Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection

dc.contributor.authorde Swart, Rik L.
dc.contributor.authorde Vries, Rory D.
dc.contributor.authorRennick, Linda J.
dc.contributor.authorvan Amerongen, Geert
dc.contributor.authorMcQuaid, Stephen
dc.contributor.authorVerburgh, R. Joyce
dc.contributor.authorYuksel, Selma
dc.contributor.authorde Jong, Alwin
dc.contributor.authorLemon, Ken
dc.contributor.authorNguyen, D. Tien
dc.contributor.authorLudlow, Martin
dc.contributor.authorOsterhaus, Albert D.M.E.
dc.contributor.authorDuprex, W. Paul
dc.descriptionPublication history: Accepted - 8 June 2017; Published online - 1 August 2017.en_US
dc.description.abstractNeedle-free measles virus vaccination by aerosol inhalation has many potential benefits. The current standard route of vaccination is subcutaneous injection, whereas measles virus is an airborne pathogen. However, the target cells that support replication of liveattenuated measles virus vaccines in the respiratory tract are largely unknown. The aims of this study were to assess the in vivo tropism of live-attenuated measles virus and determine whether respiratory measles virus vaccination should target the upper or lower respiratory tract. Four groups of twelve cynomolgus macaques were immunized with 104 TCID50 of recombinant measles virus vaccine strain Edmonston-Zagreb expressing enhanced green fluorescent protein. The vaccine virus was grown in MRC-5 cells and formulated with identical stabilizers and excipients as used in the commercial MVEZ vaccine produced by the Serum Institute of India. Animals were immunized by hypodermic injection, intra-tracheal inoculation, intra-nasal instillation, or aerosol inhalation. In each group six animals were euthanized at early time points post-vaccination, whereas the other six were followed for 14 months to assess immunogenicity and protection from challenge infection with wild-type measles virus. At early time-points, enhanced green fluorescent protein-positive measles virus-infected cells were detected locally in the muscle, nasal tissues, lungs, and draining lymph nodes. Systemic vaccine virus replication and viremia were virtually absent. Infected macrophages, dendritic cells and tissueresident lymphocytes predominated. Exclusive delivery of vaccine virus to the lower respiratory tract resulted in highest immunogenicity and protection. This study sheds light on the tropism of a live-attenuated measles virus vaccine and identifies the alveolar spaces as the optimal site for respiratory delivery of measles virus vaccine.en_US
dc.description.sponsorshipThis study was funded by the Foundation for the National Institutes of Health, through the Bill and Melinda Gates Foundation Grand Challenges in Global Health initiative (grant number: DUPREX09GCGH0).en_US
dc.identifier.citationde Swart, R. L., de Vries, R. D., Rennick, L. J., van Amerongen, G., McQuaid, S., Verburgh, R. J., Yüksel, S., de Jong, A., Lemon, K., Nguyen, D. T., Ludlow, M., Osterhaus, A. D. M. E. and Duprex, W. P. (2017) ‘Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection’, npj Vaccines, 2(1). doi: 10.1038/s41541-017-0022-8.en_US
dc.publisherNature Researchen_US
dc.rightsCopyright The Authors 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
dc.subjectLive attenuated vaccinesen_US
dc.subjectViral infectionen_US
dc.titleNeedle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protectionen_US
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