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Vaccine-induced protection of rhesus macaques against plasma viremia after intradermal infection with a European lineage 1 strain of West Nile virus.

Verstrepen BE, Oostermeijer H, Fagrouch Z, van Heteren M, Niphuis H, Haaksma T, Kondova I, Bogers WM, de Filette M, Sanders N, Stertman L, Magnusson S, Lőrincz O, Lisziewicz J, Barzon L, Palù G, Diamond MS, Chabierski S, Ulbert S, Verschoor EJ - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.

ABSTRACT
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.

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Related in: MedlinePlus

Study outline.Schematic representation of the study with two West Nile virus vaccine strategies. Group 1 received three immunizations with recombinant E protein adjuvanted with Matrix-M (red triangles) at indicated study weeks. Group 2 received one immunization of WNV-DermaVir (green triangle), followed by two immunizations with recombinant E protein adjuvanted with Matrix-M (red triangles). Nine weeks after the last immunization, all animals (including controls) were challenged intradermally with 2×105 TCID50 of WNV-Ita09. All animals were euthanized 14 days post-challenge (study week 17).
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pone-0112568-g001: Study outline.Schematic representation of the study with two West Nile virus vaccine strategies. Group 1 received three immunizations with recombinant E protein adjuvanted with Matrix-M (red triangles) at indicated study weeks. Group 2 received one immunization of WNV-DermaVir (green triangle), followed by two immunizations with recombinant E protein adjuvanted with Matrix-M (red triangles). Nine weeks after the last immunization, all animals (including controls) were challenged intradermally with 2×105 TCID50 of WNV-Ita09. All animals were euthanized 14 days post-challenge (study week 17).

Mentions: A schematic outline of the study is given in Figure 1. The animals in group 1 were immunized via three consecutive intramuscular (IM) injections of 20 µg WNV-E mixed with 25 µg Matrix-M at weeks 0, 3 and 6. The animals in group 2 received 100 µg WNV-DermaVir at week 0, given as 8 intradermal injections of 100 µl each in the upper back. Subsequently, the animals were boosted twice at weeks 3 and 6 with 20 µg WNV-E mixed with 25 µg Matrix-M. Nine weeks after the last immunization, all animals, including those in the infection control group (group 3), were challenged by an intradermal injection in the upper back of 2×105 TCID50 of WNV lineage 1a strain Ita09 [46] in 100 µl saline. This dose was found previously to productively infect rhesus macaques [28]. After WNV infection, the animals were observed daily for general condition, appetite, and stool until the end of the study, i.e. 14 days post-challenge.


Vaccine-induced protection of rhesus macaques against plasma viremia after intradermal infection with a European lineage 1 strain of West Nile virus.

Verstrepen BE, Oostermeijer H, Fagrouch Z, van Heteren M, Niphuis H, Haaksma T, Kondova I, Bogers WM, de Filette M, Sanders N, Stertman L, Magnusson S, Lőrincz O, Lisziewicz J, Barzon L, Palù G, Diamond MS, Chabierski S, Ulbert S, Verschoor EJ - PLoS ONE (2014)

Study outline.Schematic representation of the study with two West Nile virus vaccine strategies. Group 1 received three immunizations with recombinant E protein adjuvanted with Matrix-M (red triangles) at indicated study weeks. Group 2 received one immunization of WNV-DermaVir (green triangle), followed by two immunizations with recombinant E protein adjuvanted with Matrix-M (red triangles). Nine weeks after the last immunization, all animals (including controls) were challenged intradermally with 2×105 TCID50 of WNV-Ita09. All animals were euthanized 14 days post-challenge (study week 17).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231036&req=5

pone-0112568-g001: Study outline.Schematic representation of the study with two West Nile virus vaccine strategies. Group 1 received three immunizations with recombinant E protein adjuvanted with Matrix-M (red triangles) at indicated study weeks. Group 2 received one immunization of WNV-DermaVir (green triangle), followed by two immunizations with recombinant E protein adjuvanted with Matrix-M (red triangles). Nine weeks after the last immunization, all animals (including controls) were challenged intradermally with 2×105 TCID50 of WNV-Ita09. All animals were euthanized 14 days post-challenge (study week 17).
Mentions: A schematic outline of the study is given in Figure 1. The animals in group 1 were immunized via three consecutive intramuscular (IM) injections of 20 µg WNV-E mixed with 25 µg Matrix-M at weeks 0, 3 and 6. The animals in group 2 received 100 µg WNV-DermaVir at week 0, given as 8 intradermal injections of 100 µl each in the upper back. Subsequently, the animals were boosted twice at weeks 3 and 6 with 20 µg WNV-E mixed with 25 µg Matrix-M. Nine weeks after the last immunization, all animals, including those in the infection control group (group 3), were challenged by an intradermal injection in the upper back of 2×105 TCID50 of WNV lineage 1a strain Ita09 [46] in 100 µl saline. This dose was found previously to productively infect rhesus macaques [28]. After WNV infection, the animals were observed daily for general condition, appetite, and stool until the end of the study, i.e. 14 days post-challenge.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus