Chlamydia is the most common bacterial STI, with 131 million new infections annually, affecting both females and males equally. Many infections are asymptomatic and go undiagnosed and untreated. Our recent studies in mice (1-4) and men (5) suggest male chlamydial infection adversely impacts spermatogenesis. In mice, chlamydia is rapidly transported from the urethra to the testes in macrophages where Sertoli cells, Leydig cells and testicular macrophages are all infected. Infection causes decreased sperm motility, decreased zona-binding, global DNA hypomethylation and increased DNA damage, and adversely affects offspring development of infected sires. In infertile men we also detected Chlamydia infection in 45% of patients attending infertility clinics.
Using our male mouse model of C. muridarum infection we evaluated the effectiveness of intranasal vaccination with chlamydial major outer membrane protein, combined with ISCOMATRIX adjuvant to protect against sperm damage. Prophylactic vaccination protected against infection-induced impairment of sperm motility, morphology, oocyte-binding, and DNA damage and significantly reduced and, in some cases, cleared chlamydial burden from the testes, prostates and epididymides. Therapeutic vaccination, initiated after the establishment of infection also reduced the chlamydial burden in the testes, prostates and epididymides and provided partial protection against sperm DNA damage and abnormal sperm morphology.
Vaccine-mediated protection was not associated with classical interferon-secreting Th1 cells, which protect female mice against infection, but rather a combination of multifunctional CD4/8+ T cells in both the lower reproductive tract and testes, combined with local and systemic IgG and IgA production. These T cells included cells with a regulatory phenotype (Trem), suggesting that protective immune mechanisms must operate in concert with protection of the immune privilege in the testes to maintain successful spermatogenesis.