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.
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.
Campos
Ivana B
IB
Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil; Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
Darrieux
Michelle
M
Ferreira
Daniela M
DM
Miyaji
Eliane N
EN
Silva
Débora A
DA
Arêas
Ana Paula M
AP
Aires
Karina A
KA
Leite
Luciana C C
LC
Ho
Paulo L
PL
Oliveira
Maria Leonor S
ML
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
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; C051592:pneumococcal surface protein A