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

Understanding the impact of adult pertussis and current approaches to vaccination: A narrative review and expert panel recommendations DOI Creative Commons
Péter Kardos, Jaime Correia de Sousa, Ulrich Heininger

et al.

Human Vaccines & Immunotherapeutics, Journal Year: 2024, Volume and Issue: 20(1)

Published: April 2, 2024

Pertussis has several notable consequences, causing economic burden, increased strain on healthcare facilities, and reductions in quality of life. Recent years have seen a trend toward an increase pertussis cases affecting older children adults. To boost immunity, protect vulnerable populations, enduring approach to vaccination been proposed, but gaps remain the evidence surrounding adult that are needed inform such policy. Gaps include: true incidence its complications adults; regional variations disease recognition reporting; severe disease, hospitalizations, deaths Better data efficacy/effectiveness adults, duration protection, factors leading poor vaccine uptake needed. Addressing critical will help highlight important areas unmet need justify importance professionals, policymakers, payers.

Language: Английский

Citations

9
Th1 polarization in Bordetella pertussis vaccine responses is maintained through a positive feedback loop DOI Creative Commons
Lisa Willemsen,

Jiyeun Lee,

Pramod Shinde

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 1, 2025

Language: Английский

Citations

1
The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses DOI Creative Commons
Ricardo da Silva Antunes, Daniela Weiskopf, John Sidney

et al.

Current Protocols, Journal Year: 2023, Volume and Issue: 3(11)

Published: Nov. 1, 2023

Abstract Epitopes recognized by T cells are a collection of short peptide fragments derived from specific antigens or proteins. Immunological research to study cell responses is hindered the extreme degree heterogeneity epitope targets, which usually multiple antigens; within given antigen, hundreds different epitopes can be recognized, differing one individual next because recognition restricted epitopes’ ability bind MHC molecules, extremely polymorphic in individuals. Testing large pools encompassing peptides technically challenging logistical considerations regarding solvent‐induced toxicity. To address this issue, we developed MegaPool (MP) approach based on sequential lyophilization numbers that used variety assays measure responses, including ELISPOT, intracellular cytokine staining, and activation‐induced marker assays, has been validated infectious diseases, allergies, autoimmunity. Here, describe procedures for generating testing MPs, starting with synthesis lyophilization, as well step‐by‐step guide recommendations their handling experimental usage. Overall, MP powerful strategy studying understanding immune system's role health disease. © 2023 The Authors. Current Protocols published Wiley Periodicals LLC. Basic Protocol 1 : Generation (“MegaPools”) 2 quantitation antigen‐specific

Language: Английский

Citations

15
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
Bordetella spp. block eosinophil recruitment to suppress the generation of early mucosal protection DOI Creative Commons

Nicholas J. First,

Katelyn M. Parrish, Amparo Martínez

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(11), P. 113294 - 113294

Published: Oct. 25, 2023

Bordetella spp. are respiratory pathogens equipped with immune evasion mechanisms. We previously characterized a bronchiseptica mutant (RB50ΔbtrS) that fails to suppress host responses, leading rapid clearance and long-lasting immunity against reinfection. This work revealed eosinophils as an exclusive requirement for RB50ΔbtrS clearance. also show promotes eosinophil-mediated B/T cell recruitment inducible bronchus-associated lymphoid tissue (iBALT) formation, being present throughout iBALT Th17 immunoglobulin A (IgA) responses. Finally, we provide evidence XCL1 is critical formation but not maintenance, proposing novel role facilitators of adaptive B. bronchiseptica. incapable suppressing eosinophil effector functions illuminates active, bacterial targeting achieve successful persistence Overall, our discoveries contribute understanding cellular mechanisms use in future vaccines therapies extension other mucosal pathogens.

