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.