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Updated: May 12, 2026
A Non-invasive and Technically Non-intensive Method for Induction and Phenotyping of Experimental Bacterial Pneumonia in Mice
Published on: September 28, 2016
Immunization with a MOMP-based vaccine protects mice against a pulmonary Chlamydia challenge and identifies a
Connor P O'Meara1, Charles W Armitage, Marina C G Harvie
1Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
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 IFNγ, TNFα 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.
Insights
Developing a Chlamydia pneumoniae vaccine is crucial. Sublingual and transcutaneous immunization with major outer membrane protein (MOMP) and CT/CpG adjuvant offered significant protection against infection and lung scarring in mice.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- * Chlamydia pneumoniae causes up to 20% of community-acquired pneumonia.
- * Mild or asymptomatic infections highlight the need for effective vaccines to reduce disease prevalence.
- * Chronic inflammatory diseases can be exacerbated by C. pneumoniae infections.
Purpose of the Study:
- * To evaluate the efficacy of different immunization routes (intranasal, sublingual, transcutaneous) for a C. pneumoniae vaccine.
- * To assess protection against infection and lung pathology using recombinant major outer membrane protein (MOMP) with specific adjuvants.
- * To investigate the immune responses associated with protection and pathology in a mouse model.
Main Methods:
- * C. muridarum mouse model of infection.
- * Immunization via intranasal (IN), sublingual (SL), or transcutaneous (TC) routes with MOMP and adjuvants (CTA1-DD or CT/CpG).
- * Intranasal challenge with C. muridarum and assessment of chlamydial burden, weight loss, and lung pathology (fibrotic scarring).
- * Analysis of antigen-specific immune responses (IFNγ, TNFα, IL-17) in splenocytes and lymph nodes.
Main Results:
- * SL and TC immunization with MOMP and CT/CpG provided significant protection, reducing lung chlamydial burden and preventing weight loss, comparable to live infection.
- * These routes also offered near-complete protection against lung fibrotic scarring, a benefit not seen with prior infection.
- * IN immunization with MOMP protected against infection but not pathology, while TC immunization with MOMP and CTA1-DD protected against pathology despite similar bacterial loads to controls.
Conclusions:
- * Sublingual and transcutaneous immunization routes with MOMP and CT/CpG adjuvant are highly effective in a C. muridarum mouse model.
- * Protection against infection and pathology can be dissociated, suggesting pathology may be driven by the adaptive immune response independent of bacterial load.
- * Findings provide insights for designing future Chlamydia vaccines that target both infection and immunopathology.
