Abstract
Influenza viruses cause significant mortality in humans, especially among people 65 years and older. The outbreaks of A(H3N2) influenza viruses or viruses of vaccine-mismatched strains are usually associated with more severe diseases in elderly population. Vaccination is the practical countermeasure for controlling influenza virus infection in humans. However, the immune responses elicited by current influenza vaccines in elderly are not as robust as those responses elicited in younger adults. There is an urgent need for a universal influenza virus vaccine that can induce broadly protective immunity against viral infection in elderly individuals. Currently, influenza virus vaccines that target conserved epitopes on a variety of influenza virus antigens are under evaluation. However, almost all these vaccine candidates are evaluated in adult animal models. In this study, we evaluated Computationally Optimized Broadly Reactive Antigen (COBRA)-based influenza vaccines in elderly ferrets with pre-existing immunity to historical influenza viruses to assess the breadth of vaccine induced protective antibody responses. Vaccination of elderly ferrets with Infectimune® adjuvanted mixtures of COBRA hemagglutinin (HA) and neuraminidase (NA) recombinant protein vaccines elicited robust binding antibodies against all components in the vaccine. Vaccine formulations with multiple H3 COBRA HA components significantly enhanced hemagglutination-inhibition (HAI) activity against H3N2 viruses. In addition, elderly ferrets vaccinated with multivalent COBRA HA and NA vaccines were protected from infection with reduced nasal virus shedding. Overall, a multivalent COBRA HA and NA vaccine may be an effective vaccine strategy to reduce morbidity and mortality in the elderly.