IbpA DR2 subunit immunization protects calves against Histophilus somni pneumonia

R. S. Geertsema, B. Zekarias, L. La Franco Scheuch, C. Worby, R. Russo, Laurel J Gershwin, D. S. Herdman, K. Lo, L. B. Corbeil

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Histophilus somni is a prevalent cause of pneumonia and septicemia in cattle. Yet evidence for protection against pneumonia by current vaccines is controversial. We have identified a new H. somni virulence factor, IbpA. Previous studies implicated three likely protective subunits or domains in IbpA (A3, A5, and DR2), which were expressed as recombinant GST fusion proteins and purified for systemic vaccination of calves. After two subcutaneous immunizations, calves were challenged intrabronchially with virulent H. somni strain 2336 and clinical signs were monitored for four days before necropsy. Serum samples were collected throughout. At necropsy, the area of gross pneumonia was estimated, bronchial lavage fluid was collected, lesions were cultured and tissue samples were fixed for histopathology. Results showed that calves immunized with IbpA DR2 had a statistically lower percentage of lung with gross lesions than controls, fewer histologic abnormalities in affected areas and no H. somni isolated from residual pneumonic lesions. Calves immunized with the control GST vaccine, IbpA3 or IbpA5 had larger H. somni positive pneumonic lesions. ELISA results for serum antibodies showed that calves immunized with the IbpA DR2 antigen had high IgG1 and IgG2 and lowest IgE responses to the immunizing antigen. Specific IgG responses were also high in the bronchial lavage fluid. High specific serum IgE responses were previously shown to be associated with more severe pneumonia, but high IgG specific anti-IbpA DR2 responses seem to be critically related to protection. Since the IbpA DR2 Fic motif has been shown to cause bovine alveolar cells to retract, we tested the neutralizing ability of pooled serum from the IbpA DR2 immunized group. This pooled serum reduced cytotoxicity by 75-80%, suggesting that the protection was due to antibody neutralization of IbpA cytotoxicity, at least in part. Therefore, IbpA DR2 appears to be an important protective antigen of H. somni. The study shows, for the first time, that immunization with a purified Fic protein protects against disease in a natural host.

Original languageEnglish (US)
Pages (from-to)4805-4812
Number of pages8
JournalVaccine
Volume29
Issue number29-30
DOIs
StatePublished - Jun 24 2011

Fingerprint

Pasteurellaceae
pneumonia
Immunization
Pneumonia
immunization
lesions (animal)
calves
Serum
Immunoglobulin G
lungs
Bronchoalveolar Lavage Fluid
antigens
neutralization
Lung
Immunoglobulin E
cytotoxicity
necropsy
Vaccines
recombinant fusion proteins
vaccines

Keywords

  • Bovine respiratory disease
  • DR2 vaccine
  • Fic cytotoxin
  • Histophilus somni
  • IbpA

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Geertsema, R. S., Zekarias, B., La Franco Scheuch, L., Worby, C., Russo, R., Gershwin, L. J., ... Corbeil, L. B. (2011). IbpA DR2 subunit immunization protects calves against Histophilus somni pneumonia. Vaccine, 29(29-30), 4805-4812. https://doi.org/10.1016/j.vaccine.2011.04.075

IbpA DR2 subunit immunization protects calves against Histophilus somni pneumonia. / Geertsema, R. S.; Zekarias, B.; La Franco Scheuch, L.; Worby, C.; Russo, R.; Gershwin, Laurel J; Herdman, D. S.; Lo, K.; Corbeil, L. B.

In: Vaccine, Vol. 29, No. 29-30, 24.06.2011, p. 4805-4812.

