Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection
Date
2017-08-01
Journal Title
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Volume Title
Publisher
Nature Research
Abstract
Needle-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.
Description
Publication history: Accepted - 8 June 2017; Published online - 1 August 2017.
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Article
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Keywords
Live attenuated vaccines, Viral infection
Citation
de 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.