Nasal immunization with recombinant chimeric pneumococcal protein and cell wall from immunobiotic bacteria improve resistance of infant mice to Streptococcus pneumoniae infection.

Jonathan Laiño,Ramiro Ortiz Moyano,Susana Alvarez,Alexander Suvorov,Julio Villena,Hortensia Zelaya,Susana Salva,Paulo Lee Ho

doi:10.1371/journal.pone.0206661

Abstract

Respiratory tract infections and invasive disease caused by Streptococcus pneumoniae in high-risk groups are a major global health problem. Available human vaccines have reduced immunogenicity and low immunological memory in these populations, as well as high cost as a public health strategy in poor communities. In addition, no single pneumococcal protein antigen has been able to elicit protection comparable to that achieved using protein-polysaccharide conjugate vaccines. In this context, chimeric pneumococcal proteins raise as potential good vaccine candidates because of their simplicity of production and reduced cost. The aim of this work was to study whether the nasal immunization of infant mice with the recombinant chimeric pneumococcal protein (PSFP) was able to improve resistance to S. pneumoniae, and whether the immunomodulatory strain Lactobacillus rhamnosus CRL1505 or its cell wall (CW1505) could be used as effective mucosal adjuvants. Our results showed that the nasal immunization with PSPF improved pneumococcal-specific IgA and IgG levels in broncho-alveolar lavage (BAL), reduced lung bacterial counts, and avoided dissemination of pneumococci into the blood. Of interest, immunization with PSPF elicited cross-protective immunity against different pneumococcal serotypes. It was also observed that the nasal immunization of infant mice with PSPF+CW1505 significantly increased the production of pneumococcal-specific IgA and IgG in BAL, as well as IgM and IgG in serum when compared with PSPF alone. PSPF+CW1505 immunization also improved the reduction of pneumococcal lung colonization and its dissemination in to the bloodstream when compared to PSPF alone. Our results suggest that immunization with PSPF together with the cell wall of the immunomodulatory strain L. rhamnosus CRL1505 as a mucosal adjuvant could be an interesting alternative to improve protection against pneumococcal infection in children.

Highlights

Streptococcus pneumoniae is a major global health problem since it is a common cause of respiratory tract infections and invasive disease especially in high-risk groups like children in their first few years of life, elderly and immunocompromised patients
We developed a chimeric protein composed of the fragments of three surface proteins of S. pneumoniae: pneumococcal surface adhesion A (PsaA), pneumococcal surface protein A (PspA) and the surface protein Spr1875 [10]
We demonstrated that the nasal immunization of infant mice with PSPF was able to improve the resistance to the respiratory pathogen S. pneumoniae in lung colonization assays

Summary

Introduction

Streptococcus pneumoniae (the pneumococcus) is a major global health problem since it is a common cause of respiratory tract infections and invasive disease especially in high-risk groups like children in their first few years of life, elderly and immunocompromised patients. The most studied strategy in the development of new effective pneumococcal vaccines involves the use of one or more pneumococcal protein antigens common to all serotypes These vaccines are able to confer non-serotype-dependent protection and represent a more economical approach to reduce pneumococcal infections since they can be produced in highlevels with relatively low cost and they could be more affordable for developing countries. In this regard, virulence factors of protein nature have been studied on the cell surface of S. pneumoniae [4,5] and several of them have been proved immunogenic and able to induce protection against pneumococcal infection in animal models [3]. To date, no single pneumococcal protein antigen has been able to elicit protection comparable to that achieved using protein-polysaccharide conjugate vaccines

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