Abstract
Anaplasma phagocytophilum is an emerging tick-borne pathogen causing human granulocytic anaplasmosis (HGA), tick-borne fever (TBF) in small ruminants, and other forms of anaplasmosis in different domestic and wild animals. The main vectors of this pathogen are Ixodes tick species, particularly I. scapularis in the United States and I. ricinus in Europe. One of the main limitations for the development of effective vaccines for the prevention and control of A. phagocytophilum infection and transmission is the identification of effective tick protective antigens. The objective of this study was to apply a vaccinomics approach to I. scapularis-A. phagocytophilum interactions for the identification and characterization of candidate tick protective antigens for the control of vector infestations and A. phagocytophilum infection. The vaccinomics pipeline included the use of quantitative transcriptomics and proteomics data from uninfected and A. phagocytophilum-infected I. scapularis ticks for the selection of candidate protective antigens based on the variation in tick mRNA and protein levels in response to infection, their putative biological function, and the effect of antibodies against these proteins on tick cell apoptosis and pathogen infection. The characterization of selected candidate tick protective antigens included the identification and characterization of I. ricinus homologs, functional characterization by different methodologies including RNA interference, immunofluorescence, gene expression profiling, and artificial tick feeding on rabbit antibodies against the recombinant antigens to select the candidates for vaccination trials. The vaccinomics pipeline developed in this study resulted in the identification of two candidate tick protective antigens that could be selected for future vaccination trials. The results showed that I. scapularis lipocalin (ISCW005600) and lectin pathway inhibitor (AAY66632) and I. ricinus homologs constitute candidate protective antigens for the control of vector infestations and A. phagocytophilum infection. Both antigens are involved in the tick evasion of host defense response and pathogen infection and transmission, but targeting different immune response pathways. The vaccinomics pipeline proposed here could be used to continue the identification and characterization of candidate tick protective antigens for the development of effective vaccines for the prevention and control of HGA, TBF, and other forms of anaplasmosis caused by A. phagocytophilum.
Highlights
IntroductionThe intracellular bacterium, Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) is an emerging tick-borne pathogen causing human granulocytic anaplasmosis (HGA), which has emerged as a tick-borne disease of humans in the United States, Europe and Asia, and tick-borne fever (TBF) in small ruminants, most notably in sheep in Europe (Gordon et al, 1932; Foggie, 1951; Dumler et al, 2001; Stuen et al, 2013; Bakken and Dumler, 2015; Dugat et al, 2015; Severo et al, 2015)
The results showed that I. scapularis ISCW005600 and AAY66632 and I. ricinus homologs constitute candidate protective antigens for the control of vector infestations and A. phagocytophilum infection
The vaccinomics pipeline included the use of quantitative transcriptomics and proteomics data from uninfected and A. phagocytophilum-infected I. scapularis ticks (Ayllón et al, 2015) for the selection of candidate protective antigens based on the variation in tick mRNA and protein levels in response to infection, their putative biological function, and the effect of antibodies against these proteins on tick cell apoptosis and pathogen infection (Figure 1)
Summary
The intracellular bacterium, Anaplasma phagocytophilum (Rickettsiales: Anaplasmataceae) is an emerging tick-borne pathogen causing human granulocytic anaplasmosis (HGA), which has emerged as a tick-borne disease of humans in the United States, Europe and Asia, and tick-borne fever (TBF) in small ruminants, most notably in sheep in Europe (Gordon et al, 1932; Foggie, 1951; Dumler et al, 2001; Stuen et al, 2013; Bakken and Dumler, 2015; Dugat et al, 2015; Severo et al, 2015). Vaccinomics is a holistic approach based on the use of genome-scale or omics technologies integrated in a systems biology approach to characterize tick-host-pathogen interactions for the development of next-generation vaccines (de la Fuente and Merino, 2013; Contreras et al, 2016; de la Fuente et al, 2016a; Villar et al, 2017). Basic biological information on tick-host-pathogen interactions translates into the identification and subsequent evaluation of new candidate protective antigens (de la Fuente and Merino, 2013; de la Fuente et al, 2016a; Villar et al, 2017)
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