EFFICACY OF INFLUENZA VLPS
The pandemic H5 VLP vaccine product has been tested for safety and immunogenicity in a completed Phase I clinical trial and
an ongoing Phase II trial in Canada. The Phase I results demonstrated that the vaccine product was safe and well tolerated
and did not induce allergenic responses. No increase in the level of naturally occurring serum antibodies to plant N-glycans
was observed. The evaluation of immune response to VLP immunization by hemagglutination-inhibition, single-radial hemolysis,
and microneutralization assays were well correlated and showed a clear dose-response (3). In the Phase II trial, the preliminary
results showed 65% seroprotection and 65% seroconversion after the administration of two 20-μg doses to 18 to 49 year-old
Today, the globalization of trade and the amount of international travel provide many opportunities for infectious diseases
to spread rapidly and globally. As seen with the outbreak of the 2009 A–H1N1 influenza, within two days of the first confirmed
cases from Mexico, the virus was reported in five additional countries. Because of difficulties in producing the vaccine,
initial doses became available only after 26 weeks in the US, and supplies for the protection of all US citizens would have
taken almost a year to produce. The President's Council of Advisors on Science and Technology stated that more than 2000 lives—with
an average age of less than 40—could have been saved if vaccination had begun even one month earlier (5).
This increasing risk is posing new challenges to public-health agencies around the globe and stressing the need for effective
vaccines sourced from highly flexible manufacturing facilities that can be mobilized rapidly and cost-effectively. The greatest
potential to meet this challenge lies in the use of recombinant DNA technologies.
Medicago is pursuing a promising alternative approach that combines the speed of transient-expression technology with the
efficacy of VLPs as antigen-presentation scaffolds. The company's manufacturing platform offers surge capacity and cost advantages
over recombinant technologies, such as mammalian and insect cells. The technology can deliver a vaccine for testing in less
than a month after the disclosure of genetic sequences from a pandemic strain, as demonstrated by the first doses of plant-made
H1 VLP candidate vaccine that were produced at the onset of the 2009 pandemic. This production time frame thus has the potential
to allow the vaccination of a population before the first wave of a pandemic strikes, and therefore to supply large volumes
of vaccine to the world market.
In the past five years, Medicago has successfully developed this technology from the bench scale to the pilot scale according
to cGMP. The compnay is now transitioning into large-scale manufacturing. Since 2008, Medicago has operated a 24,000-ft2 pilot clinical cGMP facility located in Québec City. This facility includes 10,000 ft2 of high-tech contained plant biomass production space, as well as 14,000 ft2 of cGMP manufacturing units for plant manipulation, product recovery, and purification.
In August 2010, Medicago began building a 97,000-ft2 cGMP facility in Research Triangle Park, North Carolina. Designed to produce 10 million doses of pandemic influenza vaccine
per month, this facility will include a fully automated and contained plant biomass production facility and a state-of-the-art
extraction-and-purification unit. On an annual basis, this facility would have a production capacity of 40 million doses of
seasonal-trivalent influenza vaccine or 120 million doses of pandemic-influenza vaccine. The facility will be built in a 12-month
timeframe at a cost of less than $35 million.
The capacity, speed of construction, and low cost of Medicago's large-scale facility clearly illustrates the promises of the
company's manufacturing platform. These factors, in addition to the interim Phase II clinical results of Medicago's first
enveloped VLP vaccine, could form the basis for a fast, high-quality, and cost-effective manufacturing solution to address
the needs for improved 21st-century vaccines.
LOUIS-P. VÉZINA* is vice-president and chief scientific officer, MARC-ANDRÉ D'AOUST is director of innovative technology, NATHALIE LANDRY is vice-president of product development, MANON M.J. COUTURE is director of new products, NATHALIE CHARLAND is director of product portfolio, FRÉDÉRIC ORS is vice-president of business development, BRIGITTE BARBEAU is vice-president of operations, and ANDY J. SHELDON is president and chief executive officer, all at Medicago, 1020 Route de l'Eglise, Suite 600, Québec, QC, Canada, G1V 3V9,
1. O. Wyman and the Program for Appropriate Technology in Health, "Influenza Vaccine Strategies for Broad Global Access,"
(PATH, Washington, DC, 2007).
2. M.A. D'Aoust et al., Plant Biotechnol. J.
6 (9), 930–940 (2008).
3. N. Landry, PLoS ONE
5 (12), e15559 (2010).
4. E.V.L. Grgacic and D.A. Anderson, Methods
40 (1), 60–65 (2006).
5. President's Council of Advisors on Science and Technology, "Report to the President on Reengineering the Influenza Vaccine
Production Enterprise to Meet the Challenges of Pandemic Influenza" (Washington, DC, August 2010).