Phenomenological Modeling of Antibody Response from Vaccine Strain Composition

The elicitation of broadly neutralizing antibodies (bnAbs) is a major goal of vaccine design for highly mutable pathogens, such as influenza, HIV, and coronavirus. Although many rational vaccine design strategies for eliciting bnAbs have been devised, their efficacies need to be evaluated in preclinical animal models and in clinical trials. To improve outcomes for such vaccines, it would be useful to develop methods that can predict vaccine efficacies against arbitrary pathogen variants. As a step in this direction, here, we describe a simple biologically motivated model of antibody reactivity elicited by nanoparticle-based vaccines using only antigen amino acid sequences, parametrized with a small sample of experimental antibody binding data from influenza or SARS-CoV-2 nanoparticle vaccinations. <b>Results</b>: The model is able to recapitulate the experimental data to within experimental uncertainty, is relatively insensitive to the choice of the parametrization/training set, and provides qualitative predictions about the antigenic epitopes exploited by the vaccine, which are testable by experiment. For the mosaic nanoparticle vaccines considered here, model results suggest indirectly that the sera obtained from vaccinated mice contain bnAbs, rather than simply different strain-specific Abs. Although the present model was motivated by nanoparticle vaccines, we also apply it to a mutlivalent mRNA flu vaccination study, and demonstrate good recapitulation of experimental results. This suggests that the model formalism is, in principle, sufficiently flexible to accommodate different vaccination strategies. Finally, we show how the model could be used to rank the efficacies of vaccines with different antigen compositions. <b>Conclusions</b>: Overall, this study suggests that simple models of vaccine efficacy parametrized with modest amounts of experimental data could be used to compare the effectiveness of designed vaccines.