Development of subunit vaccines that provide high-level protection and sterilizing immunity against acute inhalational melioidosis

Mary N. Burtnick, Teresa L. Shaffer, Brittany N. Ross, Laura A. Muruato, Elena Sbrana, David DeShazer, Alfredo Torres, Paul J. Brett

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Burkholderia pseudomallei, the etiologic agent of melioidosis, causes severe disease in humans and animals. Diagnosis and treatment of melioidosis can be challenging, and no licensed vaccines currently exist. Several studies have shown that this pathogen expresses a variety of structurally conserved protective antigens that include cell surface polysaccharides and cell-associated and cell-secreted proteins. Based on those findings, such antigens have become important components of the subunit vaccine candidates that we are currently developing. In the present study, the 6-deoxyheptan capsular polysaccharide (CPS) from B. pseudomallei was purified, chemically activated, and covalently linked to recombinant CRM197 diphtheria toxin mutant (CRM197) to produce CPS-CRM197. Additionally, tandem nickelcobalt affinity chromatography was used to prepare highly purified recombinant B. pseudomallei Hcp1 and TssM proteins. Immunization of C57BL/6 mice with CPSCRM197 produced high-titer IgG and opsonizing antibody responses against the CPS component of the glycoconjugate, while immunization with Hcp1 and TssM produced high-titer IgG and robust gamma interferon-secreting T cell responses against the proteins. Extending upon these studies, we found that when mice were vaccinated with a combination of CPS-CRM197 and Hcp1, 100% of the mice survived a lethal inhalational challenge with B. pseudomallei. Remarkably, 70% of the survivors had no culturable bacteria in their lungs, livers, or spleens, indicating that the vaccine formulation had generated sterilizing immune responses. Collectively, these studies help to better establish surrogates of antigen-induced immunity against B. pseudomallei as well as provide valuable insights toward the development of a safe, affordable, and effective melioidosis vaccine.

Original languageEnglish (US)
Article numbere00724-17
JournalInfection and Immunity
Volume86
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Melioidosis
Burkholderia pseudomallei
Subunit Vaccines
Polysaccharides
Immunity
Vaccines
Immunization
Immunoglobulin G
Diphtheria Toxin
Antigens
Proteins
Glycoconjugates
Surface Antigens
Inbred C57BL Mouse
Affinity Chromatography
Interferon-gamma
Antibody Formation
Spleen
Bacteria
T-Lymphocytes

Keywords

  • Burkholderia pseudomallei
  • Capsule
  • Glycoconjugate
  • Hcp1
  • Immunity
  • Inhalation
  • Melioidosis
  • Mouse
  • Protection
  • Vaccines

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Burtnick, M. N., Shaffer, T. L., Ross, B. N., Muruato, L. A., Sbrana, E., DeShazer, D., ... Brett, P. J. (2018). Development of subunit vaccines that provide high-level protection and sterilizing immunity against acute inhalational melioidosis. Infection and Immunity, 86(1), [e00724-17]. https://doi.org/10.1128/IAI.00724-17

Development of subunit vaccines that provide high-level protection and sterilizing immunity against acute inhalational melioidosis. / Burtnick, Mary N.; Shaffer, Teresa L.; Ross, Brittany N.; Muruato, Laura A.; Sbrana, Elena; DeShazer, David; Torres, Alfredo; Brett, Paul J.

In: Infection and Immunity, Vol. 86, No. 1, e00724-17, 01.01.2018.

Research output: Contribution to journalArticle

Burtnick, Mary N. ; Shaffer, Teresa L. ; Ross, Brittany N. ; Muruato, Laura A. ; Sbrana, Elena ; DeShazer, David ; Torres, Alfredo ; Brett, Paul J. / Development of subunit vaccines that provide high-level protection and sterilizing immunity against acute inhalational melioidosis. In: Infection and Immunity. 2018 ; Vol. 86, No. 1.
@article{fbdbe23f8146471ebf4f36056d342f44,
title = "Development of subunit vaccines that provide high-level protection and sterilizing immunity against acute inhalational melioidosis",
abstract = "Burkholderia pseudomallei, the etiologic agent of melioidosis, causes severe disease in humans and animals. Diagnosis and treatment of melioidosis can be challenging, and no licensed vaccines currently exist. Several studies have shown that this pathogen expresses a variety of structurally conserved protective antigens that include cell surface polysaccharides and cell-associated and cell-secreted proteins. Based on those findings, such antigens have become important components of the subunit vaccine candidates that we are currently developing. In the present study, the 6-deoxyheptan capsular polysaccharide (CPS) from B. pseudomallei was purified, chemically activated, and covalently linked to recombinant CRM197 diphtheria toxin mutant (CRM197) to produce CPS-CRM197. Additionally, tandem nickelcobalt affinity chromatography was used to prepare highly purified recombinant B. pseudomallei Hcp1 and TssM proteins. Immunization of C57BL/6 mice with CPSCRM197 produced high-titer IgG and opsonizing antibody responses against the CPS component of the glycoconjugate, while immunization with Hcp1 and TssM produced high-titer IgG and robust gamma interferon-secreting T cell responses against the proteins. Extending upon these studies, we found that when mice were vaccinated with a combination of CPS-CRM197 and Hcp1, 100{\%} of the mice survived a lethal inhalational challenge with B. pseudomallei. Remarkably, 70{\%} of the survivors had no culturable bacteria in their lungs, livers, or spleens, indicating that the vaccine formulation had generated sterilizing immune responses. Collectively, these studies help to better establish surrogates of antigen-induced immunity against B. pseudomallei as well as provide valuable insights toward the development of a safe, affordable, and effective melioidosis vaccine.",
keywords = "Burkholderia pseudomallei, Capsule, Glycoconjugate, Hcp1, Immunity, Inhalation, Melioidosis, Mouse, Protection, Vaccines",
author = "Burtnick, {Mary N.} and Shaffer, {Teresa L.} and Ross, {Brittany N.} and Muruato, {Laura A.} and Elena Sbrana and David DeShazer and Alfredo Torres and Brett, {Paul J.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1128/IAI.00724-17",
language = "English (US)",
volume = "86",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "1",

}

TY - JOUR

T1 - Development of subunit vaccines that provide high-level protection and sterilizing immunity against acute inhalational melioidosis

AU - Burtnick, Mary N.

AU - Shaffer, Teresa L.

AU - Ross, Brittany N.

AU - Muruato, Laura A.

AU - Sbrana, Elena

AU - DeShazer, David

AU - Torres, Alfredo

AU - Brett, Paul J.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Burkholderia pseudomallei, the etiologic agent of melