Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection.

Tasson C Rodrigues,Nitesh K Kunda,Maria Leonor S Oliveira,Stefanni L Chavez-Rico,Eliane N Miyaji,Daniela M Ferreira,Viviane M Gonçalves,Douglas B Figueiredo,Imran Y Saleem,Alessandra Soares-Schanoski,Daniela Flavia Hozbor

doi:10.1371/journal.pone.0191692

Abstract

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles—NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2.

Highlights

Despite the availability of vaccines, Streptococcus pneumoniae remains an important cause of community acquired pneumonia and invasive pneumococcal disease (IPD)
Mucosal immunization targeting the lungs was done with the resuspension of NP/nanocomposite microparticles (NCMPs) PspA4Pro
We observed a significant increase of IgG titers in serum of mice immunized with PspA4Pro sc and NP/NCMP PspA4Pro compared with saline after the first (Fig 1A) and second doses (Fig 1B)

Summary

Introduction

Despite the availability of vaccines, Streptococcus pneumoniae remains an important cause of community acquired pneumonia and invasive pneumococcal disease (IPD). It has been estimated that 2.7 million deaths occurred globally in 2015 due to lower respiratory infections, of which 704,000 occurred among children younger than 5 years. Pneumococcal pneumonia accounted for 55.8% of deaths due to lower respiratory infection in children younger than 5 years [3], which clearly shows that new vaccine strategies to control the burden of pneumococcal pneumonia are needed. The use of vaccine formulations that induce local immune responses in the lungs could be an interesting approach. Besides the induction of local immune responses, vaccines targeting the lungs would have other advantages over parenteral injection, such as no risks of needle injuries and removal of cold chain requirements in the case of dry powder formulations [7]

Methods

Results

Conclusion