Liposome delivery of Chlamydia muridarum major outer membrane protein primes a Th1 response that protects against genital chlamydial infection in a mouse model.
BACKGROUND
Immunity to chlamydia is thought to rely on interferon (IFN)-gamma-secreting T helper cells type 1 (Th1) with an additional effect of secreted antibodies. A need for Th1-polarizing adjuvants in experimental chlamydia vaccines has been demonstrated, and antigen conformation has also been reported as being important for raising protective immunity.


METHODS
C57BL/6 mice vaccinated with native refolded Chlamydia muridarum major outer membrane protein (MOMP) adjuvanted with either Th1-promoting cationic adjuvant formulation 1 (CAF01) or T helper cells type 2-promoting aluminum hydroxide (alum) received a genital inoculation of 1.5 x 10(5) inclusion-forming units of C. muridarum. The role played by CD4(+) T cells in MOMP/CAF01-raised immunity was investigated by depleting CD4(+) T cells in vaccinated mice, and antigen conformation dependence was evaluated by vaccination with recombinant MOMP.


RESULTS
Mice vaccinated with MOMP/alum displayed a strong anti-MOMP humoral response with high IgG1 titers, low levels of IFN-gamma and tumor necrosis factor (TNF)-alpha, and only a slight reduction in chlamydial load. Mice vaccinated with MOMP/CAF01 displayed high titers of IgG2b, IFN-gamma, and TNF-alpha and a profoundly reduced vaginal chlamydial load, compared with control mice. The protection was CD4(+) T cell dependent and was not dependent on MOMP conformation.


CONCLUSIONS
CAF01 adjuvant facilitates a protective anti-MOMP CD4(+) T cell response independent of MOMP conformation.
Hansen
Jon
J
Chlamydia and Adjuvant Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
Jensen
Klaus Thorleif
KT
Follmann
Frank
F
Agger
Else Marie
EM
Theisen
Michael
M
Andersen
Peter
P
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D012488:Salpingitis / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D014621:Vagina / Q000382:microbiology
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D007074:Immunoglobulin G; D008081:Liposomes