The major outer membrane protein (MOMP) of Chlamydia pneumoniae is a 40 kDa porin and represents approximately 60% of the outer membrane protein pool. Previous studies have shown that MOMP can dampen down T-cell-mediated immune responses. We decided to assess if this effect could have an impact on atherosclerotic plaque development. We used recombinant Mycobacterium vaccae (M vaccae) vectors expressing MOMP (with and without signal sequence) to vaccinate ApoE−/− mice intranasally. Animals received one initial dose and two booster doses 3 weeks apart and continued with a standard Chow diet for another 4 weeks. Control mice received phosphate-buffered saline or were left untreated. Plasma collected before immunisation and at termination was used to measure levels of interferon γ, interleukin (IL)-4 and IL-10 and also IgG1 and IgG2b. Atherosclerotic plaque development was assessed using paraffin sections of the brachiocephalic artery. Our results show that intranasal administration of M vaccae vectors expressing MOMP, with or without signal sequence, promotes anti-atherogenic T-cell responses and halts the development and progression of atherosclerotic plaques in ApoE−/− mice.