Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza.
<h4>Unlabelled</h4>The recent swine H1N1 influenza outbreak demonstrated that egg-based vaccine manufacturing has an Achille's heel: its inability to provide a large number of doses quickly. Using a novel manufacturing platform based on transient expression of influenza surface glyc...
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2010
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oai:doaj.org-article:ca8e93613f84474b8fe3ee1da465d8922021-11-18T07:01:20ZPreclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza.1932-620310.1371/journal.pone.0015559https://doaj.org/article/ca8e93613f84474b8fe3ee1da465d8922010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21203523/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Unlabelled</h4>The recent swine H1N1 influenza outbreak demonstrated that egg-based vaccine manufacturing has an Achille's heel: its inability to provide a large number of doses quickly. Using a novel manufacturing platform based on transient expression of influenza surface glycoproteins in Nicotiana benthamiana, we have recently demonstrated that a candidate Virus-Like Particle (VLP) vaccine can be generated within 3 weeks of release of sequence information. Herein we report that alum-adjuvanted plant-made VLPs containing the hemagglutinin (HA) protein of H5N1 influenza (A/Indonesia/5/05) can induce cross-reactive antibodies in ferrets. Even low doses of this vaccine prevented pathology and reduced viral loads following heterotypic lethal challenge. We further report on safety and immunogenicity from a Phase I clinical study of the plant-made H5 VLP vaccine in healthy adults 18-60 years of age who received 2 doses 21 days apart of 5, 10 or 20 µg of alum-adjuvanted H5 VLP vaccine or placebo (alum). The vaccine was well tolerated at all doses. Adverse events (AE) were mild-to-moderate and self-limited. Pain at the injection site was the most frequent AE, reported in 70% of vaccinated subjects versus 50% of the placebo recipients. No allergic reactions were reported and the plant-made vaccine did not significantly increase the level of naturally occurring serum antibodies to plant-specific sugar moieties. The immunogenicity of the H5 VLP vaccine was evaluated by Hemagglutination-Inhibition (HI), Single Radial Hemolysis (SRH) and MicroNeutralisation (MN). Results from these three assays were highly correlated and showed similar trends across doses. There was a clear dose-response in all measures of immunogenicity and almost 96% of those in the higher dose groups (2 × 10 or 20 µg) mounted detectable MN responses. Evidence of striking cross-protection in ferrets combined with a good safety profile and promising immunogenicity in humans suggest that plant-based VLP vaccines should be further evaluated for use in pre-pandemic or pandemic situations.<h4>Trial registration</h4>ClinicalTrials.gov NCT00984945.Nathalie LandryBrian J WardSonia TrépanierEmanuele MontomoliMichèle DargisGiulia LapiniLouis-P VézinaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15559 (2010) |
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Medicine R Science Q Nathalie Landry Brian J Ward Sonia Trépanier Emanuele Montomoli Michèle Dargis Giulia Lapini Louis-P Vézina Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. |
| description |
<h4>Unlabelled</h4>The recent swine H1N1 influenza outbreak demonstrated that egg-based vaccine manufacturing has an Achille's heel: its inability to provide a large number of doses quickly. Using a novel manufacturing platform based on transient expression of influenza surface glycoproteins in Nicotiana benthamiana, we have recently demonstrated that a candidate Virus-Like Particle (VLP) vaccine can be generated within 3 weeks of release of sequence information. Herein we report that alum-adjuvanted plant-made VLPs containing the hemagglutinin (HA) protein of H5N1 influenza (A/Indonesia/5/05) can induce cross-reactive antibodies in ferrets. Even low doses of this vaccine prevented pathology and reduced viral loads following heterotypic lethal challenge. We further report on safety and immunogenicity from a Phase I clinical study of the plant-made H5 VLP vaccine in healthy adults 18-60 years of age who received 2 doses 21 days apart of 5, 10 or 20 µg of alum-adjuvanted H5 VLP vaccine or placebo (alum). The vaccine was well tolerated at all doses. Adverse events (AE) were mild-to-moderate and self-limited. Pain at the injection site was the most frequent AE, reported in 70% of vaccinated subjects versus 50% of the placebo recipients. No allergic reactions were reported and the plant-made vaccine did not significantly increase the level of naturally occurring serum antibodies to plant-specific sugar moieties. The immunogenicity of the H5 VLP vaccine was evaluated by Hemagglutination-Inhibition (HI), Single Radial Hemolysis (SRH) and MicroNeutralisation (MN). Results from these three assays were highly correlated and showed similar trends across doses. There was a clear dose-response in all measures of immunogenicity and almost 96% of those in the higher dose groups (2 × 10 or 20 µg) mounted detectable MN responses. Evidence of striking cross-protection in ferrets combined with a good safety profile and promising immunogenicity in humans suggest that plant-based VLP vaccines should be further evaluated for use in pre-pandemic or pandemic situations.<h4>Trial registration</h4>ClinicalTrials.gov NCT00984945. |
| format |
article |
| author |
Nathalie Landry Brian J Ward Sonia Trépanier Emanuele Montomoli Michèle Dargis Giulia Lapini Louis-P Vézina |
| author_facet |
Nathalie Landry Brian J Ward Sonia Trépanier Emanuele Montomoli Michèle Dargis Giulia Lapini Louis-P Vézina |
| author_sort |
Nathalie Landry |
| title |
Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. |
| title_short |
Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. |
| title_full |
Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. |
| title_fullStr |
Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. |
| title_full_unstemmed |
Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. |
| title_sort |
preclinical and clinical development of plant-made virus-like particle vaccine against avian h5n1 influenza. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/ca8e93613f84474b8fe3ee1da465d892 |
| work_keys_str_mv |
AT nathalielandry preclinicalandclinicaldevelopmentofplantmadeviruslikeparticlevaccineagainstavianh5n1influenza AT brianjward preclinicalandclinicaldevelopmentofplantmadeviruslikeparticlevaccineagainstavianh5n1influenza AT soniatrepanier preclinicalandclinicaldevelopmentofplantmadeviruslikeparticlevaccineagainstavianh5n1influenza AT emanuelemontomoli preclinicalandclinicaldevelopmentofplantmadeviruslikeparticlevaccineagainstavianh5n1influenza AT micheledargis preclinicalandclinicaldevelopmentofplantmadeviruslikeparticlevaccineagainstavianh5n1influenza AT giulialapini preclinicalandclinicaldevelopmentofplantmadeviruslikeparticlevaccineagainstavianh5n1influenza AT louispvezina preclinicalandclinicaldevelopmentofplantmadeviruslikeparticlevaccineagainstavianh5n1influenza |
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