Development of lactococcal GEM-based pneumococcal vaccines.
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-alpha) 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.
Audouy
Sandrine A L
SA
BiOMaDe Technology Foundation, Groningen, The Netherlands.
van Selm
Saskia
S
van Roosmalen
Maarten L
ML
Post
Eduard
E
Kanninga
Rolf
R
Neef
Jolanda
J
Estevão
Silvia
S
Nieuwenhuis
Edward E S
EE
Adrian
Peter V
PV
Leenhouts
Kees
K
Hermans
Peter W M
PW
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D013294:Lactococcus lactis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000276:immunology; D019696:Peptidylprolyl Isomerase / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D018832:Molecular Chaperones; D022242:Pneumococcal Vaccines; C110856:proteasome maturation protein; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase; D019696:Peptidylprolyl Isomerase; C508148:SlrA protein, Streptococcus pneumoniae