Research output: Contribution to journalArticle

Geertsema, RS, Zekarias, B, La Franco Scheuch, L, Worby, C, Russo, R, Gershwin, LJ, Herdman, DS, Lo, K & Corbeil, LB 2011, 'IbpA DR2 subunit immunization protects calves against Histophilus somni pneumonia', Vaccine, vol. 29, no. 29-30, pp. 4805-4812. https://doi.org/10.1016/j.vaccine.2011.04.075
Geertsema RS, Zekarias B, La Franco Scheuch L, Worby C, Russo R, Gershwin LJ et al. IbpA DR2 subunit immunization protects calves against Histophilus somni pneumonia. Vaccine. 2011 Jun 24;29(29-30):4805-4812. https://doi.org/10.1016/j.vaccine.2011.04.075
Geertsema, R. S. ; Zekarias, B. ; La Franco Scheuch, L. ; Worby, C. ; Russo, R. ; Gershwin, Laurel J ; Herdman, D. S. ; Lo, K. ; Corbeil, L. B. / IbpA DR2 subunit immunization protects calves against Histophilus somni pneumonia. In: Vaccine. 2011 ; Vol. 29, No. 29-30. pp. 4805-4812.
@article{3c40e6f3cf5344c3b974ded438597f24,
title = "IbpA DR2 subunit immunization protects calves against Histophilus somni pneumonia",
abstract = "Histophilus somni is a prevalent cause of pneumonia and septicemia in cattle. Yet evidence for protection against pneumonia by current vaccines is controversial. We have identified a new H. somni virulence factor, IbpA. Previous studies implicated three likely protective subunits or domains in IbpA (A3, A5, and DR2), which were expressed as recombinant GST fusion proteins and purified for systemic vaccination of calves. After two subcutaneous immunizations, calves were challenged intrabronchially with virulent H. somni strain 2336 and clinical signs were monitored for four days before necropsy. Serum samples were collected throughout. At necropsy, the area of gross pneumonia was estimated, bronchial lavage fluid was collected, lesions were cultured and tissue samples were fixed for histopathology. Results showed that calves immunized with IbpA DR2 had a statistically lower percentage of lung with gross lesions than controls, fewer histologic abnormalities in affected areas and no H. somni isolated from residual pneumonic lesions. Calves immunized with the control GST vaccine, IbpA3 or IbpA5 had larger H. somni positive pneumonic lesions. ELISA results for serum antibodies showed that calves immunized with the IbpA DR2 antigen had high IgG1 and IgG2 and lowest IgE responses to the immunizing antigen. Specific IgG responses were also high in the bronchial lavage fluid. High specific serum IgE responses were previously shown to be associated with more severe pneumonia, but high IgG specific anti-IbpA DR2 responses seem to be critically related to protection. Since the IbpA DR2 Fic motif has been shown to cause bovine alveolar cells to retract, we tested the neutralizing ability of pooled serum from the IbpA DR2 immunized group. This pooled serum reduced cytotoxicity by 75-80{\%}, suggesting that the protection was due to antibody neutralization of IbpA cytotoxicity, at least in part. Therefore, IbpA DR2 appears to be an important protective antigen of H. somni. The study shows, for the first time, that immunization with a purified Fic protein protects against disease in a natural host.",
keywords = "Bovine respiratory disease, DR2 vaccine, Fic cytotoxin, Histophilus somni, IbpA",
author = "Geertsema, {R. S.} and B. Zekarias and {La Franco Scheuch}, L. and C. Worby and R. Russo and Gershwin, {Laurel J} and Herdman, {D. S.} and K. Lo and Corbeil, {L. B.}",
year = "2011",
month = "6",
day = "24",
doi = "10.1016/j.vaccine.2011.04.075",
language = "English (US)",
volume = "29",
pages = "4805--4812",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "29-30",

}

TY - JOUR

T1 - IbpA DR2 subunit immunization protects calves against Histophilus somni pneumonia

AU - Geertsema, R. S.

AU - Zekarias, B.

AU - La Franco Scheuch, L.

AU - Worby, C.

AU - Russo, R.

AU - Gershwin, Laurel J

AU - Herdman, D. S.

AU - Lo, K.

AU - Corbeil, L. B.

