Abstract
Vaccine-enhanced disease (VED) occurs as a result of vaccination followed by infection with virulent Mycoplasma pneumoniae. To date VED has prevented development of an efficacious vaccine against this significant human respiratory pathogen. Herein we report that vaccination of BALB/c mice with M. pneumoniae lipid-associated membrane proteins (LAMPs) induces lung lesions consistent with exacerbated disease following challenge, without reducing bacterial loads. Removal of lipid moieties from LAMPs prior to vaccination eliminates VED and reduces bacterial loads after infection. Collectively, these data indicate that lipid moieties of lipoproteins are the causative factors of M. pneumoniae VED.
Highlights
Mycoplasma pneumoniae (Mp) is a highly contagious and widespread human respiratory pathogen causing over 2 million cases of community-acquired pneumonia (CAP) and ~100,000 adult hospitalizations annually in the United States[1]
An initial pilot study indicated that vaccination of BALB/c mice with lipid-associated membrane proteins (LAMPs) resulted in vaccine-enhanced disease (VED) after challenge with virulent Mp
Mycoplasma lipoprotein lipid moieties are known to be potent immunostimulators, inducing expression of inflammatory cytokines such as TNF-α, IL-6, and IL-1β following the recognition of their lipid moieties by Toll-like receptor complexes[20]. Given that these cytokines are frequently associated with immunopathology, we hypothesized that sensitization by Mp lipoprotein lipid moieties during vaccination induces VED upon challenge with virulent Mp
Summary
Mycoplasma pneumoniae (Mp) is a highly contagious and widespread human respiratory pathogen causing over 2 million cases of community-acquired pneumonia (CAP) and ~100,000 adult hospitalizations annually in the United States[1]. Recent studies by our group (and others) have since recapitulated VED in an animal model by utilizing live-attenuated or crude extract Mp vaccine candidates, respectively[10,11,12,13]. In these murine models, VED is characterized by more severe histopathology post-challenge, when compared to sham vaccinated, Mp challenged mice. VED has been observed in vaccine candidates against other Mycoplasma species, making the identification of the causative factors a crucially important task for vaccine development against these atypical pathogens
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