Chlamydiae are atypical intracellular bacteria that infect via mucosal surfaces causing, for example, trachoma, pneumonia, cervicitis, urethritis and infertility. Existing antibiotics are only partially effective and no vaccines are available. Using surface expressed or secreted proteins previously identified by genomics and proteomics we tested five as vaccines against intranasal challenge with Chlamydia pneumoniae. One antigen, LcrE, induced CD4+ and CD8+ T cell activation, type 1 cytokine secretion and neutralising antibodies and was completely effective in eliminating infection. Such antigens are highly conserved and essential to all Chlamydial species. The discovery of an effective vaccine for Chlamydiae pneumoniae has potential wide benefits for human health.