Frontiers in Immunology (Feb 2024)
Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection
- Desirée Rodrigues Plaça,
- Dennyson Leandro M. Fonseca,
- Alexandre H. C. Marques,
- Shahab Zaki Pour,
- Júlia Nakanishi Usuda,
- Gabriela Crispim Baiocchi,
- Caroline Aliane de Souza Prado,
- Ranieri Coelho Salgado,
- Igor Salerno Filgueiras,
- Paula Paccielli Freire,
- Paula Paccielli Freire,
- Vanderson Rocha,
- Vanderson Rocha,
- Vanderson Rocha,
- Vanderson Rocha,
- Niels Olsen Saraiva Camara,
- Rusan Catar,
- Guido Moll,
- Guido Moll,
- Igor Jurisica,
- Igor Jurisica,
- Igor Jurisica,
- Vera Lúcia Garcia Calich,
- Lasse M. Giil,
- Laura Rivino,
- Laura Rivino,
- Hans D. Ochs,
- Gustavo Cabral-Miranda,
- Lena F. Schimke,
- Lena F. Schimke,
- Lena F. Schimke,
- Otavio Cabral-Marques,
- Otavio Cabral-Marques,
- Otavio Cabral-Marques,
- Otavio Cabral-Marques,
- Otavio Cabral-Marques,
- Otavio Cabral-Marques
Affiliations
- Desirée Rodrigues Plaça
- Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Dennyson Leandro M. Fonseca
- Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, SP, Brazil
- Alexandre H. C. Marques
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Shahab Zaki Pour
- Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- Júlia Nakanishi Usuda
- Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Gabriela Crispim Baiocchi
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Caroline Aliane de Souza Prado
- Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Ranieri Coelho Salgado
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Igor Salerno Filgueiras
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Paula Paccielli Freire
- Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Paula Paccielli Freire
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Vanderson Rocha
- Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology and Cell Therapy, Hospital das Clínicas, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil
- Vanderson Rocha
- Instituto D’Or de Ensino e Pesquisa, São Paulo, Brazil
- Vanderson Rocha
- Fundação Pró-Sangue-Hemocentro de São Paulo, São Paulo, Brazil
- Vanderson Rocha
- Department of Hematology, Churchill Hospital, University of Oxford, Oxford, United Kingdom
- Niels Olsen Saraiva Camara
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Rusan Catar
- Department of Nephrology and Internal Intensive Care Medicine, Charité University Hospital, Berlin, Germany
- Guido Moll
- Department of Nephrology and Internal Intensive Care Medicine, Charité University Hospital, Berlin, Germany
- Guido Moll
- 0Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT) and Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Universitätsmedizin Berlin, Berlin, Germany
- Igor Jurisica
- 1Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON, Canada
- Igor Jurisica
- 2Departments of Medical Biophysics and Computer Science, University of Toronto, Toronto, ON, Canada
- Igor Jurisica
- 3Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
- Vera Lúcia Garcia Calich
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Lasse M. Giil
- 4Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway
- Laura Rivino
- 5School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
- Laura Rivino
- 6Emerging Infectious Diseases, Duke-National University of Singapore (NUS) Medical School, Singapore, Singapore
- Hans D. Ochs
- 7Department of Pediatrics, University of Washington School of Medicine, and Seattle Children’s Research Institute, Seattle, WA, United States
- Gustavo Cabral-Miranda
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Lena F. Schimke
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Lena F. Schimke
- 8Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, Berlin, Germany
- Lena F. Schimke
- 9Network of Immunity in Infection, Malignancy, Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), São Paulo, SP, Brazil
- Otavio Cabral-Marques
- Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Otavio Cabral-Marques
- Interunit Postgraduate Program on Bioinformatics, Institute of Mathematics and Statistics (IME), University of Sao Paulo (USP), Sao Paulo, SP, Brazil
- Otavio Cabral-Marques
- Departament of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Otavio Cabral-Marques
- Instituto D’Or de Ensino e Pesquisa, São Paulo, Brazil
- Otavio Cabral-Marques
- 8Department of Medicine, Division of Molecular Medicine, Laboratory of Medical Investigation 29, University of São Paulo School of Medicine, Berlin, Germany
- Otavio Cabral-Marques
- 9Network of Immunity in Infection, Malignancy, Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), São Paulo, SP, Brazil
- DOI
- https://doi.org/10.3389/fimmu.2024.1282754
- Journal volume & issue
-
Vol. 15
Abstract
IntroductionDengue virus infection is a global health problem lacking specific therapy, requiring an improved understanding of DENV immunity and vaccine responses. Considering the recent emerging of new dengue vaccines, here we performed an integrative systems vaccinology characterization of molecular signatures triggered by the natural DENV infection (NDI) and attenuated dengue virus infection models (DVTs).Methods and resultsWe analyzed 955 samples of transcriptomic datasets of patients with NDI and attenuated dengue virus infection trials (DVT1, DVT2, and DVT3) using a systems vaccinology approach. Differential expression analysis identified 237 common differentially expressed genes (DEGs) between DVTs and NDI. Among them, 28 and 60 DEGs were up or downregulated by dengue vaccination during DVT2 and DVT3, respectively, with 20 DEGs intersecting across all three DVTs. Enriched biological processes of these genes included type I/II interferon signaling, cytokine regulation, apoptosis, and T-cell differentiation. Principal component analysis based on 20 common DEGs (overlapping between DVTs and our NDI validation dataset) distinguished dengue patients by disease severity, particularly in the late acute phase. Machine learning analysis ranked the ten most critical predictors of disease severity in NDI, crucial for the anti-viral immune response. ConclusionThis work provides insights into the NDI and vaccine-induced overlapping immune response and suggests molecular markers (e.g., IFIT5, ISG15, and HERC5) for anti-dengue-specific therapies and effective vaccination development.
Keywords
