Liposome Delivery of Chlamydia muridarum Major Outer Membrane Protein Primes a Th1 Response That Protects against Genital Chlamydial Infection in a Mouse Model1

摘要

Background.Immunity to chlamydia is thought to rely on interferon (IFN)–γ–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.nnMethods.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 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.nnResults.Mice vaccinated with MOMP/alum displayed a strong anti‐MOMP humoral response with high IgG1 titers, low levels of IFN‐γ and tumor necrosis factor (TNF)–α, and only a slight reduction in chlamydial load. Mice vaccinated with MOMP/CAF01 displayed high titers of IgG2b, IFN‐γ, and TNF‐α 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.nnConclusion.CAF01 adjuvant facilitates a protective anti‐MOMP CD4+ T cell response independent of MOMP conformation.