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Modified vaccinia virus ankara preferentially targets antigen presenting cells in vitro, ex vivo and in vivo

Altenburg, Arwen F.
; 
van de Sandt, Carolien E.
; 
Li, Bobby W. S.
; 
MacLoughlin, Ronan J.
; 
Fouchier, Ron A. M.
; 
van Amerongen, Geert
; 
Volz, Asisa
; 
Hendriks, Rudi W.
; 
de Swart, Rik L.
; 
Sutter, Gerd
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Repository DOI
Publication Date
2017-08-17
Keywords
candidate tuberculosis vaccine, attenuated influenza vaccine, human alveolar macrophages, dendritic cells, protein binds, t-cells, mva, immunogenicity, aerosol, vector
Type
Article
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Citation
Altenburg, Arwen F. van de Sandt, Carolien E.; Li, Bobby W. S.; MacLoughlin, Ronan J.; Fouchier, Ron A. M.; van Amerongen, Geert; Volz, Asisa; Hendriks, Rudi W.; de Swart, Rik L.; Sutter, Gerd; Rimmelzwaan, Guus F.; de Vries, Rory D. (2017). Modified vaccinia virus ankara preferentially targets antigen presenting cells in vitro, ex vivo and in vivo . Scientific Reports 7 ,
Abstract
Modified Vaccinia virus Ankara (MVA) is a promising vaccine vector with an excellent safety profile. However, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of MVA, especially in relevant animal species. Here, we performed in vitro, ex vivo and in vivo experiments with recombinant MVA expressing green fluorescent protein (rMVA-GFP). In both human peripheral blood mononuclear cells and mouse lung explants, rMVA-GFP predominantly infected antigen presenting cells. Subsequent in vivo experiments performed in mice, ferrets and non-human primates indicated that preferential targeting of dendritic cells and alveolar macrophages was observed after respiratory administration, although subtle differences were observed between the respective animal species. Following intramuscular injection, rMVA-GFP was detected in interdigitating cells between myocytes, but also in myocytes themselves. These data are important in advancing our understanding of the basis for the immunogenicity of MVA-based vaccines and aid rational vaccine design and delivery strategies.
Funder
Publisher
Springer Nature
Publisher DOI
10.1038/s41598-017-08719-y
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)