Identification of vaccine candidates for the control of dermanyssus gallinae: a one health issue

The hematophagous mite, Dermanyssus gallinae, also known as the Poultry Red Mite (PRM) is the major pest for the egg-laying industry worldwide. It is associated with severe economic loses and means a serious threat for the hen health and welfare. In addition, the mite can feed on humans causing a skin condition known as gamasoidosis. Traditional control methods against the PRM are based on spraying with synthetic acaricides. The lack of effectivity and the development of resistances imply the need for alternative control methods. The present thesis is framed in the One Health approach, focused in the assessment of the zoonotic risk of D. gallinae and in the identification, through omics tools, of vaccine candidates for the alternative control of PRM infestations. Chapter I: General Introduction Chapter I. This chapter provides a general overview of the current research on control methods against PRM infestations. It is also a compilation of the most recent advances in the biology of the mite, the harms to the laying-egg industry and the impact to the environment and human health. A special attention has been paid to the novelties in the vaccine development that has been enhanced with the recent characterization of the mite genome and proteome. [Lima-Barbero, J.F., Höfle, U., Villar, M. & de la Fuente, J. (2019) Challenges for the control of the Poultry Red Mite (Dermanyssus gallinae) in Parasitology and Microbiology Research. Submitted]. Chapter II: Gamasoidosis: human response to avian mite infestations. Chapter IIa. This chapter is a report of a clinical gamasoidosis caused by Ornithonyssus bursa. This is the first report of O. bursa, a tropical mite which is recently expanding across Europe, affecting humans in Spain. In addition, this work demonstrated the absence of ?-Gal in D. gallinae and the lack of clear human response to the mite bites. [Lima-Barbero, J. F.; Sánchez-Sánchez, M.; Cabezas-Cruz, A.; Mateos-Hernández, L.; Contreras, M.; Fernández de Mera, I. G.; Villar, M.; de la Fuente, J. (2019) Clinical gamasoidosis and antibody response in two patients infested with Ornithonyssus bursa (Acari: Gamasida: Macronyssidae). Experimental and Applied Acarology, 78 (4): 555-564] Chapter IIb. This chapter is a description of two clinical cases of gamasoidosis in two workers from the same laying egg farm. D. gallinae was identified by SEM microscopy as the responsible for the dermatitis. In this work the onset of the signs is also associated with a status of severe infestation in the hen house and a close contact with large number of mites while an absence of a clear immune response was observed. [ Lima-Barbero, J. F.; Temple, D.; Prado, E.; Villar, M. & de la Fuente, J. (2019) Gamasoidosis in two workers related to the poultry industry. Medical and Veterinary Entomology. Submitted] Chapter III: Omics approach for improving the knowledge about D. gallinae and the identification of vaccines candidates. Chapter IIIa. In this chapter a vaccinology approach was followed to identify potential vaccines candidates for the control of D. gallinae. Firstly, we characterized the proteome for fed and unfed nymphs and adults. Amongst those proteins that showed different level of expression we selected Calumenin (Deg-CALU) to be evaluated as vaccine candidate. By an on-hen feeding trial where we tested Deg-CALU and Rhm- SUB, as a positive control. The vaccination with Deg-CALU and Rhm-SUB reduced the mite oviposition by a 35 and 44%, respectively. These results supports the consideration of Deg-CALU and Rhm-SUBO as suitable vaccine candidates for the control of PRM infestation [Lima-Barbero, J. F.; Contreras, M.; Mateos-Hernández, L.; Mata-Lorenzo, F. M.; Triguero-Ocaña, R.; Sparagano, O.; Finn, R. D.; Strube, C.; Price, D. R. G.; Nunn, F.; Bartley, K.; Höfle, U.; Boadella, M.; Nisbet, A. J.; de la Fuente, J. & Villar, M. (2019) A vaccinology approach to the identification and characterization of Dermanyssus gallinae candidate protective antigens for the control of poultry red mite infestations. Vaccines. Submitted] Chapter IIIb. Based on the protective effects of the akirin/subolesin vaccines for the control of ectoparasites infestations, the akirin gene for D. gallinae (Deg-akr) was identified and the effectivity of recombinant Deg-AKR vaccines evaluated. An on-hen feeding assay was performed to evaluate the effects on the vaccination with Deg-AKR against PRM infestations. The vaccination induced an effective immune response in the hens that reduced the mite oviposition by a 42% supporting the use of Deg-AKR as a candidate protective antigen aga for the control of PRM population growth. [Lima- Barbero, J. F.; Contreras, M.; Bartley, K.; Price, D. R. G.; Nunn, F.; Sánchez-Sánchez, M.; Prado, E.; Höfle, U.; Villar, M.; Nisbet, A. J. & de la Fuente, J. (2019) Reduction in Oviposition of Poultry Red Mite (Dermanyssus gallinae) in Hens Vaccinated with Recombinant Akirin. Vaccines 7 (3): 121] Chapter IIIc. This chapter means a contribution to the knowledge of the PRM microbiome focussing on the alphaproteobacteria taxonomic Class. Following a metaproteomic approach the bacterial communities for fed and unfed nymphs and adult mites were characterized. The bacterial community has, mainly, an environmental source but potential pathogenic and symbiotic bacteria were identified. [Lima-Barbero, J. F.; Díaz-Sanchez, S.; Sparagano, O.; Finn, R. D.; de la Fuente, J. & Villar, M. (2019) Metaproteomics characterization of the alphaproteobacteria microbiome in different developmental and feeding stages of the poultry red mite Dermanyssus gallinae (De Geer, 1778). Avian Pathology 48: S52-S59]