Inflation in epidemiology: “The proof and measurement of association between two things” revisited

To assess the response to vaccination, quantity (concentration) and quality (avidity) of neutralizing antibodies are the most important parameters. Specifically, an increase in avidity indicates germinal center formation, which is required for establishing long-term protection. For influenza, the classical hemagglutination inhibition (HI) assay, however, quantifies a combination of both and to separately determine avidity requires high experimental effort. Here, we present a biophysical model that infers neutralizing IgG avidities from HI titers and IgG concentrations. We applied our model to infer IgG avidities against the pandemic 2009 H1N1 influenza virus in vaccinated hematopoietic stem cell transplantation patients (n = 45) and validated our results with independent avidity measurements. The model predicted that increased IgG concentrations mainly contribute to observed HI titer increases and that immunosuppressive treatment is associated with lower baseline avidities. Because the model requires only easy-to-establish measurements as inputs, we anticipate that it will help to disentangle causes for poor vaccination outcomes also in larger vaccine studies.