PY - 2011/6/24

Y1 - 2011/6/24

N2 - Histophilus somni is a prevalent cause of pneumonia and septicemia in cattle. Yet evidence for protection against pneumonia by current vaccines is controversial. We have identified a new H. somni virulence factor, IbpA. Previous studies implicated three likely protective subunits or domains in IbpA (A3, A5, and DR2), which were expressed as recombinant GST fusion proteins and purified for systemic vaccination of calves. After two subcutaneous immunizations, calves were challenged intrabronchially with virulent H. somni strain 2336 and clinical signs were monitored for four days before necropsy. Serum samples were collected throughout. At necropsy, the area of gross pneumonia was estimated, bronchial lavage fluid was collected, lesions were cultured and tissue samples were fixed for histopathology. Results showed that calves immunized with IbpA DR2 had a statistically lower percentage of lung with gross lesions than controls, fewer histologic abnormalities in affected areas and no H. somni isolated from residual pneumonic lesions. Calves immunized with the control GST vaccine, IbpA3 or IbpA5 had larger H. somni positive pneumonic lesions. ELISA results for serum antibodies showed that calves immunized with the IbpA DR2 antigen had high IgG1 and IgG2 and lowest IgE responses to the immunizing antigen. Specific IgG responses were also high in the bronchial lavage fluid. High specific serum IgE responses were previously shown to be associated with more severe pneumonia, but high IgG specific anti-IbpA DR2 responses seem to be critically related to protection. Since the IbpA DR2 Fic motif has been shown to cause bovine alveolar cells to retract, we tested the neutralizing ability of pooled serum from the IbpA DR2 immunized group. This pooled serum reduced cytotoxicity by 75-80%, suggesting that the protection was due to antibody neutralization of IbpA cytotoxicity, at least in part. Therefore, IbpA DR2 appears to be an important protective antigen of H. somni. The study shows, for the first time, that immunization with a purified Fic protein protects against disease in a natural host.

AB - Histophilus somni is a prevalent cause of pneumonia and septicemia in cattle. Yet evidence for protection against pneumonia by current vaccines is controversial. We have identified a new H. somni virulence factor, IbpA. Previous studies implicated three likely protective subunits or domains in IbpA (A3, A5, and DR2), which were expressed as recombinant GST fusion proteins and purified for systemic vaccination of calves. After two subcutaneous immunizations, calves were challenged intrabronchially with virulent H. somni strain 2336 and clinical signs were monitored for four days before necropsy. Serum samples were collected throughout. At necropsy, the area of gross pneumonia was estimated, bronchial lavage fluid was collected, lesions were cultured and tissue samples were fixed for histopathology. Results showed that calves immunized with IbpA DR2 had a statistically lower percentage of lung with gross lesions than controls, fewer histologic abnormalities in affected areas and no H. somni isolated from residual pneumonic lesions. Calves immunized with the control GST vaccine, IbpA3 or IbpA5 had larger H. somni positive pneumonic lesions. ELISA results for serum antibodies showed that calves immunized with the IbpA DR2 antigen had high IgG1 and IgG2 and lowest IgE responses to the immunizing antigen. Specific IgG responses were also high in the bronchial lavage fluid. High specific serum IgE responses were previously shown to be associated with more severe pneumonia, but high IgG specific anti-IbpA DR2 responses seem to be critically related to protection. Since the IbpA DR2 Fic motif has been shown to cause bovine alveolar cells to retract, we tested the neutralizing ability of pooled serum from the IbpA DR2 immunized group. This pooled serum reduced cytotoxicity by 75-80%, suggesting that the protection was due to antibody neutralization of IbpA cytotoxicity, at least in part. Therefore, IbpA DR2 appears to be an important protective antigen of H. somni. The study shows, for the first time, that immunization with a purified Fic protein protects against disease in a natural host.

KW - Bovine respiratory disease

KW - DR2 vaccine

KW - Fic cytotoxin

KW - Histophilus somni

KW - IbpA

UR - http://www.scopus.com/inward/record.url?scp=79960636167&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960636167&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2011.04.075

DO - 10.1016/j.vaccine.2011.04.075

M3 - Article

C2 - 21557979

AN - SCOPUS:79960636167

VL - 29

SP - 4805

EP - 4812

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 29-30

ER -