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Vaccine2002; 20(11-12); 1653-1659; doi: 10.1016/s0264-410x(01)00488-1

Nasal mucosal immunogenicity for the horse of a SeM peptide of Streptococcus equi genetically coupled to cholera toxin.

Abstract: The intranasal immunogenicity of cholera toxin (CT) genetically coupled to peptide sequence aa236-334 (F3) of the SeM protein of Streptococcus equi was studied in five young adult Welsh ponies. All ponies made rapid CTB- and SeMF3-specific serum antibody responses following the first immunization. Specific nasal IgA responses were detected in two ponies 14 days after the first immunization, in another two 14 days after a second immunization on day 14, and in all ponies 28 days after a third immunization on day 42. SeMF3-specific antibody responses in sera and nasal washes were dominated by IgGb and IgA, respectively, and remained elevated for at least 140 days. Strong serum IgGa and IgG(T) responses were also observed. These antibody responses were qualitatively similar to those induced during recovery from equine strangles. Antibody responses in mucosal secretions were boosted in some ponies by immunizations subsequent to the first immunization, but antibodies in serum were never boosted. In vitro survival of S. equi was significantly reduced by SeMF3-specific antibodies in sera obtained 14 days after the second immunization but survival increased in sera collected following subsequent immunizations, possibly due to absence of synthesis of high affinity antibodies. Finally, the susceptibility of all immunized ponies to commingling challenge by S. equi indicated either that SeMF3 lacks protective epitopes or that the antibodies induced by the chimera were not at effective levels.
Publication Date: 2002-02-23 PubMed ID: 11858875DOI: 10.1016/s0264-410x(01)00488-1Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research investigates the ability of a combined vaccine (cholera toxin genetically linked to a Streptococcus equi protein segment) administered through the nose to initiate an immune response in horses. Although the vaccine provoked some immune responses, the horses were still susceptible to a common streptococcal infection, suggesting the solution may lack essential protective elements or the produced antibodies were insufficient.

Overview of research methods

  • The study was conducted on five young adult Welsh ponies.
  • The ponies were immunized intranasally with a solution of cholera toxin (CT) genetically attached to the protein sequence of the Streptococcus equi bacteria (referred as SeMF3 in the study).
  • The ponies underwent three rounds of immunization: the first round, the second one on day 14, and the third on day 42.
  • Blood (serum) samples and nasal washes were collected periodically to analyze the immune responses, specifically checking for the presence of antibodies.

Main findings

  • All ponies rapidly formed serum antibody responses for CTB and SeMF3 after the first immunization.
  • Specific nasal IgA responses were found in two ponies 14 days after the first vaccination, in two more ponies 14 days after the second vaccination, and in all ponies 28 days after the third vaccination.
  • The SeMF3-specific antibody responses in the serum and nasal washes were maintained for at least 140 days.
  • Interestingly, the immune responses were reminiscent of those observed during recovery from equine strangles, a disease caused by the Streptococcus equi bacteria.

Limited protection provided by the vaccine

  • Notably, secondary and subsequent immunizations didn’t enhance antibodies in serum.
  • In vitro tests, where S. equi bacteria were analyzed in the presence of SeMF3-specific antibodies from the sera, showed initial reduction in bacterial survival. However, survival increased with sera collected after subsequent immunizations.
  • Despite these induced immune responses, all immunized ponies were still susceptible to Streptococcus equi when exposed, suggesting that SeMF3 may lack protective epitopes (the part of an antigen that is recognized by the immune system) or the antibodies induced by the chimera (combined vaccine) were not at effective levels.

