Immunogenicity and protective efficacy offered by a ribosomal-based vaccine from Shigella flexneri 2a.
Shigellosis is a major form of bacillary dysentery caused by Shigella infection. Shigella ribosome-based vaccines (SRV), considered among the potent vaccine candidates, are composed of O-antigen and ribosome isolated from S. flexneri 2a. To investigate the immunogenicity and protective efficacy of SRV, mice were vaccinated with SRV via the intranasal (i.n.) route. Interestingly, robust levels of Shigella-derived LPS-specific IgG and IgA Abs and antibody-forming cells were elicited in systemic and mucosal compartments following two i.n. administrations of SRV. Groups of mice receiving i.n. SRV developed milder pulmonary pneumonia upon challenge with virulent S. flexneri 2a than did those receiving parenteral SRV. We further found that the MyD88-dependent TLR2 signal partially mediates SRV-induced mucosal immunity, with the exception of TLR4- and TLR5-governed innate immunity. Most importantly, polymeric immunoglobulin receptor knockout (pIgR-/-) mice, which lack secretory IgA Ab, were afforded less protective efficacy than were wild-type mice. It can be concluded then that SRV is immunogenic and provides protective efficacy in mice. It can also be surmised that a mucosal SRV vaccine would be particularly relevant in targeting shigellosis, which provokes inflammation in the human colon.
Shim
Doo-Hee
DH
Mucosal Immunology Section, International Vaccine Institute, Seoul National University Research Park, Kwanak-Gu, Seoul 151-818, Republic of Korea.
Chang
Sun-Young
SY
Park
Sung-Moo
SM
Jang
Hyun
H
Carbis
Rodney
R
Czerkinsky
Cecil
C
Uematsu
Satoshi
S
Akira
Shizuo
S
Kweon
Mi-Na
MN
D000281:Administration, Intranasal; D000818:Animals; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D004405:Dysentery, Bacillary / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007156:Immunologic Memory; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D019081:O Antigens / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D012270:Ribosomes / Q000276:immunology*; D022281:Shigella Vaccines / Q000276:immunology*; D012763:Shigella flexneri / Q000276:immunology*; D014611:Vaccination
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D019081:O Antigens; D022281:Shigella Vaccines