The Effect of Inactivated Mycobacterium Paratuberculosis Vaccine on the Response to a Heterologous Bacterial Challenge in Pigs

Kristoffer Jarlov Jensen*, Mette Sif Hansen, Peter M. H. Heegaard, Christine Stabell Benn, Gregers Jungersen

*Corresponding author for this work

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Abstract

Background: Vaccines may have non-specific effects, affecting resistance to heterologous pathogens. Veterinary vaccines have seldom been investigated for their non-specific effects. However, recent observational studies suggest that an inactivated paratuberculosis vaccine reduced all-cause mortality in goats and cattle. Aim: We tested if vaccination with a killed mycobacterial vaccine may have heterologous effects in swine (Sus domesticus), specifically on the pathogenic and clinical effects of a heterologous challenge with Actinobacillus pleuropneumoniae in young pigs. Methods: Newborn piglets were randomized to vaccination s.c. with the inactivated paratuberculosis vaccine Gudair (Zoetis Inc.) (n = 17) or no vaccine (n = 16). At 4-5 weeks after vaccination, all piglets were challenged intra-nasally with a high (Gudair: n = 8; control: n = 8) or a low (Gudair: n = 9; control: n = 8) dose of the gram-negative bacterium A. pleuropneumoniae causing acute porcine pleuropneumonia. The effect and severity of pathogen challenge was evaluated by measuring acute phase proteins C-reactive protein, haptoglobin and Porcine alpha 1-acid glycoprotein, and by gross pathology 1 day post challenge. Specific and non-specific in vitro cytokine responses to vaccination were evaluated in whole blood before bacterial challenge. Results: The vaccine was immunogenic in the pigs as evidenced by increased IFN-gamma responses to purified protein derivative of Mycobacterium paratuberculosis. However, Gudair vaccine did not affect IL-6 responses. The gross pathology of the lungs as well as the acute phase protein responses after the high A. pleuropneumoniae dose challenge was slightly increased in the vaccinated animals compared with controls, whereas this was not seen in the animals receiving the low-dose bacterial challenge. Conclusion: The inactivated paratuberculosis vaccine exacerbated the pathological and inflammatory effects of an experimental A. pleuropneumoniae infection in young pigs.
Original languageEnglish
Article number1557
JournalFrontiers in Immunology
Volume10
Number of pages11
ISSN1664-3224
DOIs
Publication statusPublished - 2019

Keywords

  • non-specific effects of vaccines
  • heterologous immunity
  • paratuberculosis vaccine
  • actinobacillus pleuropneumoniae
  • pigs (sus domesticus)
  • mycobacterial vaccine

Cite this

Jensen, Kristoffer Jarlov ; Hansen, Mette Sif ; Heegaard, Peter M. H. ; Benn, Christine Stabell ; Jungersen, Gregers. / The Effect of Inactivated Mycobacterium Paratuberculosis Vaccine on the Response to a Heterologous Bacterial Challenge in Pigs. In: Frontiers in Immunology. 2019 ; Vol. 10.
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title = "The Effect of Inactivated Mycobacterium Paratuberculosis Vaccine on the Response to a Heterologous Bacterial Challenge in Pigs",
abstract = "Background: Vaccines may have non-specific effects, affecting resistance to heterologous pathogens. Veterinary vaccines have seldom been investigated for their non-specific effects. However, recent observational studies suggest that an inactivated paratuberculosis vaccine reduced all-cause mortality in goats and cattle. Aim: We tested if vaccination with a killed mycobacterial vaccine may have heterologous effects in swine (Sus domesticus), specifically on the pathogenic and clinical effects of a heterologous challenge with Actinobacillus pleuropneumoniae in young pigs. Methods: Newborn piglets were randomized to vaccination s.c. with the inactivated paratuberculosis vaccine Gudair (Zoetis Inc.) (n = 17) or no vaccine (n = 16). At 4-5 weeks after vaccination, all piglets were challenged intra-nasally with a high (Gudair: n = 8; control: n = 8) or a low (Gudair: n = 9; control: n = 8) dose of the gram-negative bacterium A. pleuropneumoniae causing acute porcine pleuropneumonia. The effect and severity of pathogen challenge was evaluated by measuring acute phase proteins C-reactive protein, haptoglobin and Porcine alpha 1-acid glycoprotein, and by gross pathology 1 day post challenge. Specific and non-specific in vitro cytokine responses to vaccination were evaluated in whole blood before bacterial challenge. Results: The vaccine was immunogenic in the pigs as evidenced by increased IFN-gamma responses to purified protein derivative of Mycobacterium paratuberculosis. However, Gudair vaccine did not affect IL-6 responses. The gross pathology of the lungs as well as the acute phase protein responses after the high A. pleuropneumoniae dose challenge was slightly increased in the vaccinated animals compared with controls, whereas this was not seen in the animals receiving the low-dose bacterial challenge. Conclusion: The inactivated paratuberculosis vaccine exacerbated the pathological and inflammatory effects of an experimental A. pleuropneumoniae infection in young pigs.",
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author = "Jensen, {Kristoffer Jarlov} and Hansen, {Mette Sif} and Heegaard, {Peter M. H.} and Benn, {Christine Stabell} and Gregers Jungersen",
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language = "English",
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The Effect of Inactivated Mycobacterium Paratuberculosis Vaccine on the Response to a Heterologous Bacterial Challenge in Pigs. / Jensen, Kristoffer Jarlov; Hansen, Mette Sif; Heegaard, Peter M. H.; Benn, Christine Stabell; Jungersen, Gregers.

In: Frontiers in Immunology, Vol. 10, 1557, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - The Effect of Inactivated Mycobacterium Paratuberculosis Vaccine on the Response to a Heterologous Bacterial Challenge in Pigs

AU - Jensen, Kristoffer Jarlov

AU - Hansen, Mette Sif

AU - Heegaard, Peter M. H.

AU - Benn, Christine Stabell

AU - Jungersen, Gregers

PY - 2019

Y1 - 2019

N2 - Background: Vaccines may have non-specific effects, affecting resistance to heterologous pathogens. Veterinary vaccines have seldom been investigated for their non-specific effects. However, recent observational studies suggest that an inactivated paratuberculosis vaccine reduced all-cause mortality in goats and cattle. Aim: We tested if vaccination with a killed mycobacterial vaccine may have heterologous effects in swine (Sus domesticus), specifically on the pathogenic and clinical effects of a heterologous challenge with Actinobacillus pleuropneumoniae in young pigs. Methods: Newborn piglets were randomized to vaccination s.c. with the inactivated paratuberculosis vaccine Gudair (Zoetis Inc.) (n = 17) or no vaccine (n = 16). At 4-5 weeks after vaccination, all piglets were challenged intra-nasally with a high (Gudair: n = 8; control: n = 8) or a low (Gudair: n = 9; control: n = 8) dose of the gram-negative bacterium A. pleuropneumoniae causing acute porcine pleuropneumonia. The effect and severity of pathogen challenge was evaluated by measuring acute phase proteins C-reactive protein, haptoglobin and Porcine alpha 1-acid glycoprotein, and by gross pathology 1 day post challenge. Specific and non-specific in vitro cytokine responses to vaccination were evaluated in whole blood before bacterial challenge. Results: The vaccine was immunogenic in the pigs as evidenced by increased IFN-gamma responses to purified protein derivative of Mycobacterium paratuberculosis. However, Gudair vaccine did not affect IL-6 responses. The gross pathology of the lungs as well as the acute phase protein responses after the high A. pleuropneumoniae dose challenge was slightly increased in the vaccinated animals compared with controls, whereas this was not seen in the animals receiving the low-dose bacterial challenge. Conclusion: The inactivated paratuberculosis vaccine exacerbated the pathological and inflammatory effects of an experimental A. pleuropneumoniae infection in young pigs.

AB - Background: Vaccines may have non-specific effects, affecting resistance to heterologous pathogens. Veterinary vaccines have seldom been investigated for their non-specific effects. However, recent observational studies suggest that an inactivated paratuberculosis vaccine reduced all-cause mortality in goats and cattle. Aim: We tested if vaccination with a killed mycobacterial vaccine may have heterologous effects in swine (Sus domesticus), specifically on the pathogenic and clinical effects of a heterologous challenge with Actinobacillus pleuropneumoniae in young pigs. Methods: Newborn piglets were randomized to vaccination s.c. with the inactivated paratuberculosis vaccine Gudair (Zoetis Inc.) (n = 17) or no vaccine (n = 16). At 4-5 weeks after vaccination, all piglets were challenged intra-nasally with a high (Gudair: n = 8; control: n = 8) or a low (Gudair: n = 9; control: n = 8) dose of the gram-negative bacterium A. pleuropneumoniae causing acute porcine pleuropneumonia. The effect and severity of pathogen challenge was evaluated by measuring acute phase proteins C-reactive protein, haptoglobin and Porcine alpha 1-acid glycoprotein, and by gross pathology 1 day post challenge. Specific and non-specific in vitro cytokine responses to vaccination were evaluated in whole blood before bacterial challenge. Results: The vaccine was immunogenic in the pigs as evidenced by increased IFN-gamma responses to purified protein derivative of Mycobacterium paratuberculosis. However, Gudair vaccine did not affect IL-6 responses. The gross pathology of the lungs as well as the acute phase protein responses after the high A. pleuropneumoniae dose challenge was slightly increased in the vaccinated animals compared with controls, whereas this was not seen in the animals receiving the low-dose bacterial challenge. Conclusion: The inactivated paratuberculosis vaccine exacerbated the pathological and inflammatory effects of an experimental A. pleuropneumoniae infection in young pigs.

KW - non-specific effects of vaccines

KW - heterologous immunity

KW - paratuberculosis vaccine

KW - actinobacillus pleuropneumoniae

KW - pigs (sus domesticus)

KW - mycobacterial vaccine

U2 - 10.3389/fimmu.2019.01557

DO - 10.3389/fimmu.2019.01557

M3 - Journal article

C2 - 31333678

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1557

ER -