Evidence map›Paper›PMID 42671174›Full record

Trial reportmSphere2026

Evaluation of inactivated and live attenuated, tetravalent dengue vaccine prime-boost strategies in a randomized, open-label, phase I study: implications for understanding immune correlates of protection.

Michael Koren, Simon Pollett, Keisha Akerele, Christine Lee, Kristin Mills, James E Moon, Paul B Keiser, Jack Hutter, Melinda Hamer, Justin M Curley and 8 more

Abstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in mSphere, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Michael KorenWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Simon PollettWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Keisha AkereleWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Christine LeeWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Kristin MillsWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
James E MoonWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Paul B KeiserWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Jack HutterWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Melinda HamerWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Justin M CurleyWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Nathanial K CopelandWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Stephen J ThomasWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Michael K McCrackenWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Jun HangWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Richard G JarmanWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Jeffrey R CurrierWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Heather FribergWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0001-5173-2701
Gregory D GromowskiWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.ORCID 0000-0003-4576-4277

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vaccines that elicit balanced, protective immunity to all four dengue virus (DENV) types are needed to reduce the global burden of dengue disease. Achieving this goal has been a challenge for dengue vaccine developers, particularly when immunizing dengue immunologically naïve individuals. In this randomized, phase I, open-label study of 40 healthy adults, we evaluated a heterologous, tetravalent purified inactivated vaccine (PIV) prime and a tetravalent live attenuated vaccine (LAV) boost. We compared a 0, 90 day PIV/LAV prime-boost schedule to a 0, 180 day schedule. These two PIV/LAV regimens elicited similar, high, and balanced cellular and humoral immune responses to DENV 1-4, although the condensed schedule was associated with more severe adverse events. In a subsequent clinical trial [K. E. Lyke, J. V. Chua, M. Koren, H. Friberg, et al., Lancet Infect Dis 24:896-908, 2024, https://doi.org/10.1016/S1473-3099(24)00100-2], the PIV/LAV vaccinees were challenged with DENV-1 and most were unprotected and experienced more pronounced dengue fever-like illness than unvaccinated controls. These outcomes underscore critical gaps in our understanding of mechanistic correlates of dengue vaccine-mediated protection and disease risk. IMPORTANCE: Dengue vaccine research and development has been complicated by several factors, including an incomplete understanding of immunologic correlates of protection and immune-mediated risk of severe disease. High and balanced immunity elicited by the tetravalent purified inactivated vaccine (PIV)/live attenuated vaccine (LAV) prime-boost vaccine strategy was predicted to provide protection from dengue virus type 1 (DENV-1) challenge in a subsequent clinical study, but vaccinees were unprotected and had an unexpected increase in symptom severity compared to unvaccinated controls. Evidence of exposure to a specific DENV type by viral genome detection (e.g., by quantitative RT-PCR) in acute samples or measurement of post-exposure, type-specific antibody responses (e.g., by serum antibody depletion) are known correlates of protection. However, current methods of measuring type-specific antibody are not ideal for evaluating groups of vaccinees, even in relatively small clinical trials. Newer, high-throughput methods of determining DENV type-specific immune responses and discovery of other correlates of protection are needed to more reliably evaluate dengue vaccine candidates.

Indexed as

DengueDengue VaccinesDengue VirusAdultAntibodies, ViralFemaleHumansImmunity, CellularImmunity, HumoralImmunization, SecondaryMaleVaccinationVaccines, AttenuatedVaccines, InactivatedYoung AdultAntibodies, ViralDengue VaccinesVaccines, AttenuatedVaccines, Inactivatedclinical trialscorrelates of protectiondengue virusimmunizationlive attenuatedphase Ipurified inactivatedvaccines

Identifiers

PMID42671174
PMCPMC13621856

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.