Immunological assessment of influenza vaccines and immune correlates of protection

Influenza vaccines remain the primary public health tool in reducing the ever-present burden of influenza and its complications. In seeking more immunogenic, more effective and more broadly cross-protective influenza vaccines, the landscape of influenza vaccines is rapidly expanding, both in near-term advances and next-generation vaccine design. Although the first influenza vaccines were licensed over 60 years ago, the hemagglutination-inhibition antibody titer is currently the only universally accepted immune correlate of protection against influenza. However, hemagglutination-inhibition titers appear to be less effective at predicting protection in populations at high risk for severe influenza disease; older adults, young children and those with certain medical conditions. The lack of knowledge and validated methods to measure alternate immune markers of protection against influenza remain a substantial barrier to the development of more immunogenic, broadly cross-reactive and effective influenza vaccines. Here, the authors review the knowledge of immune effectors of protection against influenza and discuss assessment methods for a broader range of immunological parameters that could be considered in the evaluation of traditional or new-generation influenza vaccines.