Integrative representations and analyses of vaccine-induced intended protective immunity and unintended adverse events using ontology-based and theory-guided approaches.

While effective preventive vaccines induce intended protective immunity, they also induce unintended adverse events (AEs). Generally speaking, compared to killed, inactivated vaccines and protein vaccines, live attenuated vaccines induce more protective immune responses. However, live attenuated vaccines are also associated with more AEs and even more serious AEs. For example, while live attenuated smallpox vaccines were critical to the eradication of smallpox, approximately 20– 30% of smallpox vaccine recipients also experienced with various AEs that range in prevalence and severity [1]. Inter-individual variations in cytokine and AE response after smallpox vaccinations are in part due to genetic variation. For another example, the attenuated oral poliovirus vaccine (OPV) efficiently induces intestinal immunity and durable humoral immunity. However, OPV has the disadvantage of genetic instability, contributing to rare and sporadic cases of vaccineassociated paralytic poliomyelitis and the emergence of genetically divergent vaccine-derived polioviruses [2]. These AEs are worsened in patients with primary immunodeficiencies. These results suggest that the intended protective immune responses and unintended adverse events are correlated and deserve being studied simultaneously.