Streptococcus pneumoniae (pneumococcus) is a gram-positive coccus that is a normal resident of the human nasopharynx. This bacterium is an opportunistic cause of many human diseases such as bacteremia, meningitis, otitis media, peritonitis, pneumonia, and sinusitis [1–4]. Likewise, S. pneumoniae has been reported to be a common cause of bacterial endophthalmitis, often as a result of ocular surgery complications [5–7]. One study of note reported that out of 497 cases of bacterial endophthalmitis at the Wills Eye Institute from 1989–2000, S. pneumoniae was one of the top 3 causes of infection in cases that caused pathology in the first 3 days . Intraocular infection with this bacterium often leads to blindness or loss of the eye [7, 9, 10].
One of the major virulence factors of S. pneumoniae is the polysaccharide capsule [11–16]. There are at least 91 different capsule types of S. pneumoniae, and purified capsules from several types have been used as immunogens in vaccines for protection against invasive pneumococcal diseases. Two pneumococcal vaccines are currently licensed for use in the United States and are based on the polysaccharide capsule, the 13-valent conjugate vaccine (Prevnar 13®; Pfizer (formerly Wyeth Pharmaceuticals), New York, NY, USA) and the 23-valent polysaccharide vaccine (Pneumovax® 23; PPSV23; Merck, Whitehouse Station, NJ, USA) [17–19].
Pneumovax® 23 contains purified polysaccharides of the 23 most commonly found serotypes in pneumococcal infections (1, 2, 3, 4, 5, 6B, 7 F, 8, 9 N, 9 V, 10A, 11A, 12 F, 14, 15B, 17 F, 18C, 19 F, 19A, 20, 22 F, 23 F, and 33 F; listed on the drug literature insert). In studies thus far, immune protection has been tested for non-ocular diseases. A study by Jeurissen et al.  elucidated the immune response to the polysaccharides allows protection from certain diseases. Robbins et al.  observed 90% protection from blood isolates and 85% protection from colonization of normally sterile sites by S. pneumoniae with these serotypes. Regarding ocular studies, this laboratory previously showed that capsule is important for pneumococcal endophthalmitis . The pathogenesis of a parent clinical isolate and isogenic capsule mutant were compared in a rabbit endophthalmitis model. Capsule was determined to be important for infection and retinal damage in this model. These findings led to the question of whether PPSV23 could protect the eye from damage observed during pneumococcal endophthalmitis.
Another virulence factor of S. pneumoniae is pneumolysin (PLY), a cholesterol-dependent cytolysin . PLY binds to cholesterol in the membranes of host cells and forms pores, often resulting in cell lysis [23–25]. Pure toxin injected into the vitreous of rabbits shows the same severity of infection as living pneumococcus injected into the vitreous . PLY mutants of S. pneumoniae cause less severe pathology than their parent strains in rabbit models [26, 27]. A previous study by this laboratory showed that vaccination with PLY significantly lowered pathogenesis caused by pneumococcal endophthalmitis in a rabbit model at 24 and 48 hours PI. Vaccination with PLY also significantly lowered retinal damage at 48 hours post-infection (PI) . However, the bacterial load was high in the vitreous and some (albeit much less) ocular damage still occurred in the immunized animals, which prompted further investigation. Due to the previous findings that both capsule and PLY are important in the pathogenesis of pneumococcal endophthalmitis, the current study was undertaken to determine whether antisera specific for pneumococcal capsule, alone or in combination with PLY-antisera, could provide protection against this disease.