Evaluation of a phoP/phoQ-deleted, aroA-deleted live oral Salmonella typhi vaccine strain in human volunteers

被引:87
作者
Hohmann, EL
Oletta, CA
Miller, SI
机构
[1] Infectious Disease Unit, Gray 5, Massachusetts General Hospital, Boston, MA 02114, Fruit Street
关键词
Salmonella typhi; microbial pathogenesis; clinical trials;
D O I
10.1016/0264-410X(95)00173-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Improved live oral typhoid fever vaccines may be engineered by deletion of Salmonella-specific virulence genes in Salmonella typhi. Ty445, an aroA-deleted S, typhi Ty2 strain also deleted for the phoP/phoQ Salmonella typhimurium virulence regulatory locus, was tested in human volunteers. Volunteers received escalating single doses of the vaccine, subsequently 14 individuals received two doses of 10(10) c.f.u. without significant side-effects. Control vaccinees received four doses of the live oral typhoid vaccine Ty21a. Of controls, 5/8 seroconverted as measured by increases in serum IgG directed against S. typhi O antigen or whole bacterial antigens in ELISAs. Only 2/14 volunteers receiving the experimental vaccine Ty445 seroconverted Although a Delta aroA Delta phoP/phoQ S, typhi strain is overattenuated for use as a typhoid fever vaccine, our data demonstrate that the deletion of the phoP/phoQ locus in S. typhi significantly attenuates this human pathogen.
引用
收藏
页码:19 / 24
页数:6
相关论文
共 31 条
[21]   SAFETY, INFECTIVITY, IMMUNOGENICITY, AND INVIVO STABILITY OF 2 ATTENUATED AUXOTROPHIC MUTANT STRAINS OF SALMONELLA-TYPHI, 541TY AND 543TY, AS LIVE ORAL VACCINES IN HUMANS [J].
LEVINE, MM ;
HERRINGTON, D ;
MURPHY, JR ;
MORRIS, JG ;
LOSONSKY, G ;
TALL, B ;
LINDBERG, AA ;
SVENSON, S ;
BAQAR, S ;
EDWARDS, MF ;
STOCKER, B .
JOURNAL OF CLINICAL INVESTIGATION, 1987, 79 (03) :888-902
[22]  
LEVINE MM, 1989, REV INFECT DIS, V11, pS552
[23]   CHARACTERIZATION OF DEFENSIN RESISTANCE PHENOTYPES ASSOCIATED WITH MUTATIONS IN THE PHOP-VIRULENCE REGULON OF SALMONELLA-TYPHIMURIUM [J].
MILLER, SI ;
PULKKINEN, WS ;
SELSTED, ME ;
MEKALANOS, JJ .
INFECTION AND IMMUNITY, 1990, 58 (11) :3706-3710
[24]   A 2-COMPONENT REGULATORY SYSTEM (PHOP-PHOQ) CONTROLS SALMONELLA-TYPHIMURIUM VIRULENCE [J].
MILLER, SI ;
KUKRAL, AM ;
MEKALANOS, JJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (13) :5054-5058
[25]   A SALMONELLA-TYPHIMURIUM VIRULENCE PROTEIN IS SIMILAR TO A YERSINIA-ENTEROCOLITICA INVASION PROTEIN AND A BACTERIOPHAGE-LAMBDA OUTER-MEMBRANE PROTEIN [J].
PULKKINEN, WS ;
MILLER, SI .
JOURNAL OF BACTERIOLOGY, 1991, 173 (01) :86-93
[26]  
SMITH BP, 1984, AM J VET RES, V45, P2231
[27]   COMPARISON OF THE SAFETY AND IMMUNOGENICITY OF DELTA-AROC DELTA-AROD AND DELTA-CYA DELTA-CRP SALMONELLA-TYPHI STRAINS IN ADULT VOLUNTEERS [J].
TACKET, CO ;
HONE, DM ;
CURTISS, R ;
KELLY, SM ;
LOSONSKY, G ;
GUERS, L ;
HARRIS, AM ;
EDELMAN, R ;
LEVINE, MM .
INFECTION AND IMMUNITY, 1992, 60 (02) :536-541
[28]   CLINICAL ACCEPTABILITY AND IMMUNOGENICITY OF CVD 908 SALMONELLA-TYPHI VACCINE STRAIN [J].
TACKET, CO ;
HONE, DM ;
LOSONSKY, GA ;
GUERS, L ;
EDELMAN, R ;
LEVINE, MM .
VACCINE, 1992, 10 (07) :443-446
[29]   LACK OF IMMUNE-RESPONSE TO THE VI COMPONENT OF A VI-POSITIVE VARIANT OF THE SALMONELLA-TYPHI LIVE ORAL VACCINE STRAIN TY21A IN HUMAN STUDIES [J].
TACKET, CO ;
LOSONSKY, G ;
TAYLOR, DN ;
BARON, LS ;
KOPECKO, D ;
CRYZ, S ;
LEVINE, MM .
JOURNAL OF INFECTIOUS DISEASES, 1991, 163 (04) :901-904
[30]   PARAMETERS THAT INFLUENCE THE EFFICIENCY OF PROCESSING ANTIGENIC EPITOPES EXPRESSED IN SALMONELLA-TYPHIMURIUM [J].
WICK, MJ ;
HARDING, CV ;
NORMARK, SJ ;
PFEIFER, JD .
INFECTION AND IMMUNITY, 1994, 62 (10) :4542-4548