Reverse vaccinology 2.0: Human immunology instructs vaccine antigen design

Rappuoli, Rino; Bottomley, Matthew J.; D’Oro, Ugo; Finco, Oretta; De Gregorio, Ennio

Finally, in recent studies, the sequencing of paired VH/ VL Ig gene repertoire by next-generation sequencing technology has been combined with novel proteomic methods mining the antigen-specific Ab repertoire that comprises the human serum polyclonal response (Wine et al., 2015) . The new perspective offered by combining the analysis of the B cell and Ab repertoire induced by TT vaccination has highlighted that the anti-TT serum IgG repertoire is composed of a limited number of Ab clonotypes (80-100), whereas the B cell receptor repertoire diversity in the memory and plasmablast compartments is orders of magnitude greater than that of the serological repertoire (Lavinder et al., 2014) . This observation suggests that most peripheral B cell-encoded Abs are unlikely to be present in detectable amounts as soluble proteins, leaving unanswered questions regarding the nature and dynamics of the elements regulating the serological memory. Collectively, all of the technologies that allow the dissection of the human Ab response to pathogens are increasing our understanding of how protection is induced and can drive the design of more efficacious antigens for the development of vaccines to prevent current and future pathogenic threats.