Analysis of anamnestic immune responses in adult horses and priming in neonates induced by a DNA vaccine expressing the vapA gene of Rhodococcus equi.
Abstract: Rhodococcus equi remains one of the most important pathogens of early life in horses, yet conventional vaccines to prevent rhodococcal pneumonia have not been successful. DNA vaccination offers an alternative to conventional vaccines with specific advantages for immunization of neonates. We developed a DNA vaccine expressing the vapA gene (pVR1055vapA) that induced an anamnestic response characterized by virulence associated protein A (VapA)-specific IgG antibodies in sera and bronchoalveolar lavage fluid (BALF) as well as VapA-specific proliferation of pulmonary lymphocytes when tested in adult ponies. In contrast, none of the adults receiving the control plasmid responded. To determine if pVR1055vapA induced VapA-specific responses in the foal, the targeted age group for vaccination against R. equi, 10 naïve foals were randomly assigned at birth to two groups of five. At 8-15 days of age (day 1), foals were vaccinated by intranasal and intradermal (i.d.) routes with either pVR1055vapA or the negative control pVR1055vapA_rev. All foals were DNA boosted at day 14 and protein boosted at day 30 with either recombinant VapA or recombinant CAT (control group). Prior to the protein boost, neither group developed VapA-specific immune responses. However, at day 45, two of the VR1055vapA-vaccinated foals had increased titers of VapA-specific IgGb, IgM and IgGa in the sera, and IgG in the BALF. The induction of the opsonizing isotypes IgGa and IgGb has been previously shown to be associated with protection against R. equi. No VapA-specific immune responses were detected in the control group. This study indicates that the DNA vaccine effectively stimulates anamnestic systemic and pulmonary immune responses in adult horses. The results in foals suggest that the DNA vaccine also primed a subset of immunized neonates. These data support further development and modification to produce a DNA vaccine to more effectively prime neonatal foals.
Publication Date: 2003-08-19 PubMed ID: 12922115DOI: 10.1016/s0264-410x(03)00329-3Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates a developed DNA vaccine expressing the vapA gene, a significant cause of pneumonia in young horses. The vaccine appears to stimulate strong immune responses in adult horses, and preliminary results suggest it may also prime the immune response in neonate horses.
Research Background
- The study tackles Rhodococcus equi, a major pathogen that affects young foals and leads to rhodococcal pneumonia. Current vaccines have not been effective in combating this issue.
- The research team developed a DNA vaccine expressing the vapA gene, a constituent of R. equi. This type of vaccine proposes an alternative to typical vaccines and is beneficial for neonatal immunization.
The DNA Vaccine Efficacy in Adult Horses
- The study tested the DNA vaccine, known as pVR1055vapA, on adult ponies. The ponies exhibited an anamnestic response, a re-stimulation of the immune system characterized by the production of specific IgG antibodies against VapA in their blood serum and bronchoalveolar lavage fluid (BALF).
- Furthermore, there was a significant proliferation of VapA-specific pulmonary lymphocytes, indicating a strong immune response.
- Comparatively, none of the adult ponies receiving the control plasmid exhibited these immune responses.
Priming Immune Response in Neonates
- The research aimed to test the effect of the DNA vaccine on foals, the primary age group impacted by R. equi. They randomly assigned ten naïve foals into two groups of five.
- The foals were then subjected to the DNA vaccine via intranasal and intradermal routes. They were later subjected to a DNA boost and a protein boost.
- Before the protein boost, none of the foals developed VapA-specific immune responses. However, post the protein boost, two of the foals vaccinated with VR1055vapA had heightened levels of VapA-specific IgGb, IgM, and IgGa in their blood serum, and IgG in their BALF.
- The presence of IgGa and IgGb antibodies generally indicates protection against R. equi.
- No specific immune responses were detected in the control group.
Research Implications
- The study findings showcase that the developed DNA vaccine instigates a robust anamnestic immune response in adult horses. The immune response in foals indicates that the DNA vaccine may be effective in priming neonates’ immune systems.
- The positive results gathered from this research lead to the possibility of further development and modification of the DNA vaccine to provide a more efficient defense for neonatal foals against R. equi.
Cite This Article
APA
Lopez AM, Hines MT, Palmer GH, Knowles DP, Alperin DC, Hines SA.
(2003).
Analysis of anamnestic immune responses in adult horses and priming in neonates induced by a DNA vaccine expressing the vapA gene of Rhodococcus equi.
Vaccine, 21(25-26), 3815-3825.
https://doi.org/10.1016/s0264-410x(03)00329-3 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University, P.O. Box 647040, Pullman, WA 99164-7040, USA.
MeSH Terms
- Actinomycetales Infections / immunology
- Actinomycetales Infections / prevention & control
- Actinomycetales Infections / veterinary
- Animals
- Animals, Newborn / immunology
- Antibodies, Bacterial / biosynthesis
- Bacterial Proteins / immunology
- Bacterial Vaccines / immunology
- CD4-Positive T-Lymphocytes / immunology
- COS Cells
- Cell Division / drug effects
- Chlorocebus aethiops
- Cytokines / biosynthesis
- DNA Primers
- Horse Diseases / immunology
- Horse Diseases / prevention & control
- Horses / immunology
- Immunity, Mucosal / immunology
- Immunization Schedule
- Immunization, Secondary
- Immunoblotting
- Immunoglobulin G / biosynthesis
- Immunoglobulin G / immunology
- Immunologic Memory / immunology
- Injections, Intradermal
- Reverse Transcriptase Polymerase Chain Reaction
- Rhodococcus equi / genetics
- Rhodococcus equi / immunology
- Th1 Cells / immunology
- Vaccines, DNA / immunology
- Virulence Factors / immunology
Citations
This article has been cited 9 times.- Kahn SK, Cywes-Bentley C, Blodgett GP, Canaday NM, Turner-Garcia CE, Flores-Ahlschwede P, Metcalfe LL, Nevill M, Vinacur M, Sutter PJ, Meyer SC, Bordin AI, Pier GB, Cohen ND. Randomized, controlled trial comparing Rhodococcus equi and poly-N-acetyl glucosamine hyperimmune plasma to prevent R equi pneumonia in foals.. J Vet Intern Med 2021 Nov;35(6):2912-2919.
- Kahn SK, Cywes-Bentley C, Blodgett GP, Canaday NM, Turner-Garcia CE, Vinacur M, Cortez-Ramirez SC, Sutter PJ, Meyer SC, Bordin AI, Vlock DR, Pier GB, Cohen ND. Antibody activities in hyperimmune plasma against the Rhodococcus equi virulence -associated protein A or poly-N-acetyl glucosamine are associated with protection of foals against rhodococcal pneumonia.. PLoS One 2021;16(8):e0250133.
- Tallmadge RL, Miller SC, Parry SA, Felippe MJB. Antigen-specific immunoglobulin variable region sequencing measures humoral immune response to vaccination in the equine neonate.. PLoS One 2017;12(5):e0177831.
- Giles C, Ndi O, Barton MD, Vanniasinkam T. An Adenoviral Vector Based Vaccine for Rhodococcus equi.. PLoS One 2016;11(3):e0152149.
- Bordin AI, Pillai SD, Brake C, Bagley KB, Bourquin JR, Coleman M, Oliveira FN, Mwangi W, McMurray DN, Love CC, Felippe MJ, Cohen ND. Immunogenicity of an electron beam inactivated Rhodococcus equi vaccine in neonatal foals.. PLoS One 2014;9(8):e105367.
- Ryan C, Giguère S. Equine neonates have attenuated humoral and cell-mediated immune responses to a killed adjuvanted vaccine compared to adult horses.. Clin Vaccine Immunol 2010 Dec;17(12):1896-902.
- Oliveira AF, Ruas LP, Cardoso SA, Soares SG, Roque-Barreira MC. Vaccination of mice with salmonella expressing VapA: mucosal and systemic Th1 responses provide protection against Rhodococcus equi infection.. PLoS One 2010 Jan 13;5(1):e8644.
- Mealey RH, Stone DM, Hines MT, Alperin DC, Littke MH, Leib SR, Leach SE, Hines SA. Experimental Rhodococcus equi and equine infectious anemia virus DNA vaccination in adult and neonatal horses: effect of IL-12, dose, and route.. Vaccine 2007 Oct 23;25(43):7582-97.
- Jacks S, Giguère S, Prescott JF. In vivo expression of and cell-mediated immune responses to the plasmid-encoded virulence-associated proteins of Rhodococcus equi in foals.. Clin Vaccine Immunol 2007 Apr;14(4):369-74.
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