Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants

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Teixeira, Franciane Mouradian Emidio ; Oliveira, Luana de Mendonca ; Branco, Anna Claudia Calvielli Castelo ; Alberca, Ricardo Wesley ; de Sousa, Emanuella Sarmento Alho ; Leite, Bruno Henrique de Sousa ; Adan, Wenny Camilla dos Santos ; Duarte, Alberto Jose da Silva ; Lins, Roberto Dias ; Sato, Maria Notomi ; Viana, Isabelle Freire Tabosa

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 15, p. 12-pg., 2024-01-19.

Abstract

Zika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_Delta STP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_Delta STP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-Delta STP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_Delta STP+Alum protected adult mice upon viral challenge. Collectively, the ZK_Delta STP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies. (AU)

• FAPESP's process: 18/18230-6 - Evaluation of the efficacy of the Zika Virus chimeric DNA vaccine and the lysosomal-associated membrane protein in mice
• Grantee: Franciane Mouradian Emidio Teixeira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/25119-7 - Maternal-fetal interface: immunopathogenesis and vaccinal intervention in viral infections
• Grantee: Maria Notomi Sato
• Support Opportunities: Research Projects - Thematic Grants