Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques

Michael K. McCracken; Caitlin H. Kuklis; Chandrika B. Kannadka; David A. Barvir; Mark A. Sanborn; Adam T. Waickman; Hayden C. Siegfried; Kaitlin A. Victor; Kristin L. Hatch; Rafael De La Barrera; Shannon D. Walls; Wiriya Rutvisuttinunt; Jeffrey R. Currier; Heather Friberg; Richard G. Jarman; Gregory D. Gromowski

doi:10.1038/s41541-021-00339-y

npj Vaccines (May 2021)

Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques

Michael K. McCracken,
Caitlin H. Kuklis,
Chandrika B. Kannadka,
David A. Barvir,
Mark A. Sanborn,
Adam T. Waickman,
Hayden C. Siegfried,
Kaitlin A. Victor,
Kristin L. Hatch,
Rafael De La Barrera,
Shannon D. Walls,
Wiriya Rutvisuttinunt,
Jeffrey R. Currier,
Heather Friberg,
Richard G. Jarman,
Gregory D. Gromowski

Affiliations

Michael K. McCracken: Viral Diseases Branch, Walter Reed Army Institute of Research
Caitlin H. Kuklis: Viral Diseases Branch, Walter Reed Army Institute of Research
Chandrika B. Kannadka: Viral Diseases Branch, Walter Reed Army Institute of Research
David A. Barvir: Viral Diseases Branch, Walter Reed Army Institute of Research
Mark A. Sanborn: Viral Diseases Branch, Walter Reed Army Institute of Research
Adam T. Waickman: Viral Diseases Branch, Walter Reed Army Institute of Research
Hayden C. Siegfried: Viral Diseases Branch, Walter Reed Army Institute of Research
Kaitlin A. Victor: Viral Diseases Branch, Walter Reed Army Institute of Research
Kristin L. Hatch: Viral Diseases Branch, Walter Reed Army Institute of Research
Rafael De La Barrera: Pilot Bioproduction Facility, Walter Reed Army Institute of Research
Shannon D. Walls: Viral Diseases Branch, Walter Reed Army Institute of Research
Wiriya Rutvisuttinunt: Viral Diseases Branch, Walter Reed Army Institute of Research
Jeffrey R. Currier: Viral Diseases Branch, Walter Reed Army Institute of Research
Heather Friberg: Viral Diseases Branch, Walter Reed Army Institute of Research
Richard G. Jarman: Viral Diseases Branch, Walter Reed Army Institute of Research
Gregory D. Gromowski: Viral Diseases Branch, Walter Reed Army Institute of Research

DOI: https://doi.org/10.1038/s41541-021-00339-y
Journal volume & issue: Vol. 6, no. 1
pp. 1 – 12

Abstract

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Abstract Antibody-dependent enhancement (ADE) is suspected to influence dengue virus (DENV) infection, but the role ADE plays in vaccination strategies incorporating live attenuated virus components is less clear. Using a heterologous prime-boost strategy in rhesus macaques, we examine the effect of priming with DENV purified inactivated vaccines (PIVs) on a tetravalent live attenuated vaccine (LAV). Sera exhibited low-level neutralizing antibodies (NAb) post PIV priming, yet moderate to high in vitro ADE activity. Following LAV administration, the PIV primed groups exhibited DENV-2 LAV peak viremias up to 1,176-fold higher than the mock primed group, and peak viremia correlated with in vitro ADE. Furthermore, PIV primed groups had more balanced and higher DENV-1–4 NAb seroconversion and titers than the mock primed group following LAV administration. These results have implications for the development of effective DENV vaccine prime-boost strategies and for our understanding of the role played by ADE in modulating DENV replication.

Published in npj Vaccines

ISSN: 2059-0105 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.nature.com/npjvaccines/

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