title: Immunization of cows with novel core glycolipid vaccine induces anti-endotoxin antibodies in bovine colostrum.
abstract: BACKGROUND
  Translocation of gut-derived Gram-negative bacterial (GNB) lipopolysaccharide (LPS, or endotoxin) is a source of systemic inflammation that exacerbates HIV, cardiovascular and gastrointestinal diseases and malnutrition. The oral administration of bovine colostrum (BC) reduces endotoxemia in patients with impaired gut barrier function. Consequently, BC enriched in antibodies to LPS may ameliorate endotoxemia-related morbidities. We developed a detoxified J5 LPS/group B meningococcal outer membrane protein (J5dLPS/OMP) vaccine that induces antibodies against a highly conserved core region of LPS and protects against heterologous GNB infection. We now examine the ability of this vaccine to elicit anti-core endotoxin antibodies in BC.
  
  
  METHODS
  Two cohorts of pregnant cows were immunized with this vaccine in combination with FICA (Cohort 1) or Emulsigen-D (Cohort 2) adjuvants. Antibody responses to the J5 core LPS antigen were measured in both serum and colostrum and compared to antibody levels elicited by a commercially available veterinary vaccine (J5 Bacterin) comprised of heat-killed Escherichia coli O111, J5 mutant bacteria, from which the J5 LPS was purified.
  
  
  RESULTS
  The J5dLPS/OMP vaccine induced high titers of serum IgG antibody to J5 LPS in all seven cows. Both IgG and to a lesser extent IgA anti-J5 LPS antibodies were generated in the colostrum. The J5dLPS/OMP vaccine was significantly more immunogenic in mice than was the J5 Bacterin. BC enriched in anti-J5 LPS antibody reduced circulating endotoxin levels in neutropenic rats, a model of "leaky gut".
  
  
  CONCLUSIONS
  The J5dLPS/OMP vaccine elicits high titers of serum anti-endotoxin antibodies in cows that is passed to the colostrum. This BC enriched in anti-core LPS antibodies has the potential to reduce endotoxemia and ameliorate endotoxin-related systemic inflammation in patients with impaired gut barrier function. Since this vaccine is significantly more immunogenic than the J5 Bacterin vaccine, this J5dLPS/OMP vaccine might prove to be more useful for veterinary indications as well.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 1, Suite 480, Baltimore 21201, United States. Electronic address: across@medicine.umaryland.edu.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Cross
authors.affiliation: The Rodale Institute, 611 Siegfriedale Road, Kutztown, PA 19530, United States. Electronic address: penndutch@earthlink.net.
authors.forename: Hubert J
authors.initials: HJ
authors.lastname: Karreman
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 1, Suite 480, Baltimore 21201, United States. Electronic address: lzhang@medicine.umaryland.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Bali BioSciences, United States. Electronic address: zr3@columbia.edu.
authors.forename: Zeil
authors.initials: Z
authors.lastname: Rosenberg
authors.affiliation: Brown University, Alpert School of Medicine, Providence, RI, United States. Electronic address: Steven_Opal@brown.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Opal
authors.affiliation: Fina Biosolutions LLC, Rockville, MD, United States. Electronic address: AndrewLees@earthlink.net.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D002417:Cattle; D003126:Colostrum / Q000276:immunology*; D019446:Endotoxemia / Q000517:prevention & control*; D005260:Female; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology*; D008813:Mice, Inbred ICR; D038541:Neisseria meningitidis, Serogroup B; D009503:Neutropenia / Q000276:immunology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007136:Immunoglobulins; C042866:antilipopolysaccharide antibodies
keywords: Anti-core endotoxin antibody; Bovine colostrum; Endotoxemia; Lipopolysaccharide