https://orcid.org/0000-0002-0980-8116
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ABSTRACT
Introduction: Lower respiratory tract infections are the fourth cause of death worldwide and pneumococcus is the leading cause of pneumonia. Nonetheless, existing pneumococcal vaccines are less effective against pneumonia than invasive diseases and serotype replacement is a major concern. Protein antigens could induce serotype-independent protection, and mucosal immunization could offer local and systemic immune responses and induce protection against pneumococcal colonization and lung infection.
Areas covered: Immunity induced in the experimental human pneumococcal carriage model, approaches to address the physiological barriers to mucosal immunization and improve delivery of the vaccine antigens, different strategies already tested for pneumococcal mucosal vaccination, including live recombinant bacteria, nanoparticles, bacterium-like particles, and nanogels as well as, nasal, pulmonary, sublingual and oral routes of vaccination.
Expert opinion: The most promising delivery systems are based on nanoparticles, bacterial-like particles or nanogels, which possess greater immunogenicity than the antigen alone and are considered safer than approaches based on living cells or toxoids. These particles can protect the antigen from degradation, eliminating the refrigeration need during storage and allowing the manufacture of dry powder formulations. They can also increase antigen uptake, control release of antigen and trigger innate immune responses.
Article highlights
The existing pneumococcal vaccines are less effective at preventing pneumococcal pneumonia compared to IPD and serotype replacement has been mitigating the benefits of vaccination.
Protein antigens could solve the serotype replacement problem and PspA is one of the most important antigens capable to induce protective immune response.
Generation of local immune response could offer protection against pneumococcal colonization and lung infection.
In order to be administered into the lungs or intranasally, proteins have to be formulated in an adequate delivery system.
The most promising delivery systems for mucosal administration are based on nanoparticles, bacterial-like particles or nanogels, as these formulations possess greater immunogenicity compared to the antigen alone and are considered safer than approaches based on living cells and adjuvanted with toxoids.
The particles can protect the antigen from degradation, increase antigen uptake, control release of antigen and trigger innate immune responses.
Particles can also stabilize the antigen, allowing the manufacture of dry powder formulations, which requires no refrigeration during storage.
Acknowledgments
The authors thank Sao Paulo Research Foundation and Medical Research Council for the joint grant FAPESP-MRC (FAPESP 2016/50413-8 and MR P022758 1) and BactiVac (grant BVNCP-02) for financial support.
Declaration of interest
R MacLoughlin is an employee of Aerogen Ltd, a manufacturer of nebulizers. I Saleem is Lead Inventor of UK Patent Application Number: 1818517.3 - Nanoparticle Delivery System, filled by LJMU. The authors have no other 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 apart from those disclosed.
Reviewer disclosures
A reviewer on this manuscript has disclosed that they have received speaker fees from Pfizer. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.