Predicting Immunogenic CD4+ T Cell Epitopes in Bacteria Using Antigen and Peptide Features DOI Creative Commons
Daniel Marrama, Hannah Battey, Ehdieh Khaledian

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract Background T cell epitope prediction methods have been broadly utilized to facilitate discovery in infectious agents and help design reagents, diagnostics, vaccines. Current are mainly focused on peptide presentation by MHC molecules, which is a necessary but not sufficient requirement for an epitope. For complex pathogens such as bacteria, it would be desirable make predictions more specific limit the number of candidates that experimentally tested. Objective To develop machine learning-based model integrates both peptide-level antigen-level features improve specificity CD4+ bacteria. Methods We used dataset 20,216 peptides from Mycobacterium tuberculosis (Mtb), tested recognition Mtb-infected participants, led n = 144 epitopes. each peptide, we calculated six (e.g. class II binding conservation scores) including RNA expression levels subcellular localization scores). Three learning algorithms—Random Forest, Gradient Boosting, XGBoost—were trained using stratified, 5-fold cross-validation combined into ensemble model. Experimental validation was performed Streptococcus pneumoniae peptides, ex vivo IFNγ assays confirm predictive performance. Results The achieved ROC-AUC 0.91 predicting immunogenic (Mtb) dataset. Gene were identified most impactful features, followed predictions. When validated independent Bordetella pertussis dataset, demonstrated accurate capability, especially with broad participant cohort (ROC-AUC up 0.82). Prospectively applying , synthesized predicted our or non-immunogenic. Ex testing PBMCs healthy participants showed elicited significantly higher responses than non-immunogenic validating Conclusions Our approach, integrating antigen effectively predicts epitopes across different bacterial pathogens. This method enhances selection efficiency, aiding vaccine development immunological research reducing need extensive experimental screening.

Language: Английский

Maintenance and functional regulation of immune memory to COVID-19 vaccines in tissues DOI
Julia Davis‐Porada, Alex George, Nora Lam

et al.

Immunity, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

9
Evolution of SARS-CoV-2 T cell responses as a function of multiple COVID-19 boosters DOI Creative Commons
Ricardo da Silva Antunes,

Vicente Fajardo-Rosas,

Esther Dawen Yu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

SUMMARY The long-term effects of repeated COVID-19 vaccinations on adaptive immunity remain incompletely understood. Here, we conducted a comprehensive three-year longitudinal study examining T cell and antibody responses in 78 vaccinated individuals without reported symptomatic infections. We observed distinct dynamics Spike-specific humoral cellular immune across multiple vaccine doses. While titers incrementally increased stabilized with each booster, rapidly plateaued, maintaining remarkable stability CD4+ CD8+ subsets. Notably, approximately 30% participants showed reactivity to non-Spike antigens, consistent asymptomatic Single-cell RNA sequencing revealed diverse landscape phenotypes, no evidence exhaustion or significant functional impairment. However, qualitative changes were infection, exhibiting unique immunological characteristics, including frequencies Th17-like cells GZMKhi/IFNR Remarkably, this group associated progressive increase regulatory cells, potentially indicating balanced response that may mitigate immunopathology. By regularly stimulating memory, boosters contribute stable enhanced response, which provide better protection against

Language: Английский

Citations

1
Frequency of dengue virus–specific T cells is related to infection outcome in endemic settings DOI Creative Commons
Rosa Isela Gálvez, Amparo Martínez,

E. Alexandar Escarrega

et al.

JCI Insight, Journal Year: 2025, Volume and Issue: 10(4)

Published: Feb. 23, 2025

Dengue is widespread in tropical and subtropical regions globally imposes a considerable disease burden. Annually, dengue virus (DENV) causes up to 400 million infections, of which approximately 25% present with clinical manifestations ranging from mild fatal. Despite its significance as growing public health concern, developing effective DENV vaccines has been challenging. One reason the lack comprehensive understanding influence exerted by prior infections immune responses cross-reactive properties. To investigate this, we collected samples pediatric cohort study dengue-endemic Managua, Nicaragua. We characterized T cell 71 healthy children who had previously experienced 1 or more natural who, within year after sample collection, subsequent infection that was either symptomatic inapparent. Our investigated effect preexisting DENV-specific on outcomes infection. assessed using an activation-induced marker assay. Children only displayed heterogeneous CD4+ CD8+ frequencies. In contrast, 2 showed significantly higher frequencies associated inapparent rather than These findings demonstrate protective role cells against advance efforts identify correlates dengue.

Language: Английский

Citations

0
Discordant Outcomes of SARS-CoV-2 Infection in Household Contacts DOI
Ye‐Ji Lee, Alison Tarke, Tertuliano Alves Pereira Neto

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
PINK1 is a target of T cell responses in Parkinson’s disease DOI Creative Commons
Gregory P. Williams,

T. Michaelis,

João Rodrigues Lima-Júnior

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 12, 2024

Abstract Parkinson’s disease (PD) is associated with autoimmune T cells that recognize the protein alpha-synuclein in a subset of individuals. Multiple neuroantigens are targets autoinflammatory classical central nervous system diseases such as multiple sclerosis (MS). Here, we explored whether additional autoantigenic PD. We generated 15-mer peptide pools spanning several PD-related proteins implicated PD pathology, including GBA, SOD1, PINK1, parkin, OGDH, and LRRK2. Cytokine production (IFNγ, IL-5, IL-10) against these was measured using fluorospot assay PBMCs from patients age-matched healthy controls. This approach identified unique epitopes their HLA restriction mitochondrial-associated regulator mitochondrial stability, an autoantigen targeted by cells. The cell reactivity predominantly found male PD, which may contribute to heterogeneity Identifying characterizing PINK1 other lead antigen-specific diagnostics, progression markers, and/or novel therapeutic strategies for

Language: Английский

Citations

3
Investigating viral and autoimmune T cell responses associated with post-acute sequelae of COVID-19 DOI
Gregory P. Williams, Esther Dawen Yu, K. I. Shapiro

et al.