Language: Английский

Citations

5
The identification and characterization of novel and improved antigens for next-generation pertussis vaccines DOI Creative Commons
Gage M. Pyles

Published: Jan. 1, 2024

Whooping cough, or pertussis, is a highly infectious respiratory disease caused by infection with the Gram-negative bacterial pathogen Bordetella pertussis. Pertussis affects all age groups and populations; however, it most severe in infants who are too young to receive vaccinations remains global health concern more than­­­­ 200,000 cases reported globally 2023. Vaccines against pertussis have been available United States since 1940's development widespread use of whole cell vaccines. Following their introduction, incidence was controlled limited fewer than 5,000 per year. Despite demonstrated efficacy, vaccines were immunogenic variable nature often led worrisome, side effects. Due this, replaced lesser reactogenic acellular 1990's, which still this day industrialized countries. After introduction vaccines, there has an increase several noteworthy outbreaks, such as U.S. outbreak 2012 resulted over 50,000 20 deaths, 2024 Czech Republic experienced its highest 1960s. This reemergence calls for next-generation address overcome pitfalls current There many hypotheses why triggered resurgence, including evolution response selective pressure on vaccine antigens, increased rates reporting, well short-lived duration immunity that follows vaccination. The overall objective worked covered thesis additional pitfall being breadth antigen coverage lack thereof functional immune responses can promote clearance. In these studies, we employed murine model vaccination B. challenge novel redesigned antigens assessed capability invoke robust humoral subsequently protect At onset work, identified proteins contained mice when formulated peptide-based conjugate Although immunogenic, peptides insufficient elicit protection mice. Next, characterized immunogenicity protective efficacy derived from iron acquisition surface receptors expressed previously found be upregulated upon infection. Similarly, however they failed confer either alone combination subprotective dose DTaP. Finally, instead characterizing sought redesign known filamentous hemagglutinin. Toward goal, designed truncated based mature C-terminal domain hemagglutinin fused virus-like particles. conferred significant evaluated strain lacking toxin. Overall, work redesigned, promise could included next generation Additionally, sheds light complexity preclinical lays groundwork future exploration other platforms.

Language: Английский

Citations

1
Adaptive immune response to bordetella pertussis during vaccination and infection: emerging perspectives and unanswered questions DOI Creative Commons
A-Reum Kim, Alessandro Sette, Ricardo da Silva Antunes

et al.

Expert Review of Vaccines, Journal Year: 2024, Volume and Issue: 23(1), P. 705 - 714

Published: July 22, 2024

Whooping cough, also known as pertussis, remains a significant challenge vaccine-preventable disease worldwide. Since the switch from whole-cell Pertussis (wP) vaccine to acellular (aP), cases of whooping cough have increased in countries using aP vaccine. Understanding immune system's response pertussis vaccines and infection is crucial for improving current efficacy.

Language: Английский

Citations

0
Th1 polarization inBordetella pertussisvaccine responses is maintained through a positive feedback loop DOI Creative Commons
Lisa Willemsen,

Jiyeun Lee,

Pramod Shinde

et al.

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

Published: Aug. 7, 2024

Outbreaks of

Language: Английский

Citations

0
Prevalence of Bordetella pertussis among children aged 4 years and above presenting with acute respiratory tract infection: a cross-sectional study DOI

Ainun Nadzurah Binti Md Bahar,

Anis Najwa Muhamad, Cindy Shuan Ju Teh

et al.

Pathogens and Global Health, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 5

Published: Sept. 8, 2024

In Malaysia, pertussis in children beyond infancy is underreported. This study aimed to determine the prevalence of

Language: Английский

Citations

0
Identification of immunogenic and cross-reactive chikungunya virus-specific CD4+ T cell epitopes in chronic chikungunya viral arthritic disease in humans DOI Creative Commons
Rimjhim Agarwal,

Calvin Ha,

Fernanda H. Cortes

et al.

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

Published: Oct. 25, 2024

ABSTRACT Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes acute febrile illness that can progress into chronic chikungunya disease (CHIKVD) marked by persistent debilitating arthralgia. At present, the exact cause of CHIKVD is not understood, and in humans, targets CD4 + T cells CHIKV are currently unknown. Here, stimulating peripheral blood mononuclear (PBMCs) collected from patients suffering with peptides spanning entire genome, we provide comprehensive landscape cell epitopes. We identified 123 novel epitopes three immunodominant regions E1, nsP1 CP proteins. The immunodominance these was mapped to optimal epitopes, characterized capacity bind many common HLA class II allelic variants. In addition, designed validated new CHIKV-specific epitope megapool, both structural non-structural proteins, which be useful tool study responses small volumes, typically available pediatric or clinical samples. Finally, silico assessment conservation proteome diverse set alphaviruses, defined conserved across arthritogenic encephalitic viruses. Overall, our work first identify expanding role pathogenesis mapping alphaviruses for vaccine design.

Language: Английский

Citations

0