Vaccine-induced protection of rhesus macaques against plasma viremia after intradermal infection with a European lineage 1 strain of West Nile virus.
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.
Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
Babs E
BE
Verstrepen
Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
Herman
H
Oostermeijer
Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
Zahra
Z
Fagrouch
Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
Melanie
M
van Heteren
Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
Henk
H
Niphuis
Animal Science Department, Division of Pathology and Microbiology, BPRC Rijswijk, The Netherlands.
Tom
T
Haaksma
Animal Science Department, Division of Pathology and Microbiology, BPRC Rijswijk, The Netherlands.
Ivanela
I
Kondova
Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
Willy M
WM
Bogers
Laboratory of Gene Therapy, Faculty of Veterinary Sciences, Ghent University, Merelbeke, Belgium.
Marina
M
de Filette
Laboratory of Gene Therapy, Faculty of Veterinary Sciences, Ghent University, Merelbeke, Belgium.
Niek
N
Sanders
Novavax AB, Uppsala, Sweden.
Linda
L
Stertman
Novavax AB, Uppsala, Sweden.
Sofia
S
Magnusson
eMMUNITY, Inc., Budapest, Hungary.
Orsolya
O
Lőrincz
eMMUNITY, Inc., Budapest, Hungary.
Julianna
J
Lisziewicz
Department of Molecular Medicine, University of Padova, Padova, Italy.
Luisa
L
Barzon
Department of Molecular Medicine, University of Padova, Padova, Italy.
Giorgio
G
Palù
Departments of Medicine, Molecular Microbiology and Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Michael S
MS
Diamond
Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
Stefan
S
Chabierski
Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
Sebastian
S
Ulbert
Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
Ernst J
EJ
Verschoor
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D009033:Culicidae; D005060:Europe; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000276:immunology; D008253:Macaca mulatta; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000276:immunology; D014901:West Nile Fever / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000627:therapeutic use*; D014902:West Nile virus / Q000145:classification*
D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; D053060:West Nile Virus Vaccines; D007371:Interferon-gamma