Immunological signatures unveiled by integrative systems vaccinology characterization of dengue vaccination trials and natural infection

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Placa, Desiree Rodrigues ; Fonseca, Dennyson Leandro M. ; Marques, Alexandre H. C. ; Zaki Pour, Shahab ; Usuda, Julia Nakanishi ; Baiocchi, Gabriela Crispim ; Prado, Caroline Aliane de Souza ; Salgado, Ranieri Coelho ; Filgueiras, Igor Salerno ; Freire, Paula Paccielli ; Rocha, Vanderson ; Camara, Niels Olsen Saraiva ; Catar, Rusan ; Moll, Guido ; Jurisica, Igor ; Calich, Vera Lucia Garcia ; Giil, Lasse M. ; Rivino, Laura ; Ochs, Hans D. ; Cabral-Miranda, Gustavo ; Schimke, Lena F. ; Cabral-Marques, Otavio

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 15, p. 17-pg., 2024-02-20.

Abstract

Introduction Dengue 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 results We 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.Conclusion This 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. (AU)

• FAPESP's process: 20/16246-2 - Holistic characterization of T cell exhaustion in patients with Zika
• Grantee: Dennyson Leandro Mathias da Fonseca
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/07069-0 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
• Grantee: Otávio Cabral Marques
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/09146-1 - Systemic and integrative analysis of molecular mechanisms associated with immunoregulation in patients with COVID-19
• Grantee: Paula Paccielli Freire-Barguil
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/01688-0 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 18/18886-9 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/07972-1 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
• Grantee: Gabriela Crispim Baiocchi
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/11710-2 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with Dengue
• Grantee: Desirée Rodrigues Plaça
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 21/03675-5 - Analysis of the network of IFN-associated molecules in Dengue fever patients
• Grantee: Júlia Nakanishi Usuda
• Support Opportunities: Scholarships in Brazil - Scientific Initiation