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

Sandra R Maruyama,Beatriz R Ferreira,Isabel K F De Miranda-Santos,Benilton Carvalho,Alvis Brazma,Cecília J Veríssimo,Luciana M Katiki,Mar González-Porta,Luiz Gustavo Gardinassi,Tamy M Banin,Johan Rung

doi:10.1038/s41541-019-0145-1

Abstract

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.

Highlights

Rhipicephalus microplus, the cattle tick, causes heavy infestations in taurine breeds of cattle, severely affecting their health and causing huge production losses where they are employed.[1]
Blood samples from that experiment were employed in this study to perform RNA-seq analysis; 24 blood samples were collected from calves in the control and vaccinated groups (n = 4 in each group) at three different time points: before vaccination (BA, adjuvant only group; BV, vaccinated group), on day 7 after the third and last vaccine dose (AA, adjuvant only group; after vaccination (AV), vaccinated group) and on day 17 after a challenge with tick
Seq experiment were collected before vaccination (BV) or administration of control adjuvant (BA), after vaccination (AV) or administration of control adjuvant (AA), and after challenge tick infestation in vaccinated (CHV) and control adjuvant (CHA) animals

Summary

Introduction

Rhipicephalus microplus, the cattle tick, causes heavy infestations in taurine breeds of cattle, severely affecting their health and causing huge production losses where they are employed.[1]. TickGard[2] and GAVAC3 are the vaccines to control cattle ticks that went to market Both are based on a single antigen, the tick gut glycoprotein Bm86. An approach to obtain a level of vaccine efficacy compatible with ease of management and good production in the field consists of formulating a multicomponent vaccine combining many antigens, in an attempt to decrease the proportion of poor responders to the vaccine and to target the tick’s multiple mediators of parasitism Since these mediators are mostly in the saliva that ticks inoculate in their hosts, memory may be boosted when cattle are naturally exposed to ticks

Methods

Results

Conclusion