Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections
Orthoflaviviruses, a group of arthropod-borne viruses, represent a significant global health threat, with hundreds of millions of infections each year, often leading to severe clinical outcomes. This Review elucidates the complexities of immune imprinting, also known as original antigenic sin (OAS),...
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| Format: | Article |
| Language: | English |
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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.2025.1560851/full |
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| author | Gielenny M. Salem Fan-Chi Chen James J. Cai Day-Yu Chao Day-Yu Chao Day-Yu Chao |
| author_facet | Gielenny M. Salem Fan-Chi Chen James J. Cai Day-Yu Chao Day-Yu Chao Day-Yu Chao |
| author_sort | Gielenny M. Salem |
| collection | DOAJ |
| description | Orthoflaviviruses, a group of arthropod-borne viruses, represent a significant global health threat, with hundreds of millions of infections each year, often leading to severe clinical outcomes. This Review elucidates the complexities of immune imprinting, also known as original antigenic sin (OAS), and its influence on immune responses to repeated, heterologous orthoflavivirus infections. We examine how initial exposure to a virus can shape subsequent immune responses, potentially resulting in sub-optimal binding of pre-existing antibodies to related but distinct viruses. Although OAS is often linked with adverse outcomes, such as enhanced disease severity in dengue due to antibody-dependent enhancement, we re-introduce the concept of “antigenic seniority,” which highlights the potential advantages of prior exposures by promoting cross-protection against related variants. This perspective underscores the dual nature of immune imprinting and its implications for vaccine development and therapeutic strategies against orthoflavivirus infections. By exploring the delicate balance between protective and maladaptive immune responses, we emphasize critical considerations for developing effective vaccines and interventions in the context of evolving viral threats. |
| format | Article |
| id | doaj-art-ec4e2ed0a8bb4fdf9aff310861ccbcba |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-ec4e2ed0a8bb4fdf9aff310861ccbcba2025-08-20T03:27:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15608511560851Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infectionsGielenny M. Salem0Fan-Chi Chen1James J. Cai2Day-Yu Chao3Day-Yu Chao4Day-Yu Chao5Infection Biology Program, Global Center for Pathogen Research and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United StatesDoctoral Program in Microbial Genomics, National Chung Hsing University and Academia Sinica, Taichung City, TaiwanDepartment of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, United StatesDoctoral Program in Microbial Genomics, National Chung Hsing University and Academia Sinica, Taichung City, TaiwanGraduate Institute of Microbiology and Public Health, College of Veterinary Medicine, National Chung Hsing University, Taichung City, TaiwanDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City, TaiwanOrthoflaviviruses, a group of arthropod-borne viruses, represent a significant global health threat, with hundreds of millions of infections each year, often leading to severe clinical outcomes. This Review elucidates the complexities of immune imprinting, also known as original antigenic sin (OAS), and its influence on immune responses to repeated, heterologous orthoflavivirus infections. We examine how initial exposure to a virus can shape subsequent immune responses, potentially resulting in sub-optimal binding of pre-existing antibodies to related but distinct viruses. Although OAS is often linked with adverse outcomes, such as enhanced disease severity in dengue due to antibody-dependent enhancement, we re-introduce the concept of “antigenic seniority,” which highlights the potential advantages of prior exposures by promoting cross-protection against related variants. This perspective underscores the dual nature of immune imprinting and its implications for vaccine development and therapeutic strategies against orthoflavivirus infections. By exploring the delicate balance between protective and maladaptive immune responses, we emphasize critical considerations for developing effective vaccines and interventions in the context of evolving viral threats.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1560851/fullorthoflavivirusesimmune imprintingoriginal antigenic sin (OAS)antibody-dependent enhancement (ADE)antigenic seniority |
| spellingShingle | Gielenny M. Salem Fan-Chi Chen James J. Cai Day-Yu Chao Day-Yu Chao Day-Yu Chao Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections Frontiers in Immunology orthoflaviviruses immune imprinting original antigenic sin (OAS) antibody-dependent enhancement (ADE) antigenic seniority |
| title | Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections |
| title_full | Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections |
| title_fullStr | Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections |
| title_full_unstemmed | Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections |
| title_short | Factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections |
| title_sort | factors determining the outcomes of immune imprinting after repeated orthoflavivirus infections |
| topic | orthoflaviviruses immune imprinting original antigenic sin (OAS) antibody-dependent enhancement (ADE) antigenic seniority |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1560851/full |
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