title: Nasal immunization of mice with Lactobacillus casei expressing the Pneumococcal Surface Protein A: induction of antibodies, complement deposition and partial protection against Streptococcus pneumoniae challenge.
abstract: Strategies for the development of new vaccines against Streptococcus pneumoniae infections try to overcome problems such as serotype coverage and high costs, present in currently available vaccines. Formulations based on protein candidates that can induce protection in animal models have been pointed as good alternatives. Among them, the Pneumococcal Surface Protein A (PspA) plays an important role during systemic infection at least in part through the inhibition of complement deposition on the pneumococcal surface, a mechanism of evasion from the immune system. Antigen delivery systems based on live recombinant lactic acid bacteria (LAB) represents a promising strategy for mucosal vaccination, since they are generally regarded as safe bacteria able to elicit both systemic and mucosal immune responses. In this work, the N-terminal region of clade 1 PspA was constitutively expressed in Lactobacillus casei and the recombinant bacteria was tested as a mucosal vaccine in mice. Nasal immunization with L. casei-PspA 1 induced anti-PspA antibodies that were able to bind to pneumococcal strains carrying both clade 1 and clade 2 PspAs and to induce complement deposition on the surface of the bacteria. In addition, an increase in survival of immunized mice after a systemic challenge with a virulent pneumococcal strain was observed.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil; Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ivana B
authors.initials: IB
authors.lastname: Campos
authors.forename: Michelle
authors.initials: M
authors.lastname: Darrieux
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Ferreira
authors.forename: Eliane N
authors.initials: EN
authors.lastname: Miyaji
authors.forename: Débora A
authors.initials: DA
authors.lastname: Silva
authors.forename: Ana Paula M
authors.initials: AP
authors.lastname: Arêas
authors.forename: Karina A
authors.initials: KA
authors.lastname: Aires
authors.forename: Luciana C C
authors.initials: LC
authors.lastname: Leite
authors.forename: Paulo L
authors.initials: PL
authors.lastname: Ho
authors.forename: Maria Leonor S
authors.initials: ML
authors.lastname: Oliveira
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis; D007780:Lacticaseibacillus casei / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D011008:Pneumococcal Infections / Q000276:immunology*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D014169:Transformation, Bacterial
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; C051592:pneumococcal surface protein A