Human rhinovirus‐specific CD8 T cell responses target conserved and unusual epitopes

Gómez-Perosanz, Marta; Sanchez-Trincado, Jose L.; Fernández‐Arquero, Miguel; Sidney, John; Sette, Alessandro; Lafuente, Esther M.; Reche, Pedro A.

doi:10.1096/fj.202002165r

Cited by 7 publications

(28 citation statements)

References 51 publications

(120 reference statements)

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“…VP4 protein from RV A and whole consensus proteome from RV C were chosen as targets for CD4 T cell epitope prediction. The RV C consensus proteome was previously generated, as described by Gomez-Perosanz et al [ 18 ], upon sequence variability analysis of 39 RV C full proteomes using the Shannon Entropy (H) as a variability metric. The RV A peptides were 18-mer long, overlapping by 10 amino acids, and covered the entire VP4 protein of RV A with accession number NP_042288.1.…”

Section: Methodsmentioning

confidence: 99%

“…RV-specific T cells were expanded as described by Gomez-Perosanz et al [ 18 ]. Briefly, donors’ PBMCs were cultured at a density of 2 × 10 6 cells/mL in 24-well plates (BD Biosciences, Bedford, MA, USA) with RPMI 1640 (Gibco, Waltham, MA, USA), supplemented with 10% human serum (Gibco, Waltham, MA, USA), 100 µg/mL streptomycin, 100 U/mL penicillin, and 2 mM L-glutamine (Lonza, Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

“…Along with neutralizing antibodies, T cells also play a crucial role in the RV immunity [ 14 ], triggering both cellular and humoral immune responses. Interestingly, despite the low sequence identity among RV exposed capsid proteins, it has been shown that RV-specific CD4 and CD8 T cells can be reactive to multiple RV serotypes [ 15 , 16 , 17 , 18 ], revealing the presence of RV-specific conserved T cell epitopes. So far, only a few conserved RV-specific T epitopes have been identified [ 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, despite the low sequence identity among RV exposed capsid proteins, it has been shown that RV-specific CD4 and CD8 T cells can be reactive to multiple RV serotypes [ 15 , 16 , 17 , 18 ], revealing the presence of RV-specific conserved T cell epitopes. So far, only a few conserved RV-specific T epitopes have been identified [ 15 , 16 , 17 , 18 , 19 ]. A recent study [ 18 ] identified the first RV A and C conserved epitopes targeted by CD8 T cells, finding that they were distributed throughout the entire RV proteome, including proteins of the capsid and non-structural proteins.…”

Section: Introductionmentioning

confidence: 99%

“…So far, only a few conserved RV-specific T epitopes have been identified [ 15 , 16 , 17 , 18 , 19 ]. A recent study [ 18 ] identified the first RV A and C conserved epitopes targeted by CD8 T cells, finding that they were distributed throughout the entire RV proteome, including proteins of the capsid and non-structural proteins. Given the link between antigen recognition by B and T cells, CD4 T cell epitope mapping has mainly focused on external RV capsid proteins VP1, VP2, and VP3 (reviewed in Stepanova et al [ 20 ]), neglecting the remaining proteins.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Conserved and Promiscuous Human Rhinovirus CD4 T Cell Epitopes

Gómez-Perosanz

Fiyouzi

Fernández‐Arquero

et al. 2021

Cells

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Human rhinovirus (RV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from RV A and 8 from RV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in RV A and C serotypes and predicted to bind to multiple human leukocyte antigen class II (HLA II) molecules. We found positive T cell recall responses by interferon gamma (IFNγ)-ELISPOT assays to eight peptides, validating seven of them (three from RV A and four from RV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these seven epitopes could be recognized by >95% of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor RV infections and to develop peptide-based vaccines against most RV A and C serotypes.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Characterization of Conserved and Promiscuous Human Rhinovirus CD4 T Cell Epitopes

Gómez-Perosanz

Fiyouzi

Fernández‐Arquero

et al. 2021

Cells

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Molecular Characterization of the Viral Structural Genes of Human Rhinovirus A11 from Children Hospitalized with Lower Respiratory Tract Infection in Kunming

Zhang

Tan

Tang

et al. 2022

International Journal of Infectious Diseases

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Humoral and cellular immunogenicity and efficacy of a coxsackievirus A10 vaccine in mice

Liu

et al. 2023

Emerging Microbes & Infections

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Coxsackievirus A10 (CV-A10) has become one of the major pathogens of hand, foot and mouth disease (HFMD), and studies on the vaccine and animal model of CV-A10 are still far from complete. Our study used a mouse-adapted CV-A10 strain, which was lethal for 14-day-old mice, to develop an infected mouse model. Then this model was employed to establish an actively immunized-challenged mouse model to evaluate the efficacy of a formaldehyde-inactivated CV-A10 vaccine, which was prepared from a Vero cell-adapted strain. CV-A10 vaccine at a dose of 0.5 or 2.0 μg was inoculated intraperitoneally in neonatal Kunming mice on the third and ninth day. Then the mice were challenged on day 14. The survival rate of mice immunized with 0.5 or 2.0 μg vaccine were 90% and 100%, respectively, while all Alum-inoculated mice died. Compared to those in the two vaccinated groups, the Alum-inoculated mice showed severe pathological damage, strong viral protein expression and high viral loads. The antisera from vaccinated mice showed high level of neutralizing antibodies against CV-A10. Meanwhile, three potential T cell epitopes located at the carboxyl-terminal regions of the VP1 and VP3 were identified and exhibited CV-A10 serotype-specific. The humoral and cellular immunogenicity analysis showed that immunization with two doses of the vaccine elicited CV-A10 specific neutralizing antibody and T cell response in BALB/c mice. Collectively, these findings indicated that this actively immunized-challenged mouse model will be invaluable in future studies on CV-A10 pathogenesis and evaluation of vaccine candidates.

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Human rhinovirus‐specific CD8 T cell responses target conserved and unusual epitopes

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 7 publications

References 51 publications

Characterization of Conserved and Promiscuous Human Rhinovirus CD4 T Cell Epitopes

Characterization of Conserved and Promiscuous Human Rhinovirus CD4 T Cell Epitopes

Molecular Characterization of the Viral Structural Genes of Human Rhinovirus A11 from Children Hospitalized with Lower Respiratory Tract Infection in Kunming

Humoral and cellular immunogenicity and efficacy of a coxsackievirus A10 vaccine in mice

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