Q-VaxCelerate: Development of a T Cell-Based Vaccine for Q Fever

Coxiella burnetii is a highly infectious and stable pathogen that can cause
acute and severe chronic Q fever in humans. Q fever outbreaks have occurred in
Australia and the Netherlands and have been of concern to the Department of
Defense (USA). Although C. burnetii infection can be treated with antibiotics,
a vaccine is considered to be critical to control this disease. There is a
clear mandate and a medical need to develop an efficacious and less reactogenic
vaccine for occupational and biodefense purposes, which is addressed by our
proposal. As CD4+ T cell immunity plays a much more critical role in protective
immunity against the pathogen than antibodies, the Q-VaxCelerate proposal sets
out to develop a T-cell based Q fever vaccine candidate. Innatoss has developed
a T cell based Q fever test, that will be used to identify protective T cell
epitopes in humans that have been exposed to Cb.

Identification of T cell epitopes that will serve as the basis for a novel Q
fever vaccine with fewer side effects. This will be done by determining ex vivo
the effect of Cb-derived T cell epitopes on IFN-γ production in blood of
healthy volunteers, subjects with active or resolved Q fever infection (acute
or chronic), and subjects previously vaccinated with Q-VAX. All participants
will be HLA-typed and T cell responses and antibody formation will be
characterized prior to testing selected peptides.
In addition, comparison of T cell responses in subject with and without acute
disease will be done for biomarker discovery to differentiate protective,
non-protective and reactogenic epitopes. Also, the role of anti-Coxiella
antibody formation on T cell responses will be determined.

T cell responses will be determined in former acute Q fever patients, subjects
exposed to Cb who did not develop disease, healthy controls, chronic Q fever
patients, and vaccinees. In a selection of volunteers with good T cell
responses, cell markers and cytokines in response to Cb will be investigated
using different technologies in search of markers for non-protective,
protective and reactogenic responses. Subsequently, blood samples from these
subjects will be used to screen up 200 potential protective T cell epitopes.

The risks associated with standard blood drawing are negligible. Blood drawing
posts will assist participants and when needed, in particular during the
intake, an Innatoss employee will be present to coordinate blood drawing and
assist participants.
Risks associated with testing for Q fever are that a control subject may be
positive in Q-detect indicating recent exposure to C. burnetii since all
subjects were tested previously. If results during the study suggest possible
acute or chronic Q fever, a microbiologist will be consulted and subjects and
their GP will be informed. Considering the consequence of lack of treatment, it
is not possible to participate without consent on this point.
This research can only be done with blood of coxiella exposed (or vaccinated)
subjects, as only these people have Cb and Cb derived peptide specific T cel
responses. These responses are required to select for potentially protective T
cel epitopes to develop a Q fever vaccine.