Liposome delivery of Chlamydia muridarum major outer membrane protein primes a Th1 response that protects against genital chlamydial infection in a mouse model

Abstract

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. 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 × 105 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-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. Conclusion. CAF01 adjuvant facilitates a protective anti-MOMP CD4+ T cell response independent of MOMP conformation. © 2008 by the Infectious Diseases Society of America. All rights reserved.