PMID- 1587589
OWN - NLM
STAT- MEDLINE
DA  - 19920623
DCOM- 19920623
LR  - 20091118
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 60
IP  - 6
DP  - 1992 Jun
TI  - Safety, immunogenicity, and efficacy in monkeys and humans of invasive
      Escherichia coli K-12 hybrid vaccine candidates expressing Shigella flexneri 2a
      somatic antigen.
PG  - 2218-24
AB  - A live, oral Shigella vaccine, constructed by transfer of the 140-MDa
      invasiveness plasmid from Shigella flexneri 5 and the chromosomal genes encoding 
      the group- and type-specific O antigen of S. flexneri 2a to Escherichia coli
      K-12, was tested in humans. Designated EcSf2a-1, this vaccine produced adverse
      reactions (fever, diarrhea, or dysentery) in 4 (31%) of 13 subjects who ingested 
      a single dose of 1.0 x 10(9) CFU, while at better-tolerated doses (5.0 x 10(6) to
      5.0 x 10(7) CFU), it provided no significant protection against challenge with S.
      flexneri 2a. A further-attenuated aroD mutant derivative, EcSf2a-2, was then
      tested. Rhesus monkeys that received EcSf2a-2 in three oral doses of ca. 1.5 x
      10(11) CFU experienced no increase in gastrointestinal symptoms compared with a
      control group that received an E. coli K-12 placebo. Compared with controls, the 
      vaccinated monkeys were protected against shigellosis after challenge with S.
      flexneri 2a (60% efficacy; P = 0.001). In humans, EcSf2a-2 was well tolerated at 
      inocula ranging from 5.0 x 10(6) to 2.1 x 10(9) CFU. However, after a single dose
      of 2.5 x 10(9) CFU, 4 (17%) of 23 subjects experienced adverse reactions,
      including fever (3 subjects) and diarrhea (209 ml) (1 subject), and after a
      single dose of 1.8 x 10(10) CFU, 2 of 4 subjects developed dysentery. Recipients 
      of three doses of 1.2 to 2.5 x 10(9) CFU had significant rises in serum antibody 
      to lipopolysaccharide (61%) and invasiveness plasmid antigens (44%) and in
      gut-derived immunoglobulin A antibody-secreting cells specific for
      lipopolysaccharide (100%) and invasiveness plasmid antigens (60%). Despite its
      immunogenicity, the vaccine conferred only 36% protection against illness (fever,
      diarrhea, or dysentery) induced by experimental challenge (P = 0.17). These
      findings illustrate the use of an epithelial cell-invasive E. coli strain as a
      carrier for Shigella antigens. Future studies must explore dosing regimens that
      might optimize the protective effects of the vaccine while eliminating adverse
      clinical reactions.
AD  - Department of Pediatrics, University of Maryland School of Medicine, Baltimore
      21201.
FAU - Kotloff, K L
AU  - Kotloff KL
FAU - Herrington, D A
AU  - Herrington DA
FAU - Hale, T L
AU  - Hale TL
FAU - Newland, J W
AU  - Newland JW
FAU - Van De Verg, L
AU  - Van De Verg L
FAU - Cogan, J P
AU  - Cogan JP
FAU - Snoy, P J
AU  - Snoy PJ
FAU - Sadoff, J C
AU  - Sadoff JC
FAU - Formal, S B
AU  - Formal SB
FAU - Levine, M M
AU  - Levine MM
LA  - eng
PT  - Clinical Trial
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - UNITED STATES
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Vaccines)
RN  - 0 (Vaccines, Synthetic)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Animals
MH  - Antigens, Bacterial/*immunology
MH  - Bacterial Vaccines/*immunology/toxicity
MH  - Escherichia coli/*immunology
MH  - Humans
MH  - Immunization
MH  - Macaca mulatta
MH  - Shigella flexneri/*immunology
MH  - Vaccines, Synthetic/*immunology/toxicity
PMC - PMC257146
OID - NLM: PMC257146
EDAT- 1992/06/01
MHDA- 1992/06/01 00:01
CRDT- 1992/06/01 00:00
PST - ppublish
SO  - Infect Immun. 1992 Jun;60(6):2218-24.