Elderly individuals are highly susceptible to influenza virus-mediated disease. In fact, the CDC estimates that 71-85% of the deaths that occur in the U.S. as a result of complications of influenza virus infection occur in those over 65 years of age. Although the flu vaccine can provide significant protection to the population as a whole, it is poorly effective in the elderly. This is likely the result of the impaired immunity present in this group. While a high dose option has been developed, efficacy is still lower than desired and the 4-fold increase in dose significantly increases the cost of the vaccine as well as the ability to rapidly produce it if needed. We have developed an influenza vaccine approach that is comprised of inactivated A/Puerto Rico/8/1934 influenza virus coupled to the TLR7/8 agonist resiquimod (R848). We have shown this vaccine to be highly stimulatory in a neonate NHP model. Here we present compelling data that a second generation vaccine based on this approach is capable of quantitatively and qualitatively increasing DC maturation and cytokine production in DC from elderly human donors and NHP, providing rationale that it may be an effective vaccine in vivo. The vaccine will be tested in a cohort of aged NHP (17-22 years old). These animals approximate humans between the ages of 68 and 88. The results from these studies will provide the critical information needed to determine the potential utility of this vaccine approach. We also propose mechanistic studies using DC from elderly human donors to understand how our vaccine promotes the robust stimulation observed. This will provide novel insights into the mechanism through which improved DC maturation can be obtained.
In spite of the overall success of currently approved vaccines, there are groups within the population which pose significant challenges with regard to effective vaccination. Among these are elderly individuals. Here we explore the utility of a novel vaccine for influenza in mechanistic studies with human cells and an elderly nonhuman primate model.