Immunization with a MOMP-Based Vaccine Protects Mice against a Pulmonary Chlamydia Challenge and Identifies a Disconnection between Infection and Pathology Connor P. O’Meara 1 , Charles W. Armitage 1 , Marina C. G. Harvie 1 , Peter Timms 1 , Nils Y. Lycke 2 , Kenneth W. Beagley 1 * 1 Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, Queensland, Australia, 2 Mucosal Immunobiology and Vaccine Centre (MIVAC), University of Go ¨ teborg, Go ¨ teborg, Go ¨ taland, Sweden Abstract Chlamydia pneumoniae is responsible for up to 20% of community acquired pneumonia and can exacerbate chronic inflammatory diseases. As the majority of infections are either mild or asymptomatic, a vaccine is recognized to have the greatest potential to reduce infection and disease prevalence. Using the C. muridarum mouse model of infection, we immunized animals via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, with recombinant chlamydial major outer membrane protein (MOMP) combined with adjuvants CTA1-DD or a combination of cholera toxin/CpG- oligodeoxynucleotide (CT/CpG). Vaccinated animals were challenged IN with C. muridarum and protection against infection and pathology was assessed. SL and TC immunization with MOMP and CT/CpG was the most protective, significantly reducing chlamydial burden in the lungs and preventing weight loss, which was similar to the protection induced by a previous live infection. Unlike a previous infection however, these vaccinations also provided almost complete protection against fibrotic scarring in the lungs. Protection against infection was associated with antigen-specific production of IFNc, TNFa and IL-17 by splenocytes, however, protection against both infection and pathology required the induction of a similar pro-inflammatory response in the respiratory tract draining lymph nodes. Interestingly, we also identified two contrasting vaccinations capable of preventing infection or pathology individually. Animals IN immunized with MOMP and either adjuvant were protected from infection, but not the pathology. Conversely, animals TC immunized with MOMP and CTA1-DD were protected from pathology, even though the chlamydial burden in this group was equivalent to the unimmunized controls. This suggests that the development of pathology following an IN infection of vaccinated animals was independent of bacterial load and may have been driven instead by the adaptive immune response generated following immunization. This identifies a disconnection between the control of infection and the development of pathology, which may influence the design of future vaccines. Citation: O’Meara CP, Armitage CW, Harvie MCG, Timms P, Lycke NY, et al. (2013) Immunization with a MOMP-Based Vaccine Protects Mice against a Pulmonary Chlamydia Challenge and Identifies a Disconnection between Infection and Pathology. PLoS ONE 8(4): e61962. doi:10.1371/journal.pone.0061962 Editor: Paulo Lee Ho, Instituto Butantan, Brazil Received October 3, 2012; Accepted March 16, 2013; Published April 16, 2013 Copyright: ß 2013 O’Meara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the Australian Research Council and Biovitrum (LP0884020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: This work was partly funded by Biovitrum, former owner of the exclusive licensing rights to CTA1-DD. Today the exclusive licensing rights to and ownership of CTA1-DD belongs to the inventors (Dr. Lycke and Dr Lo ¨ wenadler) who have no commercial interests being explored. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. * E-mail: k2.beagley@qut.edu.au Introduction Serological evidence suggests that 80% of people will contract a C. pneumoniae respiratory tract infection at one point in their lifetime [1]. In addition to respiratory tract infections, C. pneumoniae infections are implicated in the exacerbation of cardiovascular disease, asthma, chronic obstructive pulmonary disease, multiple sclerosis, Alzheimer’s disease and reactive arthritis [2,3]. Many of these diseases have multi-billion dollar healthcare expenditures and are leading causes of morbidity and mortality in most nations. Confounding the matter of infection control, most acute C. pneumoniae respiratory infections are difficult to diagnose and treat [4,5]. Furthermore, around 75% of first infections occur between the ages of 5–14 years [6], highlighting the need for early intervention to prevent infection and the potential predisposition/ exacerbation of chronic inflammatory diseases. Consequently, development of a vaccine is most logical solution suited to controlling the spread of infection. Chlamydiae are obligate intracellular pathogens that infect through and predominantly reside in the mucosal epithelium. Protection against infection therefore, is reliant on the induction of a mucosal immune response at the anatomical portal of entry of the invading pathogen [7]. Vaccines targeted to mucosal epithelia, without the necessity for needles, elicit mucosal immunity by stimulating local innate cell populations that are preconditioned to generate adaptive immune responses at mucosal surfaces. How- ever, as immunological tolerance is often the default response to mucosal antigen exposure, any mucosal vaccine must overcome PLOS ONE | www.plosone.org 1 April 2013 | Volume 8 | Issue 4 | e61962