4.7 Article

Development of Bacteriophage Virus-Like Particle Vaccines Displaying Conserved Epitopes of Dengue Virus Non-Structural Protein 1

期刊

VACCINES
卷 9, 期 7, 页码 -

出版社

MDPI
DOI: 10.3390/vaccines9070726

关键词

dengue virus; non-structural protein 1; vaccine; bacteriophage; virus-like particle; VLP; immunization; ELISA; epitope

资金

  1. National Institutes of Allergy and Infectious Disease [R21AI148836]
  2. University of New Mexico School of Medicine Research Allocation Committee
  3. National Center for Advancing Translational Science [KL2 TR001448, UL1TR001449]
  4. ASERT Fellowship [K12 GM088021]
  5. Biology of Infectious Disease and Inflammation Fellowship [T32AI007538]
  6. UNM Comprehensive Cancer Center [NCI P30CA118100]

向作者/读者索取更多资源

Dengue virus (DENV) remains a significant global health issue and efforts to engineer epitope-based vaccines targeting the NS1 protein show promising results in mice, eliciting antibodies that bind to recombinant NS1 and DENV-infected cells. This research highlights the potential of epitope-specific vaccines as a promising approach for developing DENV vaccines or therapeutics.
Dengue virus (DENV) is a major global health problem, with over half of the world's population at risk of infection. Despite over 60 years of efforts, no licensed vaccine suitable for population-based immunization against DENV is available. Here, we describe efforts to engineer epitope-based vaccines against DENV non-structural protein 1 (NS1). NS1 is present in DENV-infected cells as well as secreted into the blood of infected individuals. NS1 causes disruption of endothelial cell barriers, resulting in plasma leakage and hemorrhage. Immunizing against NS1 could elicit antibodies that block NS1 function and also target NS1-infected cells for antibody-dependent cell cytotoxicity. We identified highly conserved regions of NS1 from all four DENV serotypes. We generated synthetic peptides to these regions and chemically conjugated them to bacteriophage Q beta virus-like particles (VLPs). Mice were immunized two times with the candidate vaccines and sera were tested for the presence of antibodies that bound to the cognate peptide, recombinant NS1 from all four DENV serotypes, and DENV-2-infected cells. We found that two of the candidate vaccines elicited antibodies that bound to recombinant NS1, and one candidate vaccine elicited antibodies that bound to DENV-infected cells. These results show that an epitope-specific vaccine against conserved regions of NS1 could be a promising approach for DENV vaccines or therapeutics to bind circulating NS1 protein.

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