PMID- 19858307
OWN - NLM
STAT- MEDLINE
DCOM- 20100121
LR  - 20240317
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 78
IP  - 1
DP  - 2010 Jan
TI  - Genetic fusions of heat-labile (LT) and heat-stable (ST) toxoids of porcine 
      enterotoxigenic Escherichia coli elicit neutralizing anti-LT and anti-STa 
      antibodies.
PG  - 316-25
LID - 10.1128/IAI.00497-09 [doi]
AB  - Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal 
      disease in humans and farm animals. E. coli fimbriae, or colonization factor 
      antigens (CFAs), and enterotoxins, including heat-labile enterotoxins (LT) and 
      heat-stable enterotoxins (ST), are the key virulence factors in ETEC diarrhea. 
      Unlike fimbriae or LT, STa has not often been included as an antigen in 
      development of vaccines against ETEC diarrhea because of its poor immunogenicity. 
      STa becomes immunogenic only after being coupled with a strongly immunogenic 
      carrier protein. However, native or shorter STa antigens either had to retain 
      toxic activity in order to become antigenic or elicited anti-STa antibodies that 
      were not sufficiently protective. In this study, we genetically mutated the 
      porcine LT (pLT) gene for a pLT(192(R-->G)) toxoid and the porcine STa (pSTa) 
      gene for three full-length pSTa toxoids [STa(11(N-->K)), STa(12(P-->F)), and 
      STa(13(A-->Q))] and used the full-length pLT(192) as an adjuvant to carry the 
      pSTa toxoid for pLT(192):pSTa-toxoid fusion antigens. Rabbits immunized with 
      pLT(192):pSTa(12) or pLT(192):pSTa(13) fusion protein developed high titers of 
      anti-LT and anti-STa antibodies. Furthermore, rabbit antiserum and antifecal 
      antibodies were able to neutralize purified cholera toxin (CT) and STa toxin. In 
      addition, preliminary data suggested that suckling piglets born by a sow 
      immunized with the pLT(192):pSTa(13) fusion antigen were protected when 
      challenged with an STa-positive ETEC strain. This study demonstrated that pSTa 
      toxoids are antigenic when fused with a pLT toxoid and that the elicited anti-LT 
      and anti-STa antibodies were protective. This fusion strategy could provide 
      instructive information to develop effective toxoid vaccines against 
      ETEC-associated diarrhea in animals and humans.
FAU - Zhang, Weiping
AU  - Zhang W
AD  - Center for Infectious Disease Research & Vaccinology/Veterinary Science 
      Department, Box 2157, South Dakota State University, Brookings, SD 57006, USA. 
      weiping.zhang@sdstate.edu
FAU - Zhang, Chengxian
AU  - Zhang C
FAU - Francis, David H
AU  - Francis DH
FAU - Fang, Ying
AU  - Fang Y
FAU - Knudsen, David
AU  - Knudsen D
FAU - Nataro, James P
AU  - Nataro JP
FAU - Robertson, Donald C
AU  - Robertson DC
LA  - eng
GR  - R03 AI068766/AI/NIAID NIH HHS/United States
GR  - R21 AI083897/AI/NIAID NIH HHS/United States
GR  - AI083897/AI/NIAID NIH HHS/United States
GR  - AI068766/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091026
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Bacterial Vaccines)
RN  - 0 (Enterotoxins)
RN  - 0 (Escherichia coli Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (heat stable toxin (E coli))
RN  - D9K3SN2LNY (heat-labile enterotoxin, E coli)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Antibodies, Bacterial/*blood
MH  - Antibodies, Neutralizing/*blood
MH  - Bacterial Toxins/*genetics
MH  - Bacterial Vaccines/immunology
MH  - Cyclic GMP
MH  - Enterotoxigenic Escherichia coli/genetics/*metabolism
MH  - Enterotoxins/*genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Escherichia coli Infections/prevention & control/veterinary
MH  - Escherichia coli Proteins/*genetics
MH  - Gene Expression Regulation, Bacterial
MH  - Genetic Engineering
MH  - Rabbits
MH  - Recombinant Proteins
MH  - Swine
MH  - Swine Diseases/immunology/microbiology
PMC - PMC2798211
EDAT- 2009/10/28 06:00
MHDA- 2010/01/22 06:00
PMCR- 2010/07/01
CRDT- 2009/10/28 06:00
PHST- 2009/10/28 06:00 [entrez]
PHST- 2009/10/28 06:00 [pubmed]
PHST- 2010/01/22 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - IAI.00497-09 [pii]
AID - 0497-09 [pii]
AID - 10.1128/IAI.00497-09 [doi]
PST - ppublish
SO  - Infect Immun. 2010 Jan;78(1):316-25. doi: 10.1128/IAI.00497-09. Epub 2009 Oct 26.