PMID- 12210439
OWN - NLM
STAT- MEDLINE
DCOM- 20021203
LR  - 20071114
IS  - 0146-6615 (Print)
IS  - 0146-6615 (Linking)
VI  - 68
IP  - 1
DP  - 2002 Sep
TI  - Systemic and intestinal antibody responses to NSP4 enterotoxin of Wa human 
      rotavirus in a gnotobiotic pig model of human rotavirus disease.
PG  - 119-28
AB  - Antibody responses to the Wa human rotavirus (HRV) nonstructural protein NSP4, a 
      viral enterotoxin, were evaluated in neonatal gnotobiotic (Gn) pigs. Gn pigs were 
      inoculated orally with one dose of 10(5) fluorescent focus units (FFU) of 
      virulent Wa HRV (HRV-V), to mimic natural infection, or with three doses of 5 x 
      10(7) FFU attenuated Wa HRV (HRV-A) at 10-day intervals, to mimic oral attenuated 
      rotavirus vaccines, or they were mock inoculated (mock). Subsets of pigs were 
      challenged with 10(6) FFU of virulent Wa HRV at post-inoculation day 28 (PID 28). 
      Post-challenge, the HRV-V pigs were completely protected against diarrhea and 
      virus shedding, whereas the HRV-A pigs had a 50% protection rate against diarrhea 
      and a 67% protection rate against virus shedding. All mock-inoculated pigs shed 
      virus and had diarrhea post-challenge. Isotype antibody titers to NSP4 were 
      compared in serum and intestinal contents, at post-inoculation day (PID) 28 and 
      at post-challenge day 7 (PCD 7/PID 35) by indirect ELISA, using purified 
      recombinant NH2-6xHis-tagged NSP4 of virulent Wa HRV. Pre-challenge, both the 
      HRV-V and HRV-A-inoculated pigs had similar moderate titers of serum IgG 
      antibodies to NSP4. However, only the HRV-V-inoculated pigs developed detectable 
      serum and intestinal IgA antibody titers to NSP4 pre-challenge, compared with the 
      HRV-A-inoculated pigs. The mock-inoculated pigs had no IgM, IgA, or IgG 
      antibodies to NSP4 pre-challenge. All Wa HRV-inoculated pigs developed low to 
      moderate titers of serum IgM, IgG, and IgA antibodies to NSP4 post-challenge, but 
      the mock-inoculated pigs had only IgM antibodies post-challenge. Both Wa 
      HRV-inoculated groups developed low titers of IgA antibody to NSP4 in the small 
      intestinal contents post-challenge, but titers were 5.8-fold higher in the HRV-V 
      pigs. Our results concur with findings that both rotavirus vaccinated and 
      naturally infected children seroconvert with modest IgG antibodies to NSP4 
      [Johansen et al. (1999) J Med Virol 59:369-367]. These data suggest that Gn pigs 
      could be a useful model to evaluate serum and intestinal IgA antibodies to NSP4 
      and their role in protection against HRV infection. Further experiments may 
      clarify whether (1) the NSP4 antibodies detected pre-challenge in the HRV-V pigs 
      contribute to the higher protection rates observed, or (2) the reduced or delayed 
      NSP4 antibody responses of the HRV-A pigs are associated with the lower 
      protection rates in these pigs.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Iosef, Cristiana
AU  - Iosef C
AD  - Department of Veterinary Preventive Medicine, Food Animal Health Research 
      Program, Ohio Agricultural Research and Development Center, The Ohio State 
      University, Wooster, Ohio, 44691-4096, USA.
FAU - Chang, Kyeong-Ok
AU  - Chang KO
FAU - Azevedo, Marli S P
AU  - Azevedo MS
FAU - Saif, Linda J
AU  - Saif LJ
LA  - eng
GR  - R01AI33561/AI/NIAID NIH HHS/United States
GR  - R01AI37111/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Med Virol
JT  - Journal of medical virology
JID - 7705876
RN  - 0 (Antibodies, Viral)
RN  - 0 (Antigens, Viral)
RN  - 0 (Enterotoxins)
RN  - 0 (Glycoproteins)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulin Isotypes)
RN  - 0 (Immunoglobulin M)
RN  - 0 (NS28 protein, rotavirus)
RN  - 0 (Toxins, Biological)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies, Viral/blood/*immunology
MH  - Antigens, Viral/genetics/*immunology
MH  - Cell Line
MH  - Diarrhea/blood/*immunology/prevention & control
MH  - Disease Models, Animal
MH  - Enterotoxins/genetics/*immunology
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Germ-Free Life
MH  - Glycoproteins/genetics/*immunology
MH  - Humans
MH  - Immunoglobulin A/blood/immunology
MH  - Immunoglobulin G/blood/immunology
MH  - Immunoglobulin Isotypes
MH  - Immunoglobulin M/blood/immunology
MH  - Intestines/*immunology
MH  - Kinetics
MH  - Rotavirus/immunology
MH  - Rotavirus Infections/blood/*immunology/prevention & control
MH  - Swine
MH  - Toxins, Biological
MH  - Viral Nonstructural Proteins/genetics/*immunology
EDAT- 2002/09/05 10:00
MHDA- 2002/12/04 04:00
CRDT- 2002/09/05 10:00
PHST- 2002/09/05 10:00 [pubmed]
PHST- 2002/12/04 04:00 [medline]
PHST- 2002/09/05 10:00 [entrez]
AID - 10.1002/jmv.10178 [doi]
PST - ppublish
SO  - J Med Virol. 2002 Sep;68(1):119-28. doi: 10.1002/jmv.10178.