Ticks and antibodies: May parasite density and tick evasion influence the outcomes following immunization protocols?

Ticks are a major concern to human health and livestock worldwide, being responsible for economic losses that go beyond billions of US dollars per year. This scenario instigates the development of vaccines against these ectoparasites, emphasized by the fact that the main method of controlling ticks still relies on the use of acaricides, what increases costs and may affect the environment as well as human and animal health. The first commercial vaccines against ectoparasites were produced against the tick Rhipicephalus microplus and their efficacy were based on antibodies. Many additional attempts have been conducted to produce protective immune responses against ticks by immunization with specific antigens and the antibody response has usually been the main target of evaluation. But some controversy still populates the roles possibly performed by humoral responses in tick-mammalian host relationships. This review focuses on the analysis of specific aspects concerning antibodies and ticks, especially the influence of parasite density and evasion/modulation. The immunization trials already described against R. microplus were also compiled and analyzed based on the characteristics of the molecules tested, protocols of immunization and tick challenge. Within these issues, it is discussed if or when antibody levels can be directly correlated with the development of tick resistance, and whether anti-tick protective immune responses generated by infestations may become ineffective under a different tick density. Also, higher titers of antibodies can be correlated with protection or susceptibility to tick infestations, what may be altered following continuous or repeated infestations and differ greatly comparing hosts with distinct genetic backgrounds. Regarding evasion, ticks present a sophisticated mechanism for dealing with antibodies, including Immunoglobulin Binding Proteins (IGBPs), that capture, transport and inject them back into the host, while keeping their properties within the parasite. The comparison of immunization protocols shows a total of 22 molecules already tested in cattle vaccination trials against R. microplus, with the predominance of concealed and dual antigens as well as marked differences in tick challenge schemes. The presence of an antibody evasion apparatus and variable levels of tick resistance when facing different densities of parasites are concerns that should be considered when testing vaccine candidates. Ultimately, more refinement may be necessary to effectively design a cocktail vaccine with tick molecules, which may be needed to be altered and combined in non-competing immune contexts to be universally secure and protective.