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Vaccine2015; 33(43); 5764-5771; doi: 10.1016/j.vaccine.2015.09.049

Immune modulation of T regulatory cells and IgE responses in horses vaccinated with West Nile virus vaccine combined with a CpG ODN.

Abstract: Hypersensitivity reactions, such as hives or fatal anaphylactic shock, in response to vaccination constitute a health hazard for horses that develop allergies to vaccine components. In such horses vaccination with viral vaccines stimulates an IgE response to non-target antigens. Viral vaccines share contaminating non-target proteins, such as bovine serum albumin (BSA); these antigens can stimulate IgE production with each exposure. We hypothesized that the addition of a CpG oligodeoxynucleotide (ODN) administered in conjunction with a West Nile virus vaccine would decrease the IgE response; through up-regulation of T regulatory cells and T helper 1 cells thus decreasing the potential to induce a type 1 hypersensitivity response. Thirty adult horses were injected with either CpG ODN or control GpC ODN with a killed WNV vaccine. T regulatory cell numbers and BSA specific IgE concentrations were determined pre and post vaccination. Multicolor flow cytometry was used to evaluate expression of CD4, CD25, and intracellular Foxp3 on PBMCs. Serum concentrations of BSA specific IgE were determined by ELISA. Cell culture supernatants from BSA re-stimulated lymphocytes were evaluated for concentrations of IL-2, IL-4, IL-10, and IFN-γ. The inclusion of the CpG ODN significantly increased the differentiation of T regulatory cells in response to antigen in vitro and in vivo. A significant inverse correlation was found between T regulatory cell numbers and serum BSA specific IgE concentrations. These results suggest that we can provide a safer alternate vaccination strategy, particularly for horses that have demonstrated a pro-allergic phenotype.
Publication Date: 2015-09-28 PubMed ID: 26424604DOI: 10.1016/j.vaccine.2015.09.049Google Scholar: Lookup
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  • Journal Article

Summary

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This research investigates whether adding a synthetic DNA molecule (CpG ODN) to the West Nile Virus vaccine for horses reduces the risk of allergic reactions by modifying the immune response. Giving horses this modified vaccine changed the immune response to suppress unwanted reactions, potentially offering a safer immunization option for horses with allergies.

Study Background

  • The motivation behind this research was the problem of hypersensitivity reactions in horses in response to vaccines. When horses develop allergies to vaccine components, it can lead to severe reactions like hives or even deadly anaphylactic shock.
  • This investigation was specifically sparked by the fact that viral vaccines often contain non-target proteins, such as bovine serum albumin (BSA). These foreign proteins can stimulate an unwanted immune response, called the production of IgE, with each subsequent vaccine dose.
  • The researchers hypothesized that they could minimize this IgE response by adding a CpG oligodeoxynucleotide (ODN), a synthetic DNA molecule, to the West Nile Virus (WNV) vaccine used in horses.

Study Design and Methods

  • Thirty adult horses were involved in the study. They were divided into two groups: one received the WNV vaccine with the addition of the CpG ODN, and the other received the WNV vaccine with a control GpC ODN.
  • Researchers measured several factors before and after vaccination. These included the number of T regulatory cells, the concentration of BSA-specific IgE, the expression of specific proteins on PBMCs, serum concentrations of BSA-specific IgE, and concentrations of different interleukins.

Results and Findings

  • Findings confirmed that adding CpG ODN to the WNV vaccine changes the immune response. Specifically, it increased the differentiation of T regulatory cells, which regulate or suppress other parts of the immune system.
  • More T regulatory cells meant less BSA-specific IgE — the antibodies that contribute to allergic reactions.
  • The inverse correlation between T regulatory cell numbers and serum BSA specific IgE concentrations suggests that CpG ODN stimulates regulatory cells that then suppress the animals’ allergic response to the vaccine.

Implications

  • This research could provide a safer alternative vaccination strategy for horses, especially those that have already shown a propensity for allergic reactions.
  • The findings could be applied in the development of vaccines to prevent hypersensitivity reactions in other animals, and potentially even humans.

Cite This Article

APA
Behrens NE, Gershwin LJ. (2015). Immune modulation of T regulatory cells and IgE responses in horses vaccinated with West Nile virus vaccine combined with a CpG ODN. Vaccine, 33(43), 5764-5771. https://doi.org/10.1016/j.vaccine.2015.09.049

Publication

ISSN: 1873-2518
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 33
Issue: 43
Pages: 5764-5771

Researcher Affiliations

Behrens, Nicole E
  • Department of Pathology, Microbiology, and Immunology, VetMed 3A, School of Veterinary Medicine, One Shields Ave., University of California, Davis, CA 95616, United States. Electronic address: nebehrens@ucdavis.edu.
Gershwin, Laurel J
  • Department of Pathology, Microbiology, and Immunology, VetMed 3A, School of Veterinary Medicine, One Shields Ave., University of California, Davis, CA 95616, United States.

MeSH Terms

  • Adjuvants, Immunologic / administration & dosage
  • Allergens / administration & dosage
  • Allergens / immunology
  • Animals
  • Drug Contamination
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Horses
  • Immunoglobulin E / blood
  • Immunophenotyping
  • Male
  • Oligodeoxyribonucleotides / administration & dosage
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • West Nile Virus Vaccines / administration & dosage
  • West Nile Virus Vaccines / immunology