Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates

Andrea Marzi, Flora Engelmann, Friederike Feldmann, Kristen Haberthur, W. Lesley Shupert, Douglas Brining, Dana P. Scott, Thomas W. Geisbert, Yoshihiro Kawaoka, Michael G. Katze, Heinz Feldmann, Ilhem Messaoudi

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Abstract

Ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. These viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents. Although not licensed for human use, recombinant vesicular stomatitis virus (rVSV) expressing the filovirus glycoprotein (GP) has been shown to protect macaques from Ebola virus and Marburg virus infections, both prophylactically and postexposure in a homologous challenge setting. However, the immune mechanisms of protection conferred by this vaccine platform remain poorly understood. In this study, we set out to investigate the role of humoral versus cellular immunity in rVSV vaccine-mediated protection against lethal Zaire ebolavirus (ZEBOV) challenge. Groups of cynomolgus macaques weredepleted of CD4+T, CD8+T, or CD20+Bcells beforeand during vaccination with rVSV/ZEBOV-GP. Unfortunately, CD20-depletedanimals generated a robust IgG response. Therefore, an additional group of vaccinated animals were depleted of CD4+ T cells during challenge. All animals were subsequently challenged with a lethal dose of ZEBOV. Animals depleted of CD8+ T cells survived, suggesting a minimal role for CD8+ T cells in vaccine-mediated protection. Depletion of CD4+ T cells during vaccination caused a complete loss of glycoprotein-specific antibodies and abrogated vaccine protection. In contrast, depletion of CD4+ T cells during challenge resulted in survival of the animals, indicating a minimal role for CD4+ T-cell immunityin rVSV-mediated protection. Our results suggest that antibodies playa critical role in rVSV-mediated protection against ZEBOV.

Original languageEnglish (US)
Pages (from-to)1893-1898
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number5
DOIs
StatePublished - Jan 29 2013

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Marzi, A., Engelmann, F., Feldmann, F., Haberthur, K., Shupert, W. L., Brining, D., Scott, D. P., Geisbert, T. W., Kawaoka, Y., Katze, M. G., Feldmann, H., & Messaoudi, I. (2013). Antibodies are necessary for rVSV/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates. Proceedings of the National Academy of Sciences of the United States of America, 110(5), 1893-1898. https://doi.org/10.1073/pnas.1209591110