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PLoS One. 2019 Jan 10;14(1):e0210009. doi: 10.1371/journal.pone.0210009. eCollection 2019.

A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities.

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Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.
Medicago Inc., Quebec, Quebec, Canada.



The elderly are at high risk from influenza, in part because immunity wanes with age and through the accumulation of comorbidities. A novel plant-derived virus-like-particle (VLP) vaccine bearing influenza hemagglutinin can induce a balanced humoral and cellular response in old mice (16-18 months) while split virion vaccines elicit mostly antibodies. Because mice also collect comorbidities and lose immune competence as they age, we wished to determine how the plant-derived VLP vaccine would perform in animals approaching the end of their life-span.


Old (24-26 months) female BALB/c mice received two intramuscular doses of H1-VLP vaccine, an inactivated H1N1 vaccine (IIV) (both based on A/H1N1/California/07/09) (3μg each) or PBS. Serum was collected on day 42 and humoral responses were measured by enzyme-linked immunosorbent assay (ELISA), microneutralization (MN) and hemagglutination inhibition (HI) assays. Influenza-specific splenocyte CD4+ & CD8+ T cell responses were measured by flow cytometry. Full body computed tomography (CT) and structured necropsies were performed on day 42. Comorbidities including reduced lung volume (kyphosis), masses, abscesses, etc. were assessed using a standard scoring system (1-21) and mice with scores ≥5 were considered to have important comorbidities.


Overall, 53.3% of the animals had significant comorbidities. Three weeks post-boost, HI and MN titres were mostly undetectable but ELISA titres were significantly higher in the H1-VLP animals compared to the IIV group (GMT (95% CI): 961 (427, 2163) vs 425 (200, 903): p = 0.03). Both CD4+(TNFα, IFNγ) and CD8+ (IFNγ) T cell responses were also greater in the H1-VLP group than the IIV.


Even in very old mice with comorbidities, the plant-made H1-VLP vaccine elicited a stronger and more balanced immune response than IIV. Animals with fewer comorbidities tended to have the better composite (humoral and cellular) responses. These novel vaccines have the potential to address some of the limitations of current vaccines in the elderly.

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Conflict of interest statement

BJW has served as the medical officer for Medicago Inc since 2011 and has held peer-reviewed grants with the company from various sources. SP and NL are currently both employees at Medicago Inc. This study was partly co-funded by an academic-industry team award led by BJW that was co-funded by Medicago Inc and the Ministère des Finances et de l’Économie du Québec with project oversight by Genome Quebec. The company also provided research materials and other 'in-kind' support for the work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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