Journal article
A T cell-based SARS-CoV-2 spike protein vaccine provides protection without antibodies
JCI insight, Vol.9(5), e155789
03/08/2024
DOI: 10.1172/jci.insight.155789
PMCID: PMC10972590
PMID: 38456504
Abstract
SARS-CoV-2 spike-based vaccines are used to control the COVID-19 pandemic. However, emerging variants have become resistant to antibody neutralization and further mutations may lead to full resistance. We tested whether T cells alone could provide protection without antibodies. We designed a T cell-based vaccine in which SARS-CoV-2 spike sequences were rearranged and attached to ubiquitin. Immunization of mice with the vaccine induced no specific antibodies, but strong specific T cell responses. We challenged mice with SARS-CoV-2 wild-type strain or an Omicron variant after the immunization and monitored survival or viral titers in the lungs. The mice were significantly protected against death and weight loss caused by the SARS-CoV-2 wild-type strain, and the viral titers in the lungs of mice challenged with the SARS-CoV-2 wild-type strain or the Omicron variant were significantly reduced. Importantly, depletion of CD4+ or CD8+ T cells led to significant loss of the protection. Our analyses of spike protein sequences of the variants indicated that fewer than one-third presented by dominant HLA alleles were mutated and that most of the mutated epitopes were in the subunit 1 region. As the subunit 2 region is conservative, the vaccines targeting spike protein are expected to protect against future variants due to the T cell responses.
Details
- Title: Subtitle
- A T cell-based SARS-CoV-2 spike protein vaccine provides protection without antibodies
- Creators
- Juan Shi - Georgia State UniversityJian Zheng - University of IowaXiujuan Zhang - New York Blood CenterWanbo Tai - New York Blood CenterRyan Compas - Loyola University ChicagoJack Deno - Loyola University ChicagoNatalie Jachym - Loyola University ChicagoAbhishek K Verma - University of IowaGang Wang - Georgia State UniversityXiaoqing Guan - Georgia State UniversityAbby E Odle - University of IowaYushun Wan - University of Minnesota Medical SchoolFang Li - University of MinnesotaStanley Perlman - University of IowaLiang Qiao - Loyola University ChicagoLanying Du - Georgia State University
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.9(5), e155789
- DOI
- 10.1172/jci.insight.155789
- PMID
- 38456504
- PMCID
- PMC10972590
- NLM abbreviation
- JCI Insight
- eISSN
- 2379-3708
- Grant note
- name: NIH, award: R01 AI157975, R01AI139092, from NIH
- Language
- English
- Date published
- 03/08/2024
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984567870202771
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