TY - JOUR
T1 - Vaccine-induced protection of rhesus macaques against plasma viremia after intradermal infection with a European lineage 1 strain of west nile virus
AU - Verstrepen, Babs E.
AU - Oostermeijer, Herman
AU - Fagrouch, Zahra
AU - Van Heteren, Melanie
AU - Niphuis, Henk
AU - Haaksma, Tom
AU - Kondova, Ivanela
AU - Bogers, Willy M.
AU - De Filette, Marina
AU - Sanders, Niek
AU - Stertman, Linda
AU - Magnusson, Sofia
AU - Lörincz, Orsolya
AU - Lisziewicz, Julianna
AU - Barzon, Luisa
AU - Palù, Giorgio
AU - Diamond, Michael S.
AU - Chabierski, Stefan
AU - Ulbert, Sebastian
AU - Verschoor, Ernst J.
N1 - Publisher Copyright:
© 2014 Verstrepen et al.
PY - 2014/11/13
Y1 - 2014/11/13
N2 - The mosquito-borne West Nile virus (WNV) causes human and animal disease with outbreaks in several parts of the world including North America, the Mediterranean countries, Central and East Europe, the Middle East, and Africa. Particularly in elderly people and individuals with an impaired immune system, infection with WNV can progress into a serious neuroinvasive disease. Currently, no treatment or vaccine is available to protect humans against infection or disease. The goal of this study was to develop a WNV-vaccine that is safe to use in these high-risk human target populations. We performed a vaccine efficacy study in non-human primates using the contemporary, pathogenic European WNV genotype 1a challenge strain, WNV-Ita09. Two vaccine strategies were evaluated in rhesus macaques (Macaca mulatta) using recombinant soluble WNV envelope (E) ectodomain adjuvanted with Matrix-M, either with or without DNA priming. The DNA priming immunization was performed with WNV-DermaVir nanoparticles. Both vaccination strategies successfully induced humoral and cellular immune responses that completely protected the macaques against the development of viremia. In addition, the vaccine was well tolerated by all animals. Overall, The WNV E protein adjuvanted with Matrix-M is a promising vaccine candidate for a non-infectious WNV vaccine for use in humans, including at-risk populations.
AB - The mosquito-borne West Nile virus (WNV) causes human and animal disease with outbreaks in several parts of the world including North America, the Mediterranean countries, Central and East Europe, the Middle East, and Africa. Particularly in elderly people and individuals with an impaired immune system, infection with WNV can progress into a serious neuroinvasive disease. Currently, no treatment or vaccine is available to protect humans against infection or disease. The goal of this study was to develop a WNV-vaccine that is safe to use in these high-risk human target populations. We performed a vaccine efficacy study in non-human primates using the contemporary, pathogenic European WNV genotype 1a challenge strain, WNV-Ita09. Two vaccine strategies were evaluated in rhesus macaques (Macaca mulatta) using recombinant soluble WNV envelope (E) ectodomain adjuvanted with Matrix-M, either with or without DNA priming. The DNA priming immunization was performed with WNV-DermaVir nanoparticles. Both vaccination strategies successfully induced humoral and cellular immune responses that completely protected the macaques against the development of viremia. In addition, the vaccine was well tolerated by all animals. Overall, The WNV E protein adjuvanted with Matrix-M is a promising vaccine candidate for a non-infectious WNV vaccine for use in humans, including at-risk populations.
UR - http://www.scopus.com/inward/record.url?scp=84911871549&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0112568
DO - 10.1371/journal.pone.0112568
M3 - Article
C2 - 25392925
AN - SCOPUS:84911871549
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 11
M1 - e112568
ER -