Vaccination does not protect aged mice from influenza-induced lung inflammation (VAC9P.1062)

Aging predisposes individuals to increased susceptibility to influenza infection and delays in viral clearance. Importantly, we show that age-related delays in viral clearance are correlated with lingering inflammation in the lungs of aged mice. This is critical since inflammation in the lungs is associated with an enhanced susceptibility to secondary bacterial infection, which is a significant sequela to flu infection and often causes death. Inflammation in young lungs following flu infection can be significantly reduced by prior flu immunity, such as that generated following vaccination with recombinant influenza nucleoprotein (rNP). This protection is characterized by reduced lung inflammation, reduced lung damage, reduced susceptibility to flu challenge and also correlates with increased levels of IL-10 and anti-NP antibodies. In contrast, vaccination of aged mice with rNP does not reduce lung inflammation and shows no protection from weight loss and no reduction in viral titers in the lungs following subsequent flu infection. Additionally, aged mice generate lower levels of NP-specific antibodies, which are absolutely critical for reducing lung inflammation. Consequently, unlike young mice, these NP vaccinated aged mice are not protected from death due to secondary bacterial infection. Thus, when considering a universal flu vaccine such as rNP, it is important to understand how efficacious it can be in highly susceptible populations such as the elderly.