Evaluation of phoP and rpoS mutants of Salmonella enterica serovar Typhi as attenuated typhoid vaccine candidates: virulence and protective immune responses in intranasally immunized mice.
The attenuation and immunoenhancing effects of rpoS and phoP Salmonella enterica serovar strain Typhi (Salmonella typhi) mutants have not been compared. Here, three S. typhi deletion mutants (phoP, rpoS, and rpoS-phoP double mutant) are constructed and these mutants are characterized with respect to invasiveness, virulence, and protective immune response compared with wild-type Ty2. It was found that phoP and phoP-rpoS deletion mutants are less invasive to HT-29 cells than the wild-type Ty2 and the rpoS single-deleted strain. The LD(50) of immunized mice was higher for phoP than for rpoS mutants, and the highest for the phoP-rpoS double mutant. In addition, all S. typhi mutants showed an increase in the specific serum IgG levels and T-cell-mediated immunity, and showed equal protection abilities against a wild-type Ty2 challenge after two rounds of immunization in BALB/c mice. It is concluded that phoP genes appear to play a more important role than rpoS genes in both cellular invasion and virulence of S. typhi, but not in immunogenicity in mice. Furthermore, the data indicate that the phoP-rpoS double mutant may show promise as a candidate for an attenuated typhoid vaccine.
Lee
Hui-Young
HY
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul, Korea.
Cho
Sun-A
SA
Lee
In-Soo
IS
Park
Jong-Hwan
JH
Seok
Seung-Hyeok
SH
Baek
Min-Won
MW
Kim
Dong-Jae
DJ
Lee
Seok-Ho
SH
Hur
Sook-Jin
SJ
Ban
Sang-Ja
SJ
Lee
Yoo-Kyoung
YK
Han
Yang-Keum
YK
Cho
Young-Keun
YK
Park
Jae-Hak
JH
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D012808:Sigma Factor / Q000235:genetics*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014435:Typhoid Fever / Q000276:immunology / Q000517:prevention & control; D014436:Typhoid-Paratyphoid Vaccines / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014774:Virulence
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D012808:Sigma Factor; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated; C069567:sigma factor KatF protein, Bacteria; C061064:PhoP protein, Bacteria