Route of inoculation and mosquito vector exposure modulate dengue virus replication kinetics and immune responses in rhesus macaques

Authors

Michael K. McCracken, Walter Reed Army Institute of Research
Gregory D. Gromowski, Walter Reed Army Institute of Research
Lindsey S. Garver, Walter Reed Army Institute of Research
Brad A. Goupil, Louisiana State University
Kathryne D. Walker, Walter Reed Army Institute of Research
Heather Friberg, Walter Reed Army Institute of Research
Jeffrey R. Currier, Walter Reed Army Institute of Research
Wiriya Rutvisuttinunt, Walter Reed Army Institute of Research
Kevin L. Hinton, Walter Reed Army Institute of Research
Rebecca C. Christofferson, Louisiana State University
Christopher N. Mores, Louisiana State UniversityFollow
Yannick Vanloubbeeck, GlaxoSmithKline Pharmaceuticals SA/NV
Clarisse Lorin, GlaxoSmithKline Pharmaceuticals SA/NV
Marie Pierre Malice, GlaxoSmithKline Pharmaceuticals SA/NV
Stephen J. Thomas, Walter Reed Army Institute of Research
Richard G. Jarman, Walter Reed Army Institute of Research
David W. Vaughn, GlaxoSmithKline, USA
J. Robert Putnak, Walter Reed Army Institute of Research

Document Type

Journal Article

Publication Date

4-1-2020

Journal

PLoS Neglected Tropical Diseases

Volume

14

Issue

4

DOI

10.1371/journal.pntd.0008191

Abstract

© Public Library of Science. All rights reserved. Dengue virus (DENV) is transmitted by infectious mosquitoes during blood-feeding via saliva containing biologically-active proteins. Here, we examined the effect of varying DENV infection modality in rhesus macaques in order to improve the DENV nonhuman primate (NHP) challenge model. NHPs were exposed to DENV-1 via subcutaneous or intradermal inoculation of virus only, intradermal inoculation of virus and salivary gland extract, or infectious mosquito feeding. The infectious mosquito feeding group exhibited delayed onset of viremia, greater viral loads, and altered clinical and immune responses compared to other groups. After 15 months, NHPs in the subcutaneous and infectious mosquito feeding groups were re-exposed to either DENV-1 or DENV-2. Viral replication and neutralizing antibody following homologous challenge were suggestive of sterilizing immunity, whereas heterologous challenge resulted in productive, yet reduced, DENV-2 replication and boosted neutralizing antibody. These results show that a more transmission-relevant exposure modality resulted in viral replication closer to that observed in humans.

APA Citation

McCracken, M., Gromowski, G., Garver, L., Goupil, B., Walker, K., Friberg, H., Currier, J., Rutvisuttinunt, W., Hinton, K., Christofferson, R., Mores, C., Vanloubbeeck, Y., Lorin, C., Malice, M., Thomas, S., Jarman, R., Vaughn, D., & Putnak, J. (2020). Route of inoculation and mosquito vector exposure modulate dengue virus replication kinetics and immune responses in rhesus macaques. PLoS Neglected Tropical Diseases, 14 (4). http://dx.doi.org/10.1371/journal.pntd.0008191