title: Intranasal immunisation with recombinant Lactococcus lactis displaying either anchored or secreted forms of Proteus mirabilis MrpA fimbrial protein confers specific immune response and induces a significant reduction of kidney bacterial colonisation in mice.
abstract: Proteus mirabilis, a common cause of urinary tract infections in humans, can express different fimbriae. MR/P fimbriae may contribute to bacterial colonisation, and its structural protein MrpA represents a promising candidate antigen for mucosal vaccination. Commercial complex vaccines have limited, short-lived protection and are incapable of eliciting mucosal responses against putative antigens related to virulence. The development of mucosal live vaccines using food-grade lactic acid bacterium Lactococcus lactis as antigen vehicle is an attractive alternative and a safe vaccination strategy against P. mirabilis infection. Here, we report the construction of L. lactis strains modified to produce MrpA via two cellular locations, cell wall-anchored and secreted. Protection assays against P. mirabilis infection and evaluation of the immune response generated after immunisation were conducted in a mouse model. MrpA protein was efficiently expressed by L. lactis strain and caused a significant induction of specific serum IgG and IgA in the animals immunised with L. lactis pSEC:mrpA and L. lactis pCWA:mrpA respectively. A significant reduction of renal bacterial colonisation was observed in both groups of mice (P<0.05) after P. mirabilis challenge. This is the first example of a P. mirabilis fimbrial antigen expressed in a food-grade live strain with promising applications in vaccine design.
authors.affiliation: Laboratorio de Microbiología, Instituto de Investigaciones Biológicas Clemente Estable, Av. Italia 3318, CP11600, Montevideo, Uruguay.
authors.forename: Paola
authors.initials: P
authors.lastname: Scavone
authors.forename: Anderson
authors.initials: A
authors.lastname: Miyoshi
authors.forename: Analía
authors.initials: A
authors.lastname: Rial
authors.forename: Alejandro
authors.initials: A
authors.lastname: Chabalgoity
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.forename: Vasco
authors.initials: V
authors.lastname: Azevedo
authors.forename: Pablo
authors.initials: P
authors.lastname: Zunino
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000652:urine; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000032:analysis; D013294:Lactococcus lactis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D011512:Proteus Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D011513:Proteus mirabilis / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D018709:Statistics, Nonparametric; D014552:Urinary Tract Infections / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D014614:Vaccines, Synthetic; C079120:mrpA protein, Proteus mirabilis; D007371:Interferon-gamma