Human Immunology, Journal Year: 2024, Volume and Issue: 85(3), P. 110770 - 110770

Published: March 2, 2024

Language: Английский

Citations

3
Targets of influenza Human T cell response are mostly conserved in H5N1 DOI Creative Commons
John Sidney, A-Reum Kim, Rory D. de Vries

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Summary Frequent recent spillovers of subtype H5N1 clade 2.3.4.4b highly pathogenic avian influenza (HPAI) virus into poultry and mammals, especially dairy cattle, including several human cases, increased concerns over a possible future pandemic. Here, we performed an analysis epitope data curated in the Immune Epitope Database (IEDB). We found that patterns immunodominance seasonal viruses circulating humans are similar. further conclude significant fraction T cell epitopes is conserved at level associated with cross-reactivity between sequences, experimentally demonstrate extensive most dominant IEDB. Based on these observations, overall similarity neuraminidase (NA) N1 encoded both HPAI H1N1 as well cross-reactive group 1 HA stalk-reactive antibodies, expect degree pre-existing immunity present general population could blunt severity infections.

Language: Английский

Citations

3
Targets of influenza human T-cell response are mostly conserved in H5N1 DOI Creative Commons
John Sidney, A-Reum Kim, Rory D. de Vries

et al.

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

ABSTRACT Frequent recent spillovers of subtype H5N1 clade 2.3.4.4b highly pathogenic avian influenza (HPAI) virus into poultry and mammals, especially dairy cattle, including several human cases, increased concerns over a possible future pandemic. Here, we performed an analysis epitope data curated in the Immune Epitope Database (IEDB). We found that patterns immunodominance seasonal viruses circulating humans are similar. further conclude significant fraction T-cell epitopes is conserved at level associated with cross-reactivity between sequences, experimentally demonstrate extensive most dominant IEDB. Based on these observations, overall similarity neuraminidase (NA) N1 encoded both HPAI H1N1 as well cross-reactive group 1 HA stalk-reactive antibodies, expect degree pre-existing immunity present general population could blunt severity infections. IMPORTANCE Influenza A (IAVs) cause pandemics can result millions deaths. The presently among top pandemic concern, according to WHO National Institute Allergy Infectious Diseases (NIAID). Previous exposure by infection and/or vaccination given IAV or influences immune responses different clade. Analysis CD4 CD8 conservation sequences revealed levels identity conducive T cell cross-reactivity, suggesting memory should, large extent, cross-recognize viruses. This observation was verified testing from cells non-avian their counterparts. Accordingly, should more widespread outbreak occur, hypothesize might be able limit disease severity.

Language: Английский

Citations

3
In-depth characterization of T cell responses with a combined Activation-Induced Marker (AIM) and Intracellular Cytokine Staining (ICS) assay DOI Creative Commons
Ye Ji Lee, Alison Tarke, Alba Grifoni

et al.

Oxford Open Immunology, Journal Year: 2024, Volume and Issue: 5(1)

Published: Jan. 1, 2024

Since T cells are key mediators in the adaptive immune system, evaluating antigen-specific cell responses is pivotal to understanding function. Commonly used methods for measuring include Activation-Induced Marker (AIM) assays and Intracellular Cytokine Staining (ICS). However, combining these approaches has rarely been reported. This study describes a combined AIM + ICS assay effect of collecting supernatant. Peripheral blood mononuclear (PBMCs) from seven healthy donors were stimulated with DMSO (negative control), Epstein-Barr virus (EBV) peptide pools, PHA (positive control). The markers OX40 CD137+ CD4+ CD69 CD107a CD8+ cells. Cytokine-secreting identified as CD40L+ cytokine+ CD69+ or CD107 Half supernatant was collected before adding BFA/Monensin/CD137 antibody solution assess impact on responses. combination had lower background than CD137+, making CD107a+ more sensitive marker markers. Collecting half did not significantly affect Our protocol enables simultaneous assessment activation cytokine release reducing sample volume testing We also show that does interfere detection.

Language: Английский

Citations

2
Frequency of Dengue Virus-Specific T Cells is related to Infection Outcome in Endemic Settings DOI Creative Commons
Rosa Isela Gálvez, Amparo Martínez,

E. Alexandar Escarrega

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 6, 2024

Abstract Dengue is widespread in tropical and subtropical regions globally leads to a considerable burden of disease. Annually, dengue virus (DENV) causes up 400 million infections, which ~25% present with clinical symptoms ranging from mild fatal. Despite its significance as growing public health concern, the development effective DENV vaccines has been highly challenging. One reasons lack comprehensive understanding influence exerted by prior infections immune responses cross-reactive properties. To investigate this, we collected samples pediatric cohort study dengue-endemic Managua, Nicaragua. We characterized T cell group 71 healthy children who had previously experienced one or more natural who, within year after sample collection, subsequent infection that was either symptomatic (n=25) inapparent (n=46, absence disease). Thus, our designed impact pre-existing specific on outcomes infection. assessed using an activation-induced marker assay (AIM). Children only displayed heterogeneous CD4 + CD8 frequencies. In contrast, two showed significantly higher frequencies cells were associated opposed Taken together, these findings demonstrate protective role against constitute advancement toward identifying correlates fever Graphical

Language: Английский

Citations

1