Development of lactococcal GEM-based pneumococcal vaccines

• Published in: Vaccine 2007-03, Vol.25 (13), p.2497-2506
• Main Authors: Audouy, Sandrine A.L, van Selm, Saskia, van Roosmalen, Maarten L, Post, Eduard, Kanninga, Rolf, Neef, Jolanda, Estevão, Silvia, Nieuwenhuis, Edward E.S, Adrian, Peter V, Leenhouts, Kees, Hermans, Peter W.M
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Allergy and Immunology; Animals; Antibodies, Bacterial - immunology; Antigens; Antigens, Bacterial - immunology; Applied microbiology; Bacteriology; Biological and medical sciences; Cell Movement - immunology; Dendritic Cells - immunology; Disease; Female; Fundamental and applied biological sciences. Psychology; Genes; Gram-positive Enhancer Matrix (GEM); Hybrids; Immunization; Immunoglobulin G - immunology; Lactococcus; Lactococcus lactis - genetics; Lactococcus lactis - immunology; Lactococcus lactis - metabolism; Macrophage Activation - immunology; Macrophages - immunology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Molecular Chaperones - immunology; Mortality; Nasal vaccine; Peptidylprolyl Isomerase - immunology; Plasmids; Pneumococcal Infections - immunology; Pneumococcal Infections - prevention & control; Pneumococcal Vaccines - administration & dosage; Pneumococcal Vaccines - genetics; Pneumococcal Vaccines - immunology; Pneumonia; Proteins; Serine Endopeptidases - immunology; Serine Endopeptidases - metabolism; Streptococcus; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - genetics; Streptococcus pneumoniae - immunology; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2006.09.026

Abstract We report the development of a novel protein-based nasal vaccine against Streptococcus pneumoniae , in which three pneumococcal proteins were displayed on the surface of a non-recombinant, killed Lactococcus lactis -derived delivery system, called Gram-positive Enhancer Matrix (GEM). The GEM particles induced the production of the proinflammatory cytokine tumour necrosis factor-alpha (TNF-α) by macrophages as well as the maturation of dendritic cells. The pneumococcal proteins IgA1 protease (IgA1p), putative proteinase maturation protein A (PpmA) and streptococcal lipoprotein A (SlrA) were anchored in trans to the surface of the GEM particles after recombinant production of the antigens in L. lactis as hybrids with a lactococcal cell wall binding domain, named Protein Anchor domain (PA). Intranasal immunisation with the SlrA-IgA1p or trivalent vaccine combinations without additional adjuvants showed significant protection against fatal pneumococcal pneumonia in mice. The GEM-based trivalent vaccine is a potential pneumococcal vaccine candidate that is expected to be easy to administer, safe and affordable to produce.