An antivector vaccine protects against a lethal vector-borne pathogen.
An antivector vaccine protects against a lethal vector-borne pathogen.
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DOI：
10.1371/journal.ppat.0020027
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发表时间：
2006-04
期刊：
影响因子：
6.7
通讯作者：
Nuttall, Patricia A
中科院分区：
文献类型：
--
作者：
Labuda, Milan;Trimnell, Adama R;Lickova, Martina;Kazimirova, Maria;Davies, Gillian M;Lissina, Olga;Hails, Rosie S;Nuttall, Patricia A
针对吸血病媒（如蚊子和蜱虫）的疫苗有可能预防由病媒传播的病原体引起的许多疾病。我们测试了从尾尾棘头蜱黏结蛋白（64TRP）中提取的抗蜱疫苗保护小鼠免受受感染的蓖麻蜱传播的蜱传脑炎病毒（TBEV）的能力。该疫苗在免疫动物中具有“双重作用”：当蜱虫感染时，炎症和免疫反应首先破坏皮肤进食部位，导致血液进食受损，然后特异性抗64trp抗体与中肠抗原表位交叉反应，导致蜱虫中肠破裂和充血的蜱虫死亡。测量了三个参数：“传播”，即未感染的蜱虫若虫与受感染的成年雌蜱共食时被感染的数量；“支持”，支持病毒从受感染的蜱虫传播到未受感染的若虫的小鼠数量；“存活率”指的是被蜱虫叮咬感染后存活下来的小鼠数量，以及随后通过腹腔注射致死剂量的TBEV的小鼠数量。我们发现，一剂64TRP疫苗可以保护小鼠免受受感染蜱虫的致命攻击；对照动物患上了致命的病毒性脑炎。64TRP疫苗的保护作用与单剂TBEV疫苗相当，而在减少支持病毒传播的动物数量方面，64TRP的传播阻断作用优于抗病毒疫苗。相比之下，仅针对蜱虫中肠的商业抗蜱疫苗（TickGARD）显示出传播阻断活性，但没有保护作用。64TRP疫苗显示出通过干扰病原体传播来控制媒介传播疾病的潜力，显然是通过在蜱进食部位介导局部皮肤炎症免疫反应。蚊子和蜱虫等吸血媒介传播数百种微生物，导致疟疾和莱姆病等疾病。控制这么多疾病是一项巨大的挑战。一个新的想法是制造针对病媒的疫苗，而不是针对它们携带的所有单个疾病媒介的疫苗。作者用蜱虫水泥制备的疫苗检验了这一假设。这种黏合剂由蜱虫分泌，帮助它们附着在人类或动物身上进食。在小鼠模型中，小鼠感染了感染了蜱传脑炎病毒（TBEV）的蜱，这是欧洲和北亚最重要的媒介传播病毒。对照组小鼠在被感染蜱虫叮咬约一周后出现致命性脑炎死亡。相比之下，蜱虫水泥疫苗提供的保护水平与接种了一针商用TBEV疫苗的小鼠相似。然而，一种用于控制牛蜱的商业蜱疫苗并没有保护老鼠。作者的蜱虫水泥疫苗似乎通过在蜱虫进食的皮肤上引起细胞免疫反应而起作用。这些结果表明，生产一种针对蜱虫的疫苗是可行的，这种疫苗可以防止蜱虫传播的疾病。
Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks, have the potential to protect against the many diseases caused by vector-borne pathogens. We tested the ability of an anti-tick vaccine derived from a tick cement protein (64TRP) of Rhipicephalus appendiculatus to protect mice against tick-borne encephalitis virus (TBEV) transmitted by infected Ixodes ricinus ticks. The vaccine has a “dual action” in immunized animals: when infested with ticks, the inflammatory and immune responses first disrupt the skin feeding site, resulting in impaired blood feeding, and then specific anti-64TRP antibodies cross-react with midgut antigenic epitopes, causing rupture of the tick midgut and death of engorged ticks. Three parameters were measured: “transmission,” number of uninfected nymphal ticks that became infected when cofeeding with an infected adult female tick; “support,” number of mice supporting virus transmission from the infected tick to cofeeding uninfected nymphs; and “survival,” number of mice that survived infection by tick bite and subsequent challenge by intraperitoneal inoculation of a lethal dose of TBEV. We show that one dose of the 64TRP vaccine protects mice against lethal challenge by infected ticks; control animals developed a fatal viral encephalitis. The protective effect of the 64TRP vaccine was comparable to that of a single dose of a commercial TBEV vaccine, while the transmission-blocking effect of 64TRP was better than that of the antiviral vaccine in reducing the number of animals supporting virus transmission. By contrast, the commercial antitick vaccine (TickGARD) that targets only the tick's midgut showed transmission-blocking activity but was not protective. The 64TRP vaccine demonstrates the potential to control vector-borne disease by interfering with pathogen transmission, apparently by mediating a local cutaneous inflammatory immune response at the tick-feeding site. Blood-sucking vectors such as mosquitoes and ticks transmit hundreds of micro-organisms that cause diseases like malaria and Lyme disease. Controlling so many diseases is an enormous challenge. A new idea is to make vaccines against the vectors rather than against all the individual disease agents they carry. The authors examined this hypothesis using a vaccine prepared from tick cement. This cement is secreted by ticks to help them attach to a human or animal to feed. A mouse model was used in which mice were infested with ticks infected with tick-borne encephalitis virus (TBEV), the most important vector-borne virus in Europe and northern Asia. The control mice developed fatal encephalitis and died about a week after being bitten by the infected tick. By contrast, the tick cement vaccine gave protection similar to the level seen in mice immunized with a single shot of the commercial TBEV vaccine for humans. However, a commercial tick vaccine used to control cattle ticks did not protect the mice. The authors' tick cement vaccine appeared to work by causing a cellular immune response in the skin where ticks were feeding. These results show that it is feasible to produce a vaccine against a tick that protects against the disease agent it transmits.