Seroprotection Rate, Mean Fold Increase, Seroconversion Rate: Which Parameter Adequately Expresses Seroresponse to Influenza Vaccination?

Serological parameters intend to describe antibody response to influenza vaccine in a population. However, there is uncertainty about the mathematical appropriateness and the biological or clinical meaning of conventionally used parameters. Theoretical considerations and exploration of a data-set of 16 studies with an inactivated (subunit) influenza vaccine involving 1176 adult subjects suggest the following conclusions. In a population seronegative before vaccination, the post-vaccination geometric mean titre (post-GMT) is a meaningful immunological parameter adequately expressing antibody response after vaccination. The related protection rate (PR) is a good surrogate parameter for protection provided by a given vaccine, thus relevant to public health. However, in a population partially seropositive before vaccination (due to previous exposition to influenza antigens), the same parameters may, under certain conditions, seriously overestimate the antibody response, as they do not account for the pre-vaccination state. Conventional attempts to address pre-vaccination antibody are associated with either loss of information (exclusion of seropositive subjects) or incomplete control of pre-vaccination state (mean fold increase (MFI), response rate (RR)). Although not devoid of theoretical limitations (heteroscedasticity), correction of post-GMT and PR by linear regression appears to provide better estimates of antibody response and vaccine immunogenicity.