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Adjuvant Activity of Mycobacterium paratuberculosis in Enhancing the Immunogenicity of Autoantigens During Experimental Autoimmune Encephalomyelitis
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A novel multi-antigen virally vectored vaccine against Mycobacterium avium subspecies paratuberculosis

Tim J Bull1, Sarah C Gilbert, Saranya Sridhar

  • 1Department of Cardiovascular Sciences-Surgery, St George's University of London, London, United Kingdom.

Plos One
|November 29, 2007
PubMed
Abstract

Insights

A novel vaccine targeting Mycobacterium avium subspecies paratuberculosis (MAP) proved highly immunogenic in mice. This MAP vaccine attenuated existing infections and protected against subsequent challenges without adverse effects.

Area of Science:

  • Veterinary Medicine
  • Immunology
  • Microbiology

Background:

  • Mycobacterium avium subspecies paratuberculosis (MAP) causes systemic infection and chronic intestinal inflammation in various species, including primates.
  • Human exposure to MAP occurs through contaminated milk and environmental sources.
  • Current MAP vaccines are limited to veterinary use, consisting of attenuated or killed organisms.

Purpose of the Study:

  • To develop and evaluate a novel vaccine against Mycobacterium avium subspecies paratuberculosis.
  • To assess the immunogenicity and efficacy of a fusion protein vaccine (HAV) delivered via DNA, Adenovirus 5 (Ad5), and Modified Vaccinia Ankara (MVA) vectors.
  • To determine if the vaccine can attenuate pre-existing MAP infections and protect against challenge.

Main Methods:

  • A fusion construct (HAV) of MAP secreted and cell surface proteins was developed.
  • HAV was delivered using DNA, Ad5, and MVA vectors.
  • Vaccination protocols (DNA-prime/MVA-boost, Ad5-prime/MVA-boost) were tested in C57BL/6 mice, including those with pre-existing MAP infection.

Main Results:

  • The HAV vaccine was highly immunogenic, inducing significant IFN-gamma ELISPOT responses and antibody production against vaccine antigens and peptides.
  • Vaccination significantly attenuated pre-existing MAP infections in the spleen and liver.
  • The Ad5-prime/MVA-boost protocol conferred protection against subsequent MAP challenge, with no observed adverse effects.

Conclusions:

  • The novel HAV vaccine is a promising candidate for preventing and treating Mycobacterium avium subspecies paratuberculosis infections.
  • The vaccine demonstrated high immunogenicity, safety, and efficacy in a mouse model.
  • Further studies in naturally infected animals and humans are warranted to explore its clinical potential.

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