Cite This Article

APA
Sheoran AS, Artiushin S, Timoney JF. (2002). Nasal mucosal immunogenicity for the horse of a SeM peptide of Streptococcus equi genetically coupled to cholera toxin. Vaccine, 20(11-12), 1653-1659. https://doi.org/10.1016/s0264-410x(01)00488-1

Publication

ISSN: 0264-410X
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 20
Issue: 11-12
Pages: 1653-1659

Researcher Affiliations

Sheoran, A S
  • Gluck Equine Research Center, University of Kentucky, Lexington, KY 40546-0099, USA.
Artiushin, S
    Timoney, J F

      MeSH Terms

      • Administration, Intranasal
      • Animals
      • Antibodies, Bacterial / biosynthesis
      • Antibodies, Bacterial / blood
      • Antigens, Bacterial
      • Bacterial Outer Membrane Proteins / genetics
      • Bacterial Outer Membrane Proteins / immunology
      • Carrier Proteins / genetics
      • Carrier Proteins / immunology
      • Cholera Toxin / administration & dosage
      • Cholera Toxin / genetics
      • Cholera Toxin / immunology
      • Horse Diseases / immunology
      • Horse Diseases / prevention & control
      • Horses
      • Immunity, Mucosal
      • Nasal Mucosa / immunology
      • Streptococcal Infections / immunology
      • Streptococcal Infections / prevention & control
      • Streptococcal Infections / veterinary
      • Streptococcal Vaccines / administration & dosage
      • Streptococcal Vaccines / genetics
      • Streptococcal Vaccines / immunology
      • Streptococcus equi / genetics
      • Streptococcus equi / immunology
      • Vaccines, Synthetic / administration & dosage
      • Vaccines, Synthetic / genetics
      • Vaccines, Synthetic / immunology

      Citations

      This article has been cited 6 times.
      1. Frosth S, Morris ERA, Wilson H, Frykberg L, Jacobsson K, Parkhill J, Flock JI, Wood T, Guss B, Aanensen DM, Boyle AG, Riihimäki M, Cohen ND, Waller AS. Conservation of vaccine antigen sequences encoded by sequenced strains of Streptococcus equi subsp. equi.. Equine Vet J 2023 Jan;55(1):92-101.
        doi: 10.1111/evj.13552pubmed: 35000217google scholar: lookup
      2. Zhao W, Minderman H, Russell MW. Identification and characterization of intestinal antigen-presenting cells involved in uptake and processing of a nontoxic recombinant chimeric mucosal immunogen based on cholera toxin using imaging flow cytometry.. Clin Vaccine Immunol 2014 Jan;21(1):74-84.
        doi: 10.1128/CVI.00452-13pubmed: 24197893google scholar: lookup
      3. Price GA, Masri HP, Hollander AM, Russell MW, Cornelissen CN. Gonococcal transferrin binding protein chimeras induce bactericidal and growth inhibitory antibodies in mice.. Vaccine 2007 Oct 10;25(41):7247-60.
        doi: 10.1016/j.vaccine.2007.07.038pubmed: 17720283google scholar: lookup
      4. Kelly C, Bugg M, Robinson C, Mitchell Z, Davis-Poynter N, Newton JR, Jolley KA, Maiden MC, Waller AS. Sequence variation of the SeM gene of Streptococcus equi allows discrimination of the source of strangles outbreaks.. J Clin Microbiol 2006 Feb;44(2):480-6.
        doi: 10.1128/JCM.44.2.480-486.2006pubmed: 16455902google scholar: lookup
      5. Li Y, Martinez G, Gottschalk M, Lacouture S, Willson P, Dubreuil JD, Jacques M, Harel J. Identification of a surface protein of Streptococcus suis and evaluation of its immunogenic and protective capacity in pigs.. Infect Immun 2006 Jan;74(1):305-12.
        doi: 10.1128/IAI.74.1.305-312.2006pubmed: 16368985google scholar: lookup
      6. Flock M, Jacobsson K, Frykberg L, Hirst TR, Franklin A, Guss B, Flock JI. Recombinant Streptococcus equi proteins protect mice in challenge experiments and induce immune response in horses.. Infect Immun 2004 Jun;72(6):3228-36.