ArticleExperimental biology and medicine (Maywood, N.J.)2022
The dengue virus 4 component of NIAID's tetravalent TV003 vaccine drives its innate immune signature.
Article in Experimental biology and medicine (Maywood, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 6 citations in OpenAlex.
- Parameters Affecting Dengue Virus Replication in Vero Cells.Vaccine: X · 2026Article
- Dengue virus genetic diversity and lineage dynamics in Thailand: implications for surveillance and vaccine implementation.Virology journal · 2026Article
- GM-CSF and M-CSF Driven Differentiation Differentially Regulates Chikungunya Virus Infection and Antiviral Responses in Human Monocyte-Derived Macrophages.bioRxiv : the preprint server for biology · 2026Article
- Impact of Specific Pattern Mutations on Plaque Formation and Attenuation Properties of Dengue Virus Serotype 3.Advances in virology · 2026Article
- Identification of multifunctional T-cell peptide epitopes for the development of DNA vaccines against dengue virus.Human vaccines & immunotherapeutics · 2025Article
- Opportunities and challenges of mRNA technologies in development of dengue virus vaccine.Frontiers in immunology · 2025Review
- Trends and insights in dengue virus research globally: a bibliometric analysis (1995-2023).Journal of translational medicine · 2024Article
- Introduction to the thematic issue: Recognition of women leaders in Science.Experimental biology and medicine (Maywood, N.J.) · 2022Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Annually, roughly 2.5 billion people are at risk for dengue virus (DENV) infection, and the incidence of infection has increased 30-fold since its discovery in the 1900s. At present, there are no globally licensed antiviral treatments or vaccines that protect against all four of the DENV serotypes. The NIAID Live Attenuated Tetravalent Vaccine (LATV) dengue vaccine candidate is composed of variants of three DENV serotypes attenuated by a 30 nucleotide (Δ30) deletion in the 3' untranslated region and a fourth component that is a chimeric virus in which the prM and E genes of DENV-2 replace those of DENV-4 on the rDEN4Δ30 backbone. The vaccine candidate encodes the non-structural proteins of DENV-1, DENV-3, and DENV-4, which could be of critical importance in the presentation of DENV-specific epitopes in a manner that facilitates antigen presentation and confers higher protection. Our findings demonstrate that the attenuation mechanism (Δ30) resulted in decreased viral infectivity and replication for each vaccine virus in monocyte-derived dendritic cells but were able to generate a robust innate immune response. When tested as monovalent viruses, DEN-4Δ30 displayed the most immunogenic profile. In addition, we found that the tetravalent DENV formulation induced a significantly greater innate immune response than the trivalent formulation. We demonstrate that the presence of two components with a DENV-4Δ30 backbone is necessary for the induction of RANTES, CD40, IP-10, and Type I IFN by the tetravalent formulation. Finally, we found that the DEN-4Δ30 backbone in the DENV-2 component of the vaccine enhanced its antigenic properties, as evidenced by enhanced ability to induce IP-10 and IFNα2 in monocyte-derived dendritic cells. In sum, our study shows that the Δ30 and Δ30/Δ31 mutations attenuate the DENV vaccine strains in terms of replication and infectivity while still allowing the induction of a robust innate immune response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.