• Heterologous prime-boost immunization induces protection against dengue virus infection in cynomolgus macaques

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Document Title

Heterologous prime-boost immunization induces protection against dengue virus infection in cynomolgus macaques

Author

Keelapang P. Ketloy C. Puttikhunt C. Sriburi R. Prompetchara E. Sae-Lim M. Siridechadilok B. Duangchinda T. Noisakran S. Charoensri N. Suriyaphol P. Suparattanagool P. Utaipat U. Masrinoul P. Avirutnan P. Mongkolsapaya J. Screaton G. Auewarakul P. Malaivijitnond S. Yoksan S. Malasit P. Ruxrungtham K. Pulmanausahakul R. Sittisombut N.

Affiliations

Department of Microbiology Faculty of Medicine Chiang Mai University Chiang Mai Thailand; Center of Excellence in Vaccine Research and Development Faculty of Medicine Chulalongkorn University Bangkok Thailand; Department of Laboratory Medicine Faculty of Medicine Chulalongkorn University Bangkok Thailand; Molecular Biology of Dengue and Flaviviruses Research Team Medical Molecular Biotechnology Research Group National Center for Genetic Engineering and Biotechnology National Science and Technology Development Agency Pathumthani Thailand; Division of Dengue Hemorrhagic Fever Research Siriraj Center of Research Excellence in Dengue and Emerging Pathogens Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand; Frontier Biodesign and Bioengineering Research Team National Center for Genetic Engineering and Biotechnology Pathumthani Thailand; Center for Research and Development of Medical Diagnostic Laboratories Faculty of Associated Medical Sciences Khon Kaen University Khon Kaen Thailand; Siriraj Informatics and Data Innovation Center Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand; Clinical Epidemiology Unit Faculty of Medicine Khon Kaen University Khon Kaen Thailand; Research Institute for Health Sciences Chiang Mai University Chiang Mai Thailand; Center for Vaccine Development Institute of Molecular Biosciences Mahidol University at Salaya Nakhon Pathom Thailand; Wellcome Centre for Human Genetics Nuffield Department of Medicine University of Oxford Oxford United Kingdom; Department of Microbiology Faculty of Medicine Siriraj Hospital Mahidol University Bangkok Thailand; National Primate Research Center of Thailand Chulalongkorn University Bangkok Thailand; Princess Srisavangavadhana College of Medicine Chulabhorn Royal Academy Bangkok Thailand

Type

Article

Source Title

Journal of Virology

ISSN

0022538X

Year

2023

Volume

97

Issue

11-�.�.

Open Access

All Open Access Hybrid Gold Green

Publisher

American Society for Microbiology

DOI

10.1128/jvi.00963-23

Abstract

Currently licensed dengue vaccines do not induce long-term protection in children without prior dengue virus exposure. A better understanding of the mechanism by which the immune system prevents dengue virus infection is urgently needed to improve vaccine efficacy. In this study the induction of protective antibody responses against dengue virus infection was tested in a non-human primate model using the heterologous prime-boost vaccination approach. Groups of cynomolgus macaques were immunized with a priming dose of attenuated dengue viruses and followed by two booster doses of virus-like particles in four monovalent arms or in the tetravalent arm (prM + E)-expressing plasmids. At 1 month post-immunization all macaques had elevated levels of neutralizing antibodies and live viral challenges revealed an overall protective efficacy of 91% (40/44 macaques protected) against infection with clinical isolates. Breakthrough infections occurred in macaques with distinctive antibody profiles at the time of challenge: two macaques had the lowest neutralizing antibodies against the respective DENV-1 and -4 challenge strains among the respective groups whereas two other DENV-4-infected macaques exhibited high levels of neutralizing and virus-binding antibodies. The ratio of antibodies recognizing a DENV-4-specific epitope and those that bound viral particles was at the lowest levels in the latter DENV-4-infected macaques indicating an underrepresentation of antibodies targeting the serotype-specific epitope. Protection among macaques challenged with DENV-2 or -3 coincided with vigorous EDIII-binding antibody responses induced by booster immunization. A combination of attenuated viruses for priming and non-infectious particle-based antigens for boosting may be a more effective means of preventing dengue. Copyright ? 2023 Keelapang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

License

CC BY

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