DNA immunization confers systemic, but not mucosal, protection against enteroinvasive bacteria.
Naked plasmid DNA (pRc/Y-hsp60) with a cytomegalovirus promoter and a sequence encoding Yersinia enterocolitica 60-kDa heat shock protein (Y-HSP60) was used for vaccination. After intramuscular injection of pRc/Y-hsp60, Y-hsp60 mRNA could be detected by reverse transcription-PCR in muscle, liver and spleen. A single immunization with pRc/Y-hsp60 induced significant Y-HSP60-specific T cell responses after 1 week. IFN-gamma production by spleen cells upon stimulation with Y-HSP60 was strictly dependent on the presence of CD4+ T cells, indicating the generation of a Th1 response upon DNA immunization. DNA immunization in addition induced strong Y-HSP60-specific IgG2a, weak IgG1, but not IgA antibodies. Immunization of BALB/c and C57BL/6 mice with pRc/Y-hsp60 conferred protection against disseminated Y. enterocolitica infection in spleen, but not at the site of mucosal entry, the Peyer's patches. Furthermore, pRc/Y-hsp60 vaccination did not induce cross-protection against related pathogens. Vaccination of beta2-microglobulin- and H2-I-Abeta-deficient mice was not protective, suggesting that both CD4+ and CD8+ T cells are required for protective immunity induced by DNA vaccination.
Noll
A
A
Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, LMU München, Germany.
Bücheler
N
N
Bohn
E
E
Schirmbeck
R
R
Reimann
J
J
Autenrieth
I B
IB
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D002455:Cell Division; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D015009:Yersinia Infections / Q000382:microbiology / Q000517:prevention & control*; D015008:Yersinia enterocolitica / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D018834:Chaperonin 60; D012333:RNA, Messenger; D019444:Vaccines, DNA; D007371:Interferon-gamma