title: Vaccination of BALB/c mice with an avirulent Mycoplasma pneumoniae P30 mutant results in disease exacerbation upon challenge with a virulent strain.
abstract: Mycoplasma pneumoniae is a significant human respiratory pathogen that causes high morbidity worldwide. No vaccine to prevent M. pneumoniae infection currently exists, since the mechanisms of pathogenesis are poorly understood. To this end, we constructed a P30 cytadhesin mutant (P-130) with a drastically reduced capacity for binding to erythrocytes and an inability to glide on glass substrates. This mutant was determined to be avirulent and cannot survive in the lungs of BALB/c mice. We also ascertained that the previously identified P30 gliding motility mutant II-3R is avirulent and also cannot be recovered from the lungs of mice after infection. Mutant P130 was then assessed for its efficacy as a live attenuated vaccine candidate in mice after challenge with wild-type M. pneumoniae. After vaccination with the P-130 P30 mutant, mice showed evidence of exacerbated disease upon subsequent challenge with the wild-type strain PI1428, which appears to be driven by a Th17 response and corresponding eosinophilia. Our results are in accordance with other reports of vaccine-induced disease exacerbation in rodents and emphasize the need to better understand the basic mechanisms of M. pneumoniae pathogenesis.
authors.affiliation: Center of Excellence for Vaccine Research, University of Connecticut, Storrs, Connecticut, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Szczepanek
authors.forename: S
authors.initials: S
authors.lastname: Majumder
authors.forename: E S
authors.initials: ES
authors.lastname: Sheppard
authors.forename: X
authors.initials: X
authors.lastname: Liao
authors.forename: D
authors.initials: D
authors.lastname: Rood
authors.forename: E R
authors.initials: ER
authors.lastname: Tulman
authors.forename: S
authors.initials: S
authors.lastname: Wyand
authors.forename: D C
authors.initials: DC
authors.lastname: Krause
authors.forename: L K
authors.initials: LK
authors.lastname: Silbart
authors.forename: S J
authors.initials: SJ
authors.lastname: Geary
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics*; D000818:Animals; D001422:Bacterial Adhesion; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D018450:Disease Progression; D004802:Eosinophilia; D004912:Erythrocytes / Q000382:microbiology; D005260:Female; D055786:Gene Knockout Techniques; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D009177:Mycoplasma pneumoniae / Q000235:genetics / Q000276:immunology*; D011019:Pneumonia, Mycoplasma / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D058504:Th17 Cells / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D001428:Bacterial Vaccines; C096205:P30 adhesin, Mycoplasma; D014613:Vaccines, Attenuated