Recent Approaches in Vaccine Development against <b><i>Streptococcus pneumoniae</i></b>

Abstract

Streptococcuspneumoniae is a major cause of morbidity and mortality among children under 5 years of age worldwide. Vaccines have long been used for protection against pneumococcal infections. Capsular polysaccharides of pneumococci are main antigenic components of these vaccines. However, pneumococcal polysaccharide-based vaccines are not able to elicit appropriate immunological responses in young children and cannot induce the immune memory. Thus, pneumococcal conjugate vaccines were developed through chemical coupling of an immunogenic carrier protein to the capsule. The currently available pneumococcal conjugate vaccines elicited protection against the bacterium efficiently. However, these vaccines are expensive to manufacture and have limited serotype coverage. In this mini-review, therefore, we describe approaches attempted by researchers to circumvent the shortcomings of the conjugate vaccines including specifying appropriate cultivation conditions for the production of S. pneumoniae capsular antigens, development of suitable expression systems for the frequently used carrier protein in the conjugate vaccines (cross-reacting material 197), construction of protein-based vaccines, whole-cell vaccines, DNA vaccines, and using antigen delivery vehicles. Future trends in this field are also discussed.

A Synthetic Virus-Like Particle Streptococcal Vaccine Candidate Using B-Cell Epitopes from the Proline-Rich Region of Pneumococcal Surface Protein A

“…The isolated capsular pneumococcal polysaccharides (CPPs) have been used for many years as vaccines to confer serotype-specific, antibody-mediated protection against invasive pneumococcal disease. However, CPPs alone are typically poorly immunogenic, elicit mostly IgM-type antibodies, induce weak protection in children and fail to elicit long-lasting memory responses in adults [ 4 , 5 ]. Second-generation pneumococcal vaccines composed of isolated capsular polysaccharide conjugated to carrier proteins (PCPs) result in improved T-cell dependent immune responses [ 6 , 7 ].…”

“…One promising approach focuses on the development of recombinant subunit vaccines using highly conserved pneumococcal surface proteins and virulence factors [ 4 , 5 , 16 , 17 ], which can be administered together with an immunostimulatory adjuvant [ 16 , 17 ]. Difficulties can arise, however, when the recombinant proteins are unstable or incorrectly folded and/or direct immune responses towards immunodominant polymorphic epitopes irrelevant for protection, while avoiding immune responses against neutralizing conserved epitopes [ 18 ].…”

Intranasal Immunization with the Commensal Streptococcus mitis Confers Protective Immunity against Pneumococcal Lung Infection

“…Current pneumococcal vaccines, pneumococcal conjugate vaccine (PCV) and pneumococcal polysaccharide vaccine (PPSV), fail to provide optimal protection against S. pneumoniae, mainly because (i) vaccine formulations contain only up to 13 to 23 of the 97 known serotypes; (ii) PPSV has low efficacy against pneumococcal pneumonia, and despite covering more serotypes than PCV, is not immunogenic for children; and (iii) PCV has been associated with nonvaccine serotype replacement (5). Current efforts to develop optimal vaccines are focused on increasing the number of serotypes covered by vaccines, adding conserved pneumococcal proteins, but not much success has so far been achieved (6)(7)(8). Approaches to develop a live vaccine based on attenuated S. pneumoniae strains are also under investigation, as they have the potential to elicit responses that more closely resemble natural acquired immunity to S. pneumoniae (9,10).…”

Protective Regulatory T Cell Immune Response Induced by Intranasal Immunization With the Live-Attenuated Pneumococcal Vaccine SPY1 via the Transforming Growth Factor-β1-Smad2/3 Pathway

“…Intraperitoneal immunization and intranasal immunization both induced elevations in IL-10, IL-4, and IL-17A; however, the levels of IL-17A in splenocyte supernatants and nasal washes as well as secretory IgA in saliva in intranasally immunized mice were significantly higher than those in intraperitoneally immunized mice, suggesting better protection against pneumococcal colonization in an intranasal immunization model ( 10 ). In addition, intranasal immunization provided increased protection against lethal pneumococcal challenge at 3 months post-vaccination, and the survival rates for the intranasal immunization model and intraperitoneal immunization model were 100 and 75%, respectively, and this difference can probably be explained by the more rapid clearance of the subcutaneously injected vaccine ( 29 ).…”