Mouse disease model for evaluation of prophylactic and therapeutic treatments of
Compositions and methods are provided for evaluating the progress of disease induced by infection with Chlamydia spp. Specifically, the invention provides a mouse lung disease model of infection with Chlamydia spp. bacteria. The compositions and methods of the invention find use in evaluating the efficacy of vaccines and other therapeutic or prophylactic treatments of Chlamydia -induced disease.
1. A method of evaluating the efficacy of a therapeutic or prophylactic treatment of Chlamydia -induced disease, comprising the steps of:
a) rationally selecting a particular mouse strain and identifying whether said strain is a low nitric oxide (NO) responder strain or a high NO responder strain when said strain is exposed to bacterial antigens;
b) rationally selecting a dose of Chlamydia to be administered to a test mouse of said strain;
c) if said mouse strain is a low nitric oxide responder, rationally selecting a feeding regimen with high levels of arginine and feeding said test mouse according to said regimen, and if said mouse strain is a high nitric oxide responder, performing at least one step selected from the group consisting of:
(i) rationally selecting a feeding regimen with low levels of arginine and feeding said test mouse according to said regimen; and
(ii) treating said test mouse with an inhibitor of nitric oxide synthase-2 (NOS2);
d) administering said dose of Chlamydia to said test mouse;
e) administering said therapeutic or prophylactic treatment to said test mouse; and
f) assessing the severity of chlamydial disease in said test mouse.
2. The method of claim 1 , wherein said treatment is a prophylactic treatment and said step of administering said prophylactic treatment is performed before said step of administering Chlamydia to said mouse.
3. The method of claim 1 , wherein the step of administering Chlamydia to said mouse comprises administering between 1×10 5 and 1×10 6 IFU of Chlamydia to said mouse intranasally.
4. The method of claim 1 , wherein said mouse strain is A/J.
5. The method of claim 4 , wherein the step of rationally selecting a feeding regimen comprises selecting a diet high in protein and arginine.
6. The method of claim 1 , wherein the step of rationally selecting a dose of Chlamydia to be administered to said test mouse comprises evaluating the mouse strain from which said test mouse is selected to determine the LD 50 for said mouse strain when treated with Chlamydia psittaci.