Blood transcriptome profile induced by an efficacious vaccine formulated with salivary antigens from cattle ticks

• Published in: npj vaccines Vol. 4; no. 1; p. 53
• Main Authors: Maruyama, Sandra R., Carvalho, Benilton, González-Porta, Mar, Rung, Johan, Brazma, Alvis, Gustavo Gardinassi, Luiz, Ferreira, Beatriz R., Banin, Tamy M., Veríssimo, Cecília J., Katiki, Luciana M., de Miranda-Santos, Isabel K. F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.12.2019; Nature Publishing Group
• Subjects: 631/250/590/2294; 631/61/24/590/2294; 692/53/2423; Antigens; Arachnids; Biomedical and Life Sciences; Biomedicine; Cattle; Cell adhesion & migration; Cell cycle; Dendritic cells; Gene expression; Immunoglobulins; Infectious Diseases; Medical Microbiology; Medical research; Public Health; Vaccine; Vaccines; Virology; Protein vaccines; Predictive markers
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-019-0145-1

Ticks cause massive damage to livestock and vaccines are one sustainable alternative for the acaricide poisons currently heavily used to control infestations. An experimental vaccine adjuvanted with alum and composed by four recombinant salivary antigens mined with reverse vaccinology from a transcriptome of salivary glands from Rhipicephalus microplus ticks was previously shown to present an overall efficacy of 73.2% and cause a significant decrease of tick loads in artificially tick-infested, immunized heifers; this decrease was accompanied by increased levels of antigen-specific IgG1 and IgG2 antibodies, which were boosted during a challenge infestation. In order to gain insights into the systemic effects induced by the vaccine and by the tick challenge we now report the gene expression profile of these hosts’ whole-blood leukocytes with RNA-seq followed by functional analyses. These analyses show that vaccination induced unique responses to infestations; genes upregulated in the comparisons were enriched for processes associated with chemotaxis, cell adhesion, T-cell responses and wound repair. Blood transcriptional modules were enriched for activation of dendritic cells, cell cycle, phosphatidylinositol signaling, and platelets. Together, the results indicate that by neutralizing the tick’s salivary mediators of parasitism with vaccine-induced antibodies, the bovine host is able to mount normal homeostatic responses that hinder tick attachment and haematophagy and that the tick otherwise suppresses with its saliva. Tick vaccines: multivalent formulation activates leukocytes systemically Available vaccines to protect against the bovine tick Rhipicephalus microplus have variable efficacy, but a new experimental vaccine formulation featuring four R. microplus saliva antigens has shown enhanced protection against tick infestation by triggering the production of antigen-specific IgG antibodies in vaccinated bovines. Now, Isabel de Miranda-Santos and colleagues performed RNA sequencing analysis of peripheral blood immune cells from vaccinated calves and show that this multivalent vaccine induces systemic activation of leukocytes that prevents effective attachment of R. microplus ticks. The researchers report an increase in the expression of genes associated with chemotaxis, cell adhesion, T-cell responses and wound repair, and find evidence of enhanced activation of dendritic cells and platelets. The genes and biological pathways identified underline the importance of using vaccines to neutralize tick saliva, freeing systemic immune responses and skin immunity to prevent tick infestation in farm animals.