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

ABSTRACT

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.

KEYWORDS:

• Cellular immunity
• colonization
• anti-peptide antibodies
• s. pneumoniae (Streptococcus pneumoniae)
• protection
• protein-based pneumococcal vaccines
• epitope-based pneumococcal vaccines

Article Highlights

• Nasopharyngeal colonization is a precondition for both mucosal and invasive pneumococcal disease.

• Control of nasopharyngeal colonization has the potential to reduce the incidence of pneumococcal transmission and thus pneumococcal disease.

• Novel protein-based pneumococcal vaccines are under investigation to overcome the limitations of currently available polysaccharide-based pneumococcal vaccines.

• A better understanding of mucosal immune responses to pneumococcal proteins is essential for the development of efficacious protein-based pneumococcal vaccines.

• To evoke a broadly protective response, it is essential to combine multiple conserved protein antigens that induce humoral and IL-17A-mediated immunity.

• Irrespective of the route of vaccination, it should be carefully considered to reduce, rather than eliminate, the S. pneumoniae from the upper respiratory tract.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.