Systems vaccinology and big data in the vaccine development chain

Raeven, René H. M.; van Riet, Elly; Meiring, Hugo D.; Metz, Bernard; Kersten, Gideon F. A.

but in the context of systems vaccinology, not only antibody quantity, but also functionality is increasingly investigated. Antibodies may inhibit other functional antibodies or enhance disease by facilitating virus entry into cells. However, non-neutralizing antibodies may still be functional and could have more impact on protection from disease than neutralizing antibodies, for instance by interaction of the antibody constant domain with Fc receptors. This interaction is determined by two characteristics, antibody subclass (irreversible) and antibody glycosylation (fast and reversible) that can for example impact the affinity for Fc receptors. 67 The glycosylation profile of antigen-specific antibodies is changed upon vaccination, whereas the glycosylation profile of total IgG is not affected. Interestingly, despite very different pre-vaccination glycosylation levels in populations in different parts of the world, 68 profiles induced by vaccination are similar, as was shown after influenza vaccination. 69 However, different vaccine formulations can induce different glycosylation profiles. 68 This is likely also influenced by the adjuvant present in the formulation, either directly or via cytokine induction. 70 Though the biological implications of these differences are not yet clear, the recent developments in systems serology demonstrate that multiple parameters of the antibody response, such as IgG subtype and antibody glycosylation among others, influence antibody functionally and therefore vaccine efficacy. [71] [72] [73]