Title |
Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza
|
---|---|
Published in |
PLOS ONE, December 2010
|
DOI | 10.1371/journal.pone.0015559 |
Pubmed ID | |
Authors |
Nathalie Landry, Brian J. Ward, Sonia Trépanier, Emanuele Montomoli, Michèle Dargis, Giulia Lapini, Louis-P. Vézina |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Canada | 3 | 1% |
India | 2 | <1% |
Argentina | 2 | <1% |
Egypt | 1 | <1% |
Germany | 1 | <1% |
Denmark | 1 | <1% |
Japan | 1 | <1% |
Unknown | 225 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 45 | 19% |
Researcher | 35 | 15% |
Student > Bachelor | 35 | 15% |
Student > Master | 29 | 12% |
Other | 14 | 6% |
Other | 39 | 17% |
Unknown | 39 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 75 | 32% |
Biochemistry, Genetics and Molecular Biology | 42 | 18% |
Medicine and Dentistry | 25 | 11% |
Immunology and Microbiology | 11 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 8 | 3% |
Other | 35 | 15% |
Unknown | 40 | 17% |