1. Enhanced dengue vaccine virus replication and neutralizing antibody responses in immune primed rhesus macaques
- Author
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Kristin Hatch, Mark A. Sanborn, Gregory D. Gromowski, Hayden Siegfried, Michael K. McCracken, Shannon D Walls, Caitlin Kuklis, Heather Friberg, Wiriya Rutvisuttinunt, Richard G. Jarman, Rafael De La Barrera, Chandrika B. Kannadka, David A. Barvir, Kaitlin Victor, Jeffrey R. Currier, and Adam T. Waickman
- Subjects
0301 basic medicine ,Live attenuated vaccines ,viruses ,Immunology ,Viremia ,Dengue virus ,medicine.disease_cause ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Seroconversion ,Neutralizing antibody ,RC254-282 ,Dengue vaccine ,Pharmacology ,Inactivated vaccines ,Attenuated vaccine ,biology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,virus diseases ,RC581-607 ,medicine.disease ,Virology ,Vaccination ,030104 developmental biology ,Infectious Diseases ,Viral replication ,biology.protein ,Immunologic diseases. Allergy - 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
- 2021
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