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Vaccine2007; 25(43); 7582-7597; doi: 10.1016/j.vaccine.2007.07.055

Experimental Rhodococcus equi and equine infectious anemia virus DNA vaccination in adult and neonatal horses: effect of IL-12, dose, and route.

Abstract: Improving the ability of DNA-based vaccines to induce potent Type1/Th1 responses against intracellular pathogens in large outbred species is essential. Rhodoccocus equi and equine infectious anemia virus (EIAV) are two naturally occurring equine pathogens that also serve as important large animal models of neonatal immunity and lentiviral immune control. Neonates present a unique challenge for immunization due to their diminished immunologic capabilities and apparent Th2 bias. In an effort to augment R. equi- and EIAV-specific Th1 responses induced by DNA vaccination, we hypothesized that a dual promoter plasmid encoding recombinant equine IL-12 (rEqIL-12) would function as a molecular adjuvant. In adult horses, DNA vaccines induced R. equi- and EIAV-specific antibody and lymphoproliferative responses, and EIAV-specific CTL and tetramer-positive CD8+ T lymphocytes. These responses were not enhanced by the rEqIL-12 plasmid. In neonatal foals, DNA immunization induced EIAV-specific antibody and lymphoproliferative responses, but not CTL. The R. equi vapA vaccine was poorly immunogenic in foals even when co-administered with the IL-12 plasmid. It was concluded that DNA immunization was capable of inducing Th1 responses in horses; dose and route were significant variables, but rEqIL-12 was not an effective molecular adjuvant. Additional work is needed to optimize DNA vaccine-induced Th1 responses in horses, especially in neonates.
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Publication Date: 2007-08-15 PubMed ID: 17889970PubMed Central: PMC3342688DOI: 10.1016/j.vaccine.2007.07.055Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores the effectiveness of DNA-based vaccines against Rhodococcus equi and equine infectious anemia virus (EIAV) in adult and neonatal horses, focusing on the impact of dosage, route of administration, and the potential role of a molecular adjuvant, recombinant equine IL-12.

Background of the Research

  • The study aims to enhance the potency of Type1/Th1 responses against intracellular pathogens in large outbred species, particularly neonates which have reduced immunologic capabilities due to their apparent Th2 bias.
  • R. equi and EIAV are used for this study due to their natural occurrence in horses and their ability to function as significant animal models in studying neonatal immunity and lentiviral immune control.

Research Hypothesis

  • The researchers hypothesized that a dual promoter plasmid encoding recombinant equine IL-12 (rEqIL-12) could act as a molecular adjuvant, improving the Th1 responses induced by DNA vaccination against R. equi and EIAV.

Research Process and Findings

  • In adult horses, DNA vaccines were found to induce specific antibody and lymphoproliferative responses to R. equi and EIAV. This included the activation of EIAV-specific cytotoxic T-lymphocytes (CTL) and tetramer-positive CD8+ T lymphocytes. However, these responses were not enhanced by including rEqIL-12 in the plasmid.
  • For neonatal horses (foals), DNA vaccines elicited specific antibody and lymphoproliferative responses to EIAV but failed to activate CTL. This suggests a reduced efficacy of DNA vaccines in neonates compared to adults.
  • Furthermore, the R. equi vapA vaccine was found to be poorly immunogenic in foals, even when co-administered with the IL-12 plasmid.

Conclusion and Further Work

  • From the study, it was concluded that while DNA vaccines could induce Th1 responses in horses, dosage and route were key variables affecting the success of the immunization.
  • Contrary to the initial hypothesis, the use of rEqIL-12 as a molecular adjuvant did not enhance the vaccine’s efficacy.
  • The researchers suggest more work is needed to improve DNA vaccine-induced Th1 responses in horses, particularly neonates who showed reduced response to vaccination in this study.

Cite This Article

APA
Mealey RH, Stone DM, Hines MT, Alperin DC, Littke MH, Leib SR, Leach SE, Hines SA. (2007). Experimental Rhodococcus equi and equine infectious anemia virus DNA vaccination in adult and neonatal horses: effect of IL-12, dose, and route. Vaccine, 25(43), 7582-7597. https://doi.org/10.1016/j.vaccine.2007.07.055

Publication

Vaccine
ISSN: 0264-410X
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 25
Issue: 43
Pages: 7582-7597

Researcher Affiliations

Mealey, R H
  • Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, Pullman, WA 99164-7040, USA.
Stone, D M
    Hines, M T
      Alperin, D C
        Littke, M H
          Leib, S R
            Leach, S E
              Hines, S A

                MeSH Terms

                • Animals
                • Animals, Newborn
                • Antibodies, Viral / blood
                • CD8-Positive T-Lymphocytes / immunology
                • Drug Administration Routes
                • Enzyme-Linked Immunosorbent Assay
                • Horses
                • Immunization Schedule
                • Infectious Anemia Virus, Equine / immunology
                • Interleukin-12 / genetics
                • Interleukin-12 / immunology
                • Mice
                • NIH 3T3 Cells
                • Recombinant Proteins / immunology
                • Rhodococcus equi / immunology
                • T-Lymphocytes, Cytotoxic / immunology
                • Th1 Cells / immunology
                • Vaccines, DNA / immunology

                Grant Funding

                • K02 AI073101 / NIAID NIH HHS
                • R21 AI058787 / NIAID NIH HHS
                • AI067125 / NIAID NIH HHS
                • AI058787 / NIAID NIH HHS
                • R21 AI067125 / NIAID NIH HHS

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