of competing interest The authors have no competing interests to declare.

Auteurs

Ivan Ssali (I)

Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda.

Susan Mugaba (S)

Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda.

Arthur Kalyebi Watelo (AK)

Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.

Juliana Bemanzi (J)

Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.

Joseph Ssebwana Katende (JS)

Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda; Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.

Gerald Kevin Oluka (GK)

Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda; Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.

Violet Ankunda (V)

Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda.

Claire Baine (C)

Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.

Laban Kato (L)

Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda.
Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda; Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.

Nathan Onyachi (N)

Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda.

Moses Muwanga (M)

Department of Internal Medicine, Entebbe Regional Referral Hospital, Entebbe, Uganda.

Mark Jjuuko (M)

Department of Internal Medicine, Masaka Regional Referral Hospital, Masaka, Uganda.

John Kayiwa (J)

Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.

Christopher Nsereko (C)

Department of Internal Medicine, Entebbe Regional Referral Hospital, Entebbe, Uganda.

Betty Oliver Auma (BO)

Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda.

Daniela Weiskopf (D)

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, USA.

Alessandro Sette (A)

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, USA.

Tom Lutalo (T)

Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.

Monica Musenero (M)

Science, Technology, and Innovation Secretariat, Office of the President, Government of Uganda, Kampala, Uganda.

Pontiano Kaleebu (P)

Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda; Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.

Jennifer Serwanga (J)

Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda; Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda. Electronic address: Jennifer.Serwanga@mrcuganda.org.

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Classifications MeSH