Trial reportThe Journal of clinical investigation2021
Dengue vaccine breakthrough infections reveal properties of neutralizing antibodies linked to protection.
Trial report in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Dengue vaccines: The role of a correlate of protection in evaluating vaccine safety and risk.Vaccine · 2026Article
- A secretion-deficient DENV1 DNA vaccine induces durable immunity and confers protection against DENV2.Zoological research · 2026Article
- Safety of a tetravalent live dengue virus vaccine in children responding to one serotype only.JCI insight · 2026Article
- Enhancing, controlling, and sterilizing dengue immunity and the development of broadly protective responses.medRxiv : the preprint server for health sciences · 2026Article
- Protective envelope dimer epitope-like antibodies are elicited against dengue virus in children after infection and vaccination.Science translational medicine · 2025Article
- Review
- Dengue virus IgG and neutralizing antibody titers measured with standard and mature viruses are protective.Nature communications · 2025Article
- BCG cell wall skeleton augments the immunogenicity of dengue nanoparticle vaccines by promoting dendritic cell activation.PloS one · 2025Article
- Dengue severity by serotype and immune status in 19 years of pediatric clinical studies in Nicaragua.PLoS neglected tropical diseases · 2025Article
- Animal Models, Therapeutics, and Vaccine Approaches to Emerging and Re-Emerging Flaviviruses.Viruses · 2024Review
- Predicting the infecting dengue serotype from antibody titre data using machine learning.PLoS computational biology · 2024Article
- Improving precision of vaccine efficacy evaluation using immune correlate data in time-to-event models.NPJ vaccines · 2024Article
- Preclinical Evaluation of Novel Sterically Optimized VLP-Based Vaccines against All Four DENV Serotypes.Vaccines · 2024Article
- Dengue.Lancet (London, England) · 2024Review
- Heterologous prime-boost immunization induces protection against dengue virus infection in cynomolgus macaques.Journal of virology · 2023Article
- Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination.Cell host & microbe · 2023Article
- A Prototype-Pathogen Approach for the Development of Flavivirus Countermeasures.The Journal of infectious diseases · 2023Review
- Blockade-of-Binding Activities toward Envelope-Associated, Type-Specific Epitopes as a Correlative Marker for Dengue Virus-Neutralizing Antibody.Microbiology spectrum · 2023Article
- Resurgence of Dengue Virus Serotype 4 in Malaysia: A Comprehensive Clinicodemographic and Genomic Analysis.Tropical medicine and infectious disease · 2023Article
- Novel approaches for the rapid development of rationally designed arbovirus vaccines.One health (Amsterdam, Netherlands) · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The 4 serotypes of dengue virus (DENV1-4) are mosquito-borne flaviviruses that infect humans. Live attenuated tetravalent DENV vaccines are at different phases of clinical testing. DENV vaccine developers have relied on neutralizing antibodies (NAbs) as a correlate of protection. A leading tetravalent vaccine (Dengvaxia) stimulated NAbs to the 4 DENV serotypes, yet overall vaccine efficacy was low in children who were DENV seronegative at baseline before vaccination. We compared the properties of (a) NAbs induced by WT DENV1 or DENV3 infections, which are strongly correlated with protection from repeat infections, and (b) NAbs induced by Dengvaxia in individuals who subsequently experienced DENV1 or DENV3 breakthrough infections. WT infections induced NAbs that recognized epitopes unique (type specific) to each serotype, whereas the vaccine stimulated qualitatively different NAbs that recognized epitopes conserved (crossreactive) between serotypes. Our results indicate that, among children who were DENV-seronegative at baseline, unbalanced replication of the DENV type 4 vaccine component in the tetravalent vaccine stimulates Abs capable of crossneutralizing DENV1 and DENV3 in vitro, but not protecting in vivo. In DENV-seronegative individuals who are vaccinated, we propose that type-specific NAbs are a better correlate of protection than total levels of NAbs.
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Registered trials
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.