Understanding host immune responses to pneumococcal proteins in the upper respiratory tract to develop serotype-independent pneumococcal vaccines.

Introduction: Nasopharyngeal colonization is a precondition for mucosal and invasive pneumococcal disease. Prevention of colonization may reduce pneumococcal transmission and disease incidence. Therefore, several protein-based pneumococcal vaccines are currently under investigation. Areas covered: We aimed to better understand the host immune responses to pneumococcal proteins in the upper respiratory tract (URT) that could facilitate the development of serotype-independent pneumococcal vaccines. English peer-reviewed papers reporting immunological mechanisms involved in host immune response to pneumococcal proteins in the URT were retrieved through a PubMed search using the terms 'pneumococcal proteins,' 'nasopharyngeal colonization' and/or 'cellular/humoral host immune response.' Expert opinion: Although pneumococcal protein antigens induce humoral immune responses, as well as IL-17A-mediated immunity, none of them, when used as single antigen, is sufficient to control and broadly protect against pneumococcal colonization. Novel vaccines should contain multiple conserved protein antigens to activate both arms of the immune system and evoke protection against the whole spectrum of pneumococcal variants by reducing, rather than eradicating, pneumococcal carriage. The highest efficacy would likely be achieved when the vaccine is intranasally applied, inducing mucosal immunity and enhancing the first line of defense by restricting pneumococcal density in the URT, which in turn will lead to reduced transmission and protection against disease.

Novel Protein-Based Pneumococcal Vaccines: Assessing the Use of Distinct Protein Fragments Instead of Full-Length Proteins as Vaccine Antigens.

Non-serotype-specific protein-based pneumococcal vaccines have received extensive research focus due to the limitations of polysaccharide-based vaccines. Pneumococcal proteins (PnPs), universally expressed among serotypes, may induce broader immune responses, stimulating humoral and cellular immunity, while being easier to manufacture and less expensive. Such an approach has raised issues mainly associated with sequence/level of expression variability, chemical instability, as well as possible undesirable reactogenicity and autoimmune properties. A step forward employs the identification of highly-conserved antigenic regions within PnPs with the potential to retain the benefits of protein antigens. Besides, their low-cost and stable construction facilitates the combination of several antigenic regions or peptides that may impair different stages of pneumococcal disease offering even wider serotype coverage and more efficient protection. This review discusses the up-to-date progress on PnPs that are currently under clinical evaluation and the challenges for their licensure. Focus is given on the progress on the identification of antigenic regions/peptides within PnPs and their evaluation as vaccine candidates, accessing their potential to overcome the issues associated with full-length protein antigens. Particular mention is given of the use of newer delivery system technologies including conjugation to Toll-like receptors (TLRs) and reformulation into nanoparticles to enhance the poor immunogenicity of such antigens.