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<p>Vaccination against <i>Mycoplasma hyopneumoniae</i> is still carried out worldwide, but unfortunately current commercial vaccines only provide partial protection. Therefore, two <i>M. hyopneumoniae</i> strains were genetically modified by transposon-mediated gene disruption of <i>mmsA</i> and <i>mnuA</i>, encoding methylmalonate semialdehyde dehydrogenase and membrane nuclease A, respectively. We investigated how immune responses elicited by these genetically modified <i>M. hyopneumoniae</i> strains protected pigs against challenge infection. An endotracheal single dose vaccination with genetically modified <i>M. hyopneumoniae</i> strain 1 (Δ<i>mmsA</i>) or 2 (Δ<i>mnuA</i>), or physiological saline solution (Control) was followed by challenge infection. Piglets from Δ<i>mnuA</i> had a higher respiratory disease score post-vaccination, but this group coughed significantly less after challenge. Significantly fewer DNA copies of the challenge strains were observed in broncho-alveolar lavage fluid (BAL) from Δ<i>mnuA</i> after challenge. Two weeks post-challenge, significantly more BAL IgG and BAL IgA was observed in Δ<i>mnuA</i>, but at euthanasia significantly more IgA and less pro-inflammatory cytokines were detected in BAL from both vaccinated groups. Furthermore, a significantly lower percentage of IFN-γ<sup>+</sup> and TNF-α<sup>+</sup>IFN-γ<sup>+</sup> CD8<sup>+</sup> T cells was observed after administration of Δ<i>mnuA.</i> The percentage of IFN-γ<sup>+</sup> CD8<sup>+</sup> T cells was significantly lower in Δ<i>mmsA</i> at euthanasia. To conclude, the results of this exploratory study show that a single endotracheal administration of Δ<i>mnuA</i> resulted in coughing post-vaccination, but reduced clinical signs post-challenge and challenge strain DNA load in BAL. Therefore, a strain mutated in the <i>mnuA</i> gene might be an interesting mutant strain that could be promising as a potential live vaccine candidate strain as it can reduce <i>M. hyopneumoniae</i> infection burden under field conditions.</p>

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Efficacy of genetically modified Mycoplasma hyopneumoniae strains and their effect on local and cell-mediated immune responses in pigs

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月17日

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  • Lisa Beuckelaere,
  • Filip Boyen,
  • Gaël Auray,
  • Maarten Haspeslagh,
  • Eva De Coensel,
  • Bettina Salome Trueeb,
  • Evelyne Meyer,
  • Freddy Haesebrouck,
  • Ward De Spiegelaere,
  • Bert Devriendt,
  • Artur Summerfield,
  • Peter Kuhnert,
  • Dominiek Maes

摘要

Vaccination against Mycoplasma hyopneumoniae is still carried out worldwide, but unfortunately current commercial vaccines only provide partial protection. Therefore, two M. hyopneumoniae strains were genetically modified by transposon-mediated gene disruption of mmsA and mnuA, encoding methylmalonate semialdehyde dehydrogenase and membrane nuclease A, respectively. We investigated how immune responses elicited by these genetically modified M. hyopneumoniae strains protected pigs against challenge infection. An endotracheal single dose vaccination with genetically modified M. hyopneumoniae strain 1 (ΔmmsA) or 2 (ΔmnuA), or physiological saline solution (Control) was followed by challenge infection. Piglets from ΔmnuA had a higher respiratory disease score post-vaccination, but this group coughed significantly less after challenge. Significantly fewer DNA copies of the challenge strains were observed in broncho-alveolar lavage fluid (BAL) from ΔmnuA after challenge. Two weeks post-challenge, significantly more BAL IgG and BAL IgA was observed in ΔmnuA, but at euthanasia significantly more IgA and less pro-inflammatory cytokines were detected in BAL from both vaccinated groups. Furthermore, a significantly lower percentage of IFN-γ+ and TNF-α+IFN-γ+ CD8+ T cells was observed after administration of ΔmnuA. The percentage of IFN-γ+ CD8+ T cells was significantly lower in ΔmmsA at euthanasia. To conclude, the results of this exploratory study show that a single endotracheal administration of ΔmnuA resulted in coughing post-vaccination, but reduced clinical signs post-challenge and challenge strain DNA load in BAL. Therefore, a strain mutated in the mnuA gene might be an interesting mutant strain that could be promising as a potential live vaccine candidate strain as it can reduce M. hyopneumoniae infection burden under field conditions.