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.
Highlights
Serological evidence suggests that 80% of people will contract a C. pneumoniae respiratory tract infection at one point in their lifetime [1]
The no infection control group had a net positive weight gain over the 10 day time period, which was significant when compared to infected control animals (P,0.001) and indicated that cachexia was absent in uninfected animals
Immunization with major outer membrane protein (MOMP) and cholera toxin/CpGoligodeoxynucleotide (CT/CpG), by any route, significantly protected animals from the weight loss associated with a chlamydial respiratory tract challenge (P,0.05–0.01) (Figure 1A)
Summary
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]. Development of a vaccine is most logical solution suited to controlling the spread of infection
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