Abstract
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.
Highlights
Blood-feeding parasites act as vectors of an enormous range of pathogens that cause diseases in humans and other animals
Comparison of immunization with either 64TRP antigens, a commercial tick-borne encephalitis virus (TBEV) vaccine, or the commercial anti-tick vaccine (TickGARD) on (A) transmission 1⁄4 % uninfected nymphal ticks that became infected; (B) support 1⁄4 % mice supporting cofeeding virus transmission between an infected adult female tick and uninfected nymphs; and (C) survival 1⁄4 % mice that survived an infected tick bite
In the mouse model for tick-borne transmission of TBEV, the virus is transmitted from an infected tick to the uninfected mouse on which it feeds
Summary
Blood-feeding parasites act as vectors of an enormous range of pathogens that cause diseases in humans and other animals. A single tick species (Ixodes ricinus) can transmit viruses, bacteria, and protozoa that cause tick-borne encephalitis, Lyme disease, and babesiosis. A novel approach is antivector vaccines designed to target the vector in such a way that they protect against pathogens transmitted by the vector. Several observations suggest this may be feasible. Reduced transmission capacity of ticks fed on tick-immune animals [1,2,3,4,5] and humans [6] has been reported for several tick-borne pathogens, not all [7]. It has been shown that antibodies raised against mosquito midgut lysates lowered vector competence, reducing transmission of human malarial parasites [10], while antibodies to a sandfly midgut galectin eliminated sandfly transmissible infections of leishmania [11] in membrane feeding studies
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