title: Passive immunization with Pneumovax® 23 and pneumolysin in combination with vancomycin for pneumococcal endophthalmitis.
abstract: BACKGROUND
  Capsule and pneumolysin (PLY) are two major virulence factors of Streptococcus pneumoniae. S. pneumoniae is one of the leading causes of bacterial endophthalmitis. The aim of this study is to determine whether passive immunization with the 23-valent pneumococcal polysaccharide vaccine (Pneumovax® 23; PPSV23) or PLY protects against pneumococcal endophthalmitis.
  
  
  METHODS
  New Zealand white rabbits were passively immunized with antiserum to PLY, PPSV23, a mixture of PPSV23/PLY, or PBS (mock). Vitreous was infected with a clinical strain of S. pneumoniae. In a separate group of experiments, vancomycin was injected 4 hours post-infection (PI) for each passively immunized group. Severity of infection, bacterial recovery, myeloperoxidase (MPO) activity and percent loss of retinal function were determined.
  
  
  RESULTS
  Passive immunization with each antiserum significantly lowered clinical severity compared to mock immunization (PPSV23 = 9.19, PPSV23/PLY = 10.45, PLY = 8.71, Mock = 16.83; P = 0.0467). A significantly higher bacterial load was recovered from the vitreous of PLY passively immunized rabbits 24 hours PI (7.87 log10 CFU) compared to controls (7.10 log10 CFU; P = 0.0134). Retinas from immunized rabbits were more intact. Vitreous of PLY (2.88 MPO untis/mL) and PPSV23/PLY (2.17) passively immunized rabbits had less MPO activity compared to controls (5.64; P = 0.0480), and both passive immunizations (PLY = 31.34% loss of retinal function, PPSV23/PLY = 27.44%) helped to significantly preserve retinal function compared to controls (64.58%; P = 0.0323). When vancomycin was administered 4 hours PI, all eyes were sterile at 24 hours PI. A significantly lower clinical severity was observed for rabbits administered the combination immunization (5.29) or PPSV23 (5.29) with vancomycin treatment compared to controls (17.68; P = 0.0469).
  
  
  CONCLUSIONS
  Passive immunization with antisera to these antigens is effective in reducing clinical severity of pneumococcal endophthalmitis in rabbits. Addition of vancomycin to immunization is effective at eliminating the bacteria.
authors.affiliation: Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Sanders
authors.forename: Sidney
authors.initials: S
authors.lastname: Taylor
authors.forename: Nathan
authors.initials: N
authors.lastname: Tullos
authors.forename: Erin W
authors.initials: EW
authors.lastname: Norcross
authors.forename: Quincy C
authors.initials: QC
authors.lastname: Moore
authors.forename: Hilary
authors.initials: H
authors.lastname: Thompson
authors.forename: Lauren B
authors.initials: LB
authors.lastname: King
authors.forename: Mary E
authors.initials: ME
authors.lastname: Marquart
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000008:administration & dosage; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004596:Electroretinography; D009877:Endophthalmitis / Q000503:physiopathology / Q000517:prevention & control*; D007116:Immunization, Passive / Q000379:methods*; D011008:Pneumococcal Infections / Q000503:physiopathology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013301:Streptolysins / Q000008:administration & dosage*; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D014640:Vancomycin