Correlates of protection against influenza

Correlates of protection for influenza virus have not been fully defined, but it is widely believed that protection against influenza can be conferred by serum haemagglutinin (HA) antibodies. The immune responses to injected influenza vaccines are routinely assessed using titration of serological HA antibodies. It is generally accepted that neutralizing and HA antibodies, as well as antibodies to neuraminidase, can be detected in serum after 3–4 weeks post primary infection or vaccination. Serological assays commonly used to quantify antibodies specific for influenza viruses include haemagglutination inhibition (HI), single radial hemolysis (SRH), microneutralization (MN), ELISA and Western blot, of which historically HI and SRH were the most widely applied methods, the latter increasingly replaced by MN. Each method used for antibodies titration has different characteristics, and the validity index and specific use (seroepidemiology, serodiagnosis, response to vaccination, etc.) have to be considered to select the most suitable one. Recently, ELISA tests have been improved thanks to the discovery of the HA structure and availability of this protein after recombinant expression. While the number of data collected by conventional assays (HI and SRH) has permitted a fairly good optimization, serological measures are used to characterize the number of antibodies before and after vaccination. HI is the assay used most frequently for influenza antibody titration; however, it has low sensitivity in detecting responses to avian viruses in mammalian sera and alternative serological tests are needed. SRH utilizes a complement-mediated hemolysis reaction to measure the amount of antibody. This test appears to be as sensitive as the MN assay. HI and SRH assays are not functional tests for measuring immunity to influenza and suffers from several technical drawbacks. Improvements of these assays will be a further step in preparation of new influenza vaccines, particularly for cell-derived products. Additional immunological assessments, such as cell-mediated immunity and the role of neuraminidase, need to be explored to give more insight into the overall effects of vaccination.