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Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine

  1. Author:
    Odio, Camila D
    Lowman, Kelsey E
    Law, Melissa
    Aogo, Rosemary A
    Hunsberger, Sally
    Wood, Brad J
    Kassin, Michael
    Levy, Elliot
    Callier,Viviane
    Firdous, Saba
    Hasund, Chloe M
    Voirin, Charlie
    Kattappuram, Robbie
    Yek, Christina
    Manning, Jessica
    Durbin, Anna
    Whitehead, Stephen S
    Katzelnick, Leah C

  2. Author Address

    Viral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. camila.odio@nih.gov., Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK., Division of Clinical Research, Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Interventional Radiology and Center for Interventional Oncology, NIH Clinical Center and National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, USA., Department of Pharmacy, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA., International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Phnom Penh, Cambodia., Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Arbovirus Vaccine Research Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Viral Epidemiology and Immunity Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. leah.katzelnick@nih.gov.,
    1. Year: 2023
    2. Date: May 23
    3. Epub Date: 2023 05 23
  2. Journal: BMC infectious diseases
    1. 23
    2. 1
    3. Pages: 345
  4. Type of Article: Article
  5. Article Number: 345
  1. Abstract:

    The four co-circulating and immunologically interactive dengue virus serotypes (DENV1-4) pose a unique challenge to vaccine design because sub-protective immunity can increase the risk of severe dengue disease. Existing dengue vaccines have lower efficacy in DENV seronegative individuals but higher efficacy in DENV exposed individuals. There is an urgent need to identify immunological measures that are strongly associated with protection against viral replication and disease following sequential exposure to distinct serotypes. This is a phase 1 trial wherein healthy adults with neutralizing antibodies to zero (seronegative), one non-DENV3 (heterotypic), or more than one (polytypic) DENV serotype will be vaccinated with the live attenuated DENV3 monovalent vaccine rDEN3Delta30/31-7164. We will examine how pre-vaccine host immunity influences the safety and immunogenicity of DENV3 vaccination in a non-endemic population. We hypothesize that the vaccine will be safe and well tolerated, and all groups will have a significant increase in the DENV1-4 neutralizing antibody geometric mean titer between days 0 and 28. Compared to the seronegative group, the polytypic group will have lower mean peak vaccine viremia, due to protection conferred by prior DENV exposure, while the heterotypic group will have higher mean peak viremia, due to mild enhancement. Secondary and exploratory endpoints include characterizing serological, innate, and adaptive cell responses; evaluating proviral or antiviral contributions of DENV-infected cells; and immunologically profiling the transcriptome, surface proteins, and B and T cell receptor sequences and affinities of single cells in both peripheral blood and draining lymph nodes sampled via serial image-guided fine needle aspiration. This trial will compare the immune responses after primary, secondary, and tertiary DENV exposure in naturally infected humans living in non-endemic areas. By evaluating dengue vaccines in a new population and modeling the induction of cross-serotypic immunity, this work may inform vaccine evaluation and broaden potential target populations. NCT05691530 registered on January 20, 2023. © 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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External Sources

  1. View Full Text
  2. DOI: 10.1186/s12879-023-08299-5
  3. PMID: 37221466
  4. PMCID: PMC10204028
  5. PII : 10.1186/s12879-023-08299-5

Library Notes

  1. Fiscal Year: FY2022-2023
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