Laboratório de Imunologia e Microbiologia, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.
Vet Parasitol. 2021 Dec;300:109610. doi: 10.1016/j.vetpar.2021.109610. Epub 2021 Oct 29.
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.
蜱虫对全球人类健康和畜牧业构成重大威胁，每年造成的经济损失超过数十亿美元。这种情况促使人们开发针对这些外寄生虫的疫苗，而控制蜱虫的主要方法仍然依赖于使用杀蜱剂，这不仅增加了成本，还可能影响环境以及人类和动物的健康。针对蜱虫 Rhipicephalus microplus 生产的第一批商业疫苗是基于抗体的。为了产生针对蜱虫的保护性免疫反应，人们进行了许多额外的尝试，通过使用特定抗原进行免疫接种，而抗体反应通常是评估的主要目标。但是，一些争议仍然存在于体液反应在蜱-哺乳动物宿主关系中可能发挥的作用。本文重点分析了与抗体和蜱虫有关的具体方面，特别是寄生虫密度和逃避/调节的影响。还编译和分析了已经针对 R. microplus 进行的免疫试验，根据测试分子、免疫接种方案和蜱虫挑战的特点进行分析。在这些问题中，讨论了抗体水平是否可以直接与蜱虫抗性的发展相关，以及在不同蜱虫密度下，由寄生虫感染产生的抗蜱虫保护性免疫反应是否可能变得无效。此外，更高的抗体滴度可以与对蜱虫感染的保护或易感性相关，而这可能在连续或重复感染后发生改变，并且在具有不同遗传背景的宿主之间存在很大差异。关于逃避机制，蜱虫具有一种复杂的机制来处理抗体，包括免疫球蛋白结合蛋白（IGBPs），这些蛋白可以捕获、运输和将抗体重新注入宿主，同时保持其在寄生虫中的特性。免疫接种方案的比较显示，已经有 22 种分子在针对 R. microplus 的牛疫苗接种试验中进行了测试，其中隐蔽和双重抗原占主导地位，并且蜱虫挑战方案存在明显差异。当面临不同寄生虫密度时，存在抗体逃避机制和蜱虫抗性的变化，这是在测试候选疫苗时应考虑的问题。最终，可能需要更精细的设计来有效地设计针对蜱虫分子的鸡尾酒疫苗，这些疫苗可能需要在非竞争免疫环境中进行改变和组合，以实现普遍的安全性和保护效果。
