Development of a mucosal complex vaccine against oral Salmonella infection in mice.
We examined the immunogenicity of a Salmonella enterica complex vaccine (CV), consisting of flagellin and polysome purified from serotype Typhimurium LT2. CV plus cholera toxin (CT), in three oral doses given at 7-day intervals, conferred complete protection on C57BL/6 mice against lethal oral infection with a wild-type strain. It elicited mucosal IgA > IgG2a > IgG1 and systemic IgG2a > IgG1 > IgA antibodies to flagellin and polysome, and delayed footpad response (DFR) to both antigens. In Peyer's patches (PPs) and lamina propria (LP), IgA was produced under a Th1-dominant environment; CD4+T cells from produced interleukin (IL)-2, interferon (IFN)-gamma, and IL-10 by stimulation with salmonella extract. On the same protocol, flagellin plus CT induced flagellin-specific mucosal and systemic IgA and IgG1 antibodies, CD4+T cells producing IL-10 and IFN-gamma in PPs and LP, and only minimal levels of flagellin-specific DFR. Polysome plus CT induced polysome-specific mucosal and systemic IgG2a in addition to IgG1 and IgA antibodies, CD4+T cells producing IFN-gamma and IL-2 in PPs and LP, and polysome-specific DFR. These two vaccines, however, conferred at most 50-60% survival rates. Our results suggest that polysomes in CV provide effective adjuvant activity for the induction of both mucosal and systemic Th1-biased responses toward flagellin.
Harada
Hiroko
H
Department of Bacteriology, Nara Medical University, Kashihara, Nara 634-8521, Japan.
Nishikawa
Fumiko
F
Higashi
Nobutaka
N
Kita
Eiji
E
D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D005260:Female; D005408:Flagellin / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007422:Intestines / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009061:Mouth Mucosa / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D012107:Research Design; D012480:Salmonella Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; D022562:Salmonella Vaccines; D005408:Flagellin; D002772:Cholera Toxin