Format

Send to

Choose Destination
Vaccine. 2014 Oct 21;32(46):6107-14. doi: 10.1016/j.vaccine.2014.08.083. Epub 2014 Sep 19.

Immunization of cows with novel core glycolipid vaccine induces anti-endotoxin antibodies in bovine colostrum.

Author information

1
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.
2
The Rodale Institute, 611 Siegfriedale Road, Kutztown, PA 19530, United States. Electronic address: penndutch@earthlink.net.
3
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.
4
Bali BioSciences, United States. Electronic address: zr3@columbia.edu.
5
Brown University, Alpert School of Medicine, Providence, RI, United States. Electronic address: Steven_Opal@brown.edu.
6
Fina Biosolutions LLC, Rockville, MD, United States. Electronic address: AndrewLees@earthlink.net.

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".

CONCLUSION:

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.

KEYWORDS:

Anti-core endotoxin antibody; Bovine colostrum; Endotoxemia; Lipopolysaccharide

PMID:
25242628
DOI:
10.1016/j.vaccine.2014.08.083
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center