Immunization with Pneumococcal Surface Protein K of Nonencapsulated Streptococcus pneumoniae Provides Protection in a Mouse Model of Colonization

Abstract

e Current vaccinations are effective against encapsulated strains of Streptococcus pneumoniae, but they do not protect against nonencapsulated Streptococcus pneumoniae (NESp), which is increasing in colonization and incidence of pneumococcal disease. Vaccination with pneumococcal proteins has been assessed for its ability to protect against pneumococcal disease, but several of these proteins are not expressed by NESp. Pneumococcal surface protein K (PspK), an NESp virulence factor, has not been assessed for immunogenic potential or host modulatory effects. Mammalian cytokine expression was determined in an in vivo mouse model and in an in vitro cell culture system. Systemic and mucosal mouse immunization studies were performed to determine the immunogenic potential of PspK. Murine serum and saliva were collected to quantitate specific antibody isotype responses and the ability of antibody and various proteins to inhibit epithelial cell adhesion. Host cytokine response was not reduced by PspK. NESp was able to colonize the mouse nasopharynx as effectively as encapsulated pneumococci. Systemic and mucosal immunization provided protection from colonization by PspK-positive (PspK ؉ ) NESp. Anti-PspK antibodies were recovered from immunized mice and significantly reduced the ability of NESp to adhere to human epithelial cells. A protein-based pneumococcal vaccine is needed to provide broad protection against encapsulated and nonencapsulated pneumococci in an era of increasing antibiotic resistance and vaccine escape mutants. We demonstrate that PspK may serve as an NESp target for nextgeneration pneumococcal vaccines. Immunization with PspK protected against pneumococcal colonization, which is requisite for pneumococcal disease. V accination has been the single most effective means of preventing death by infectious organisms (1). Streptococcus pneumoniae (pneumococcus) is the etiological agent of several human diseases such as pneumonia, sinusitis, otitis media (OM), meningitis, and septicemia (2). The prevalence of invasive pneumococcal disease (IPD) was significantly reduced after the introduction of currently licensed pneumococcal vaccines (3 there is a significant deficit in vaccine coverage of the serological diversity expressed by the species (4). This coverage gap is widened by the increase in nonencapsulated Streptococcus pneumoniae (NESp) carriage since the introduction of the pneumococcal conjugate vaccine (PCV) (5). Pneumococcal disease is predicated by carriage, and NESp is associated with cases of OM and conjunctivitis (6-8). NESp cannot be protected against by current vaccine formulations due to the lack of the capsular polysaccharide. Vaccination with a pneumococcal protein antigen can provide broader pneumococcal protection and be more cost-effective to produce, but a suitable candidate that covers the majority of pneumococci has yet to be developed. While numerous protein-based candidates have been tested, such as PspA, PspC, and PcpA, they have been found to be effective to various degrees based on ...

Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen

“…Because nasopharyngeal colonization of pneumococcus is a prerequisite for pneumococcal infections and because PspK is critical for the nasopharyngeal colonization of NESp, the efficacy of PspK for developing pneumococcal vaccine has been investigated. 18 In this study, the authors found that i.n. immunization with recombinant PspK elicited good protection against nasopharyngeal colonization of not only NESp but the encapsulated strain in mice.…”

“…Moreover, these strains have been shown to exhibit increased antibiotic resistance. [16][17][18][19] The prototype of PspK is a structurally well-characterized cell wall anchoring protein. Its N-terminal and Cterminal ends encode a conserved secretion signal motif and a LPxTG motif for secreting and anchoring on the peptidoglycan layer, respectively.…”

Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis

“…While there have been almost no studies that have examined the mechanisms that allow NESp to persist and cause disease, the chinchilla has emerged as an effective model of OM caused by NESp ( 124 , 131 – 133 ). In this model, the replacement of the cps locus with pspK allowed efficient colonization in the NP along with increased virulence in the middle ear ( 31 , 132 , 134 ). Our study examined the ability of NESp to cause OM in the chinchilla along with the function of PspK during infection.…”

Panel 7 – Pathogenesis of otitis media – a review of the literature between 2015 and 2019

“…Some non-encapsulated pneumococcal lineages express a surface protein, PspK, which is important in bacterial adherence to host epithelia as well as formation of biofilms and persistence in vivo. [16][17][18][19][20] PspK was also shown to increase virulence in encapsulated strains as well [21]. Non-encapsulated pneumococci have also been shown to persist within polymicrobial biofilms and cause OM in conjunction with NTHi [22].…”