Ontological representation, modeling, and analysis of parasite vaccines

Background: Pathogenic parasites are responsible for multiple diseases, such as malaria and Chagas disease, in humans and livestock. Traditionally, pathogenic parasites have been largely an evasive topic for vaccine design, with most successful vaccines only emerging recently. To aid vaccine design, the VIOLIN vaccine knowledgebase has collected vaccines from all sources to serve as a comprehensive vaccine knowledgebase. VIOLIN utilizes the Vaccine Ontology (VO) to standardize the modeling of vaccine data. VO did not model complex life cycles as seen in parasites. With the inclusion of successful parasite vaccines, an update in parasite vaccine modeling was needed.

Results: VIOLIN was expanded to include 258 parasite vaccines against 23 protozoan species, and 607 new parasite vaccine-related terms were added to VO since 2022. The updated VO design for parasite vaccines accounts for parasite life stages and for transmission-blocking vaccines. A total of 356 terms from the Ontology of Parasite Lifecycle (OPL) were imported to VO to help represent the effect of different parasite life stages. A new VO class term, 'transmission-blocking vaccine,' was added to represent vaccines able to block infectious transmission, and one new VO object property, 'blocks transmission of pathogen via vaccine,' was added to link vaccine and pathogen in which the vaccine blocks the transmission of the pathogen. Additionally, our Gene Set Enrichment Analysis (GSEA) of 140 parasite antigens used in the parasitic vaccines identified enriched features. For example, significant patterns, such as signal, plasma membrane, and entry into host, were found in the antigens of the vaccines against two parasite species: Plasmodium falciparum and Toxoplasma gondii. The analysis found 18 out of the 140 parasite antigens involved with the malaria disease process. Moreover, a majority (15 out of 54) of P. falciparum parasite antigens are localized in the cell membrane. T. gondii antigens, in contrast, have a majority (19/24) of their proteins related to signaling pathways. The antigen-enriched patterns align with the life cycle stage patterns identified in our ontological parasite vaccine modeling.

Conclusions: The updated VO modeling and GSEA analysis capture the influence of the complex parasite life cycles and their associated antigens on vaccine development.