PepSeq as a highly multiplexed platform for melioidosis antigen discovery and vaccine development
IntroductionVaccination aims to prevent or mitigate disease by priming the immune system prior to infection. While historical vaccine development relied mostly on trial-and-error, modern approaches have become more directed. By leveraging our growing understanding of pathogen biology and immune corr...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1605758/full |
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| author | Evan A. Elko Charles H. D. Williamson Heather R. Green Marcellene A. Gates-Hollingsworth Georgia A. Nelson Sujata G. Pandit Heather L. Mead Christopher Allender Celeste Woerle Mark Mayo Bart J. Currie Bart J. Currie David P. AuCoin John A. Altin Paul Keim Paul Keim Paul Keim Erik W. Settles Erik W. Settles Jason T. Ladner Jason T. Ladner |
| author_facet | Evan A. Elko Charles H. D. Williamson Heather R. Green Marcellene A. Gates-Hollingsworth Georgia A. Nelson Sujata G. Pandit Heather L. Mead Christopher Allender Celeste Woerle Mark Mayo Bart J. Currie Bart J. Currie David P. AuCoin John A. Altin Paul Keim Paul Keim Paul Keim Erik W. Settles Erik W. Settles Jason T. Ladner Jason T. Ladner |
| author_sort | Evan A. Elko |
| collection | DOAJ |
| description | IntroductionVaccination aims to prevent or mitigate disease by priming the immune system prior to infection. While historical vaccine development relied mostly on trial-and-error, modern approaches have become more directed. By leveraging our growing understanding of pathogen biology and immune correlates of protection, we can design vaccines in ways that promote protective responses. However, the complexity of many pathogens (e.g., bacteria and fungi), as well as our immune responses against them, continue to present important challenges for vaccine development.AimHere, we demonstrate the utility of the PepSeq platform for highly multiplexed serology to both broadly and finely characterize antibody responses against complex pathogens, using the bacterium, Burkholderia pseudomallei, as a case study.MethodsWe designed and synthesized three diverse pools of DNA-barcoded peptides (i.e., PepSeq libraries) and used them to characterize antibodies against a variety of B. pseudomallei proteins.ResultsEpitope-resolved antibody binding profiles were generated for 85 individuals with culture-confirmed melioidosis, 89 US blood bank controls, and 6 monoclonal antibodies. Using these data, we identify novel B cell antigens/epitopes and finely characterize the epitopes of three monoclonal antibodies against the B. pseudomallei GroEL protein.ConclusionHighly multiplexed serology platforms, like PepSeq, enable more comprehensive characterization of antibodies, both polyclonal and monoclonal, which can aid in the development of vaccines, diagnostics and therapeutics, even for pathogens with large, complex genomes. |
| format | Article |
| id | doaj-art-ee9afcd5c08b48eeab61c5965b92f0fb |
| institution | Matheson Library |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-ee9afcd5c08b48eeab61c5965b92f0fb2025-07-03T05:26:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16057581605758PepSeq as a highly multiplexed platform for melioidosis antigen discovery and vaccine developmentEvan A. Elko0Charles H. D. Williamson1Heather R. Green2Marcellene A. Gates-Hollingsworth3Georgia A. Nelson4Sujata G. Pandit5Heather L. Mead6Christopher Allender7Celeste Woerle8Mark Mayo9Bart J. Currie10Bart J. Currie11David P. AuCoin12John A. Altin13Paul Keim14Paul Keim15Paul Keim16Erik W. Settles17Erik W. Settles18Jason T. Ladner19Jason T. Ladner20The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United StatesThe Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United StatesDepartment of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, United StatesDepartment of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, United StatesThe Translational Genomics Research Institute, Flagstaff, AZ, United StatesDepartment of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, United StatesThe Translational Genomics Research Institute, Flagstaff, AZ, United StatesThe Translational Genomics Research Institute, Flagstaff, AZ, United StatesGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT, AustraliaInfectious Diseases Department and Northern Territory Medical Program, Royal Darwin Hospital, Darwin, NT, AustraliaDepartment of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, United StatesThe Translational Genomics Research Institute, Flagstaff, AZ, United StatesThe Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United StatesThe Translational Genomics Research Institute, Flagstaff, AZ, United StatesDepartment of Biological Sciences, Northern Arizona University, Flagstaff, AZ, United StatesThe Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United StatesDepartment of Biological Sciences, Northern Arizona University, Flagstaff, AZ, United StatesThe Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United StatesDepartment of Biological Sciences, Northern Arizona University, Flagstaff, AZ, United StatesIntroductionVaccination aims to prevent or mitigate disease by priming the immune system prior to infection. While historical vaccine development relied mostly on trial-and-error, modern approaches have become more directed. By leveraging our growing understanding of pathogen biology and immune correlates of protection, we can design vaccines in ways that promote protective responses. However, the complexity of many pathogens (e.g., bacteria and fungi), as well as our immune responses against them, continue to present important challenges for vaccine development.AimHere, we demonstrate the utility of the PepSeq platform for highly multiplexed serology to both broadly and finely characterize antibody responses against complex pathogens, using the bacterium, Burkholderia pseudomallei, as a case study.MethodsWe designed and synthesized three diverse pools of DNA-barcoded peptides (i.e., PepSeq libraries) and used them to characterize antibodies against a variety of B. pseudomallei proteins.ResultsEpitope-resolved antibody binding profiles were generated for 85 individuals with culture-confirmed melioidosis, 89 US blood bank controls, and 6 monoclonal antibodies. Using these data, we identify novel B cell antigens/epitopes and finely characterize the epitopes of three monoclonal antibodies against the B. pseudomallei GroEL protein.ConclusionHighly multiplexed serology platforms, like PepSeq, enable more comprehensive characterization of antibodies, both polyclonal and monoclonal, which can aid in the development of vaccines, diagnostics and therapeutics, even for pathogens with large, complex genomes.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1605758/fullPepSeqhighly multiplexed serologymelioidosisBurkholderia pseudomalleivaccineepitope |
| spellingShingle | Evan A. Elko Charles H. D. Williamson Heather R. Green Marcellene A. Gates-Hollingsworth Georgia A. Nelson Sujata G. Pandit Heather L. Mead Christopher Allender Celeste Woerle Mark Mayo Bart J. Currie Bart J. Currie David P. AuCoin John A. Altin Paul Keim Paul Keim Paul Keim Erik W. Settles Erik W. Settles Jason T. Ladner Jason T. Ladner PepSeq as a highly multiplexed platform for melioidosis antigen discovery and vaccine development Frontiers in Immunology PepSeq highly multiplexed serology melioidosis Burkholderia pseudomallei vaccine epitope |
| title | PepSeq as a highly multiplexed platform for melioidosis antigen discovery and vaccine development |
| title_full | PepSeq as a highly multiplexed platform for melioidosis antigen discovery and vaccine development |
| title_fullStr | PepSeq as a highly multiplexed platform for melioidosis antigen discovery and vaccine development |
| title_full_unstemmed | PepSeq as a highly multiplexed platform for melioidosis antigen discovery and vaccine development |
| title_short | PepSeq as a highly multiplexed platform for melioidosis antigen discovery and vaccine development |
| title_sort | pepseq as a highly multiplexed platform for melioidosis antigen discovery and vaccine development |
| topic | PepSeq highly multiplexed serology melioidosis Burkholderia pseudomallei vaccine epitope |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1605758/full |
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