A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response

Background: Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (IM) or intranasally (IN) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either IM or IN in young and aged mice. Methods: Young adult (5-8 weeks) and aged (16-20 months) female BALB/c mice received a single 3μg dose based on HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (IM or IN), split-virion vaccine (IM) or left naive. After vaccination, humoral and splenocyte responses were assessed and some mice were challenged. Results: Both VLP and split vaccines given IM protected 100% of the young animals but the VLP group lost the least weight, and had stronger humoral and cellular responses. Compared to split vaccine recipients, aged animals vaccinated IM with VLP were more likely to survive challenge (80% vs. 60%). Lung viral load post-challenge was lowest in the VLP IM groups. Mice vaccinated with VLP IN made little detectable immune responses but survival was significantly increased. Conclusion: In both age groups, IM administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the split-virion vaccine.