Ticks and tick-borne diseases are a growing burden worldwide and vaccines are effective control interventions. Vaccine formulations with tick antigens such as BM86/BM95 (BM) and Subolesin (SUB) have shown reduction in tick fitness and infestation in immunized hosts. However, antigen combination is a challenging approach to improve vaccine efficacy (E) against multiple tick species. Herein, in silico and in music algorithms were integrated to model BM-SUB protein-protein interactions to apply a quantum vaccinology approach for combining protective epitopes or immunological quantum in the chimeric antigen Q38-95. Cattle immunized with Q38-95 and infested with African blue tick Rhipicephalus decoloratus showed an 82% E similar to BM86 and higher than SUB. The immune mechanisms activated in cattle in response to vaccination with Q38-95 were mediated by anti-BM/SUB antibodies that interfered with BM-SUB interactions and through activation of other innate and adaptive immune pathways. The results support modelling protein-protein interactions affecting E to identify and combine candidate protective epitopes in chimeric antigens.

• MeSH
• Antigens * immunology   chemistry   MeSH
• Epitopes * immunology   chemistry   MeSH
• Tick Infestations * prevention & control   immunology   veterinary   MeSH
• Rhipicephalus immunology   MeSH
• Cattle MeSH
• Vaccines * immunology   MeSH
• Animals MeSH
• Check Tag
• Cattle MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antigens * MeSH
• Epitopes * MeSH
• Vaccines * MeSH

Epigenetic mechanisms have not been characterized in ticks despite their importance as vectors of human and animal diseases worldwide. Our investigation identifies and functionally characterizes the orthologue of S-adenosylmethionine (SAM) binding methyltransferase enzyme, disruptor of telomeric silencing 1-like (DOT1L) in Ornithodoros moubata (OmDOT1L), a soft tick vector for the relapsing fever pathogen Borrelia duttonii and the African swine fever virus. The OmDOT1L tertiary structure was predicted and compared to the Homo sapiens DOT1L which had been co-crystalized with SGC0946, a DOT1L-specific inhibitor. The amino acid residues crucial for SAM and SGC0946 binding conserved in most DOT1L sequences available, are also conserved in OmDOT1L. Quantitative PCR of Omdot1l during O. moubata life stages showed that transcripts were significantly upregulated in first-stage nymphs. O. moubata larvae exposed to SGC0946 displayed high mortality during molting to first-stage nymphs. Furthermore, a significant decrease in weight was observed in second-stage nymphs fed on recombinant OmDOT1L-immunized rabbits. In contrast, artificial blood feeding supplemented with SGC0946 did not affect survival and reproductive performance of adult female ticks. We concluded that OmDOT1L plays an essential role in the regulation of larval molting and the feeding of O. moubata second-stage nymphs.

• Keywords
• DOT1L, Ornithodoros moubata, histone methyltransferase,
• Publication type
• Journal Article MeSH

The main objective of this study was to propose a novel methodology to approach challenges in molecular biology. Akirin/Subolesin (AKR/SUB) are vaccine protective antigens and are a model for the study of the interactome due to its conserved function in the regulation of different biological processes such as immunity and development throughout the metazoan. Herein, three visual artists and a music professor collaborated with scientists for the functional characterization of the AKR2 interactome in the regulation of the NF-κB pathway in human placenta cells. The results served as a methodological proof-of-concept to advance this research area. The results showed new perspectives on unexplored characteristics of AKR2 with functional implications. These results included protein dimerization, the physical interactions with different proteins simultaneously to regulate various biological processes defined by cell type-specific AKR-protein interactions, and how these interactions positively or negatively regulate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in a biological context-dependent manner. These results suggested that AKR2-interacting proteins might constitute suitable secondary transcription factors for cell- and stimulus-specific regulation of NF-κB. Musical perspective supported AKR/SUB evolutionary conservation in different species and provided new mechanistic insights into the AKR2 interactome. The combined scientific and artistic perspectives resulted in a multidisciplinary approach, advancing our knowledge on AKR/SUB interactome, and provided new insights into the function of AKR2-protein interactions in the regulation of the NF-κB pathway. Additionally, herein we proposed an algorithm for quantum vaccinomics by focusing on the model proteins AKR/SUB.

• Keywords
• NF-κB, akirin, art, evolution, interactome, music, protective epitope, quantum vaccinomics, subolesin, vaccine, yeast two-hybrid,
• Publication type
• Journal Article MeSH