Liposome-based dry powder vaccine immunization targeting the lungs induces broad protection against pneumococcus

Streptococcus pneumoniae is an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported...

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Bibliographic Details
Published in:Journal of controlled release 2024-04, Vol.368, p.184-198
Main Authors: Rodrigues, T.C., Figueiredo, D.B., Gonçalves, V.M., Kaneko, K., Saleem, I.Y., Miyaji, E.N.
Format: Article
Language:English
Subjects:
Animals
Antibodies, Bacterial
Bacterial Proteins
Galactosylceramides
Humans
Immunization
Immunoglobulin G
Liposomes
Lung
Mice
Mice, Inbred BALB C
Mucosal immunity
Pneumococcal Infections - prevention & control
Pneumococcal Vaccines
Pneumonia
Powders
Protein antigen
Streptococcus pneumoniae
Vaccine
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Summary:Streptococcus pneumoniae is an important human pathogen. Currently used conjugate vaccines are effective against invasive disease, but protection is restricted to serotypes included in the formulation, leading to serotype replacement. Furthermore, protection against non-invasive disease is reported to be considerably lower. The development of a serotype-independent vaccine is thus important and Pneumococcal surface protein A (PspA) is a promising vaccine candidate. PspA shows some diversity and can be classified in 6 clades and 3 families, with families 1 and 2 being the most frequent in clinical isolates. The ideal vaccine should thus induce protection against the two most common families of PspA. The aim of this work was to develop a liposome-based vaccine containing PspAs from family 1 and 2 and to characterize its immune response. Liposomes (LP) composed of dipalmitoylphosphatidylcholine (DPPC) and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) with or without α-galactosylceramide (α-GalCer) were produced by microfluidics, encapsulating PspA from clade 1 (PspA1, family 1) and/or clade 4 (PspA4Pro, family 2) followed by spray-drying with trehalose to form nanocomposite microparticles carriers (NCMP). LP/NCMPs showed good stability and preservation of protein activity. LP/NCMPs containing PspA1 and/or PspA4Pro were used for immunization of mice targeting the lungs. High serum IgG antibody titers against both PspA1 and PspA4Pro were detected in animals immunized with LP/NCMPs containing α-GalCer, with a balance of IgG1 and IgG2a titers. IgG in sera from immunized mice bound to pneumococcal strains from different serotypes and expressing different PspA clades, indicating broad recognition. Mucosal IgG and IgA were also detected. Importantly, immunization with LP/NCMPs induced full protection against strains expressing PspAs from family 1 and 2. Furthermore, CD4+ resident memory T cells were detected in the lungs of the immunized animals that survived the challenge. [Display omitted] •Liposomes (LP) composed of DPPC:DC-Chol encapsulated PspA1 and PspA4Pro;•Spray-drying with trehalose formed nanocomposite microparticle carriers (LP/NCMP);•Incorporating α-GalCer to LPs enhanced immune response in lung immunization of mice;•Combining LP/NCMPs with PspA1 and PspA4Pro led to broad recognition of strains;•Combining LP/NCMPs with PspA1 and PspA4Pro induced protection against pneumococci.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2024.02.028