The uninfected Ixodes scapularis human tick challenge model

The incidence of tick-borne diseases (TBDs) has rapidly increased in the last
past decades leading to an increasing health problem in the Northern
hemisphere. Currently there are few effective ways of preventing someone from
getting a tick-borne disease, although studies have shown vaccination to be a
cost-effective way of prevention. An innovative way to prevent multiple
tick-borne diseases is an anti-tick vaccine, i.e. targeting the vector to
prevent transmission of pathogens from the tick to the host. The rationale for
an anti-tick vaccine stems from a phenomenon coined tick immunity. After
repeated tick feeding non-natural hosts develop innate and adaptive immune
responses against tick antigens. Subsequent tick feeding is impaired, which
leads to (partial) protection against Lyme disease and other tick-borne
diseases. Of interest, there is anecdotal evidence that ticks die after feeding
on individuals that were previously highly exposed to tick-bite (i.e. tick
biologists). Also, epidemiological studies have shown that humans, also
non-natural hosts, with a local rash and itch at the tick bite site are less
likely to become infected with Borrelia burgdorferi. Finally, we also have
unpublished preliminary experimental evidence that tick immunity might exist in
humans.

To show proof of concept that humans indeed develop immunity to ticks.

This will be an, single centre, experimental study. The design of the study is
similar to a human challenge trial, with the important exception that the
subjects in this study are not experimentally infected with a pathogen, but are
exposed to well-characterized laboratory-reared uninfected nymphal Ixodes
scapularis ticks.

We will challenge the subjects three to four times with ticks reared in colony
from a designated laboratory and that are exhaustively tested negative for
various tick-borne pathogens. We will evaluate several tick feeding parameters
to assess the development of tick immunity in the subjects. To this end, a
total amount of ten ticks per challenge will be placed under a dressing placed
on the arm.

Subjects will undergo three to four tick challenges, consisting of five to six
days per challenge with two weeks between the consecutive challenges. The total
duration of participation is approximately five months for each subject (of
which the last two and a half month only consists of one venipuncture at the
end). During the study 345-413ml of blood will be drawn. At the end of the last
challenge, two or three skin biopsies are taken from the tick bite site (and
optional 1 biopsy after the first challenge). By making use of ticks from a
laboratory-reared tick colony that have been, and are being, used in
xenodiagnosis and tick challenge models in the USA and that are well tolerated
we ensure that the tick challenges are safe. Regardless, the tick challenge can
cause some discomfort because of possible local reactions and because the
dressing must be kept dry for five to six days. The risk of infection with a
tick-borne pathogen is negligible due to the fact that these ticks are
exhaustively tested for various tick-borne pathogens. Finally, we also consider
the risk of development of a red meat allergy or other allergic reactions
negligible because no clear associations are known of I. scapularis ticks and
red meat allergy. No serious adverse events (such as human infections or red
meat allergy) have resulted from more than >100 challenges in the United States
using this tick colony. There are no direct benefits of participation.