Ontology-Based Combinatorial Comparative Analysis of Adverse Events Associated with Killed and Live Influenza Vaccines

Abstract

Vaccine adverse events (VAEs) are adverse bodily changes occurring after vaccination. Understanding the adverse event (AE) profiles is a crucial step to identify serious AEs. Two different types of seasonal influenza vaccines have been used on the market: trivalent (killed) inactivated influenza vaccine (TIV) and trivalent live attenuated influenza vaccine (LAIV). Different adverse event profiles induced by these two groups of seasonal influenza vaccines were studied based on the data drawn from the CDC Vaccine Adverse Event Report System (VAERS). Extracted from VAERS were 37,621 AE reports for four TIVs (Afluria, Fluarix, Fluvirin, and Fluzone) and 3,707 AE reports for the only LAIV (FluMist). The AE report data were analyzed by a novel combinatorial, ontology-based detection of AE method (CODAE). CODAE detects AEs using Proportional Reporting Ratio (PRR), Chi-square significance test, and base level filtration, and groups identified AEs by ontology-based hierarchical classification. In total, 48 TIV-enriched and 68 LAIV-enriched AEs were identified (PRR>2, Chi-square score >4, and the number of cases >0.2% of total reports). These AE terms were classified using the Ontology of Adverse Events (OAE), MedDRA, and SNOMED-CT. The OAE method provided better classification results than the two other methods. Thirteen out of 48 TIV-enriched AEs were related to neurological and muscular processing such as paralysis, movement disorders, and muscular weakness. In contrast, 15 out of 68 LAIV-enriched AEs were associated with inflammatory response and respiratory system disorders. There were evidences of two severe adverse events (Guillain-Barre Syndrome and paralysis) present in TIV. Although these severe adverse events were at low incidence rate, they were found to be more significantly enriched in TIV-vaccinated patients than LAIV-vaccinated patients. Therefore, our novel combinatorial bioinformatics analysis discovered that LAIV had lower chance of inducing these two severe adverse events than TIV. In addition, our meta-analysis found that all previously reported positive correlation between GBS and influenza vaccine immunization were based on trivalent influenza vaccines instead of monovalent influenza vaccines.

Ontology-supported research on vaccine efficacy, safety and integrative biological networks

“…Different types of vaccines may also be associated with different vaccine adverse events (VAE) [17,18]. For example, many live attenuated vaccines are typically very efficient in stimulating protective immunity.…”

“…In addition, the relations between MedDRA terms are not or poorly defined. The poorly defined MedDRA hierarchical structure makes it difficult to use MedDRA for term clustering analysis [18]. The Systematized Nomenclature of Medicine (SNOMED) provides another commonly used terminology for general medical evaluation [25].…”

“…Two safety-related biomedical ontologies recently developed include: The Ontology of Adverse Events (OAE) [18,81] and the Ontology of Vaccine Adverse Events (OVAE) [82]. …”

“…Since the namespace AEO was taken by another ontology ( i.e. , “Anatomical Entity Ontology”), the name of AEO was later changed to OAE, which represents the “Ontology of Adverse Events” [18]. In addition, OAE differs from AEO in that the adverse events represented in OAE do not have to be causally induced by a medical intervention.…”

Computational vaccinology and the ICoVax 2012 workshop

“…Many EHR data are unstructured and thus require some kind of natural language processing (NLP) to dissect them into structured data. Ontological representation and modeling of EHR data can help better classification and analysis of the vaccine EHR data [50]. New statistical methods are needed to handle the high throughput EHR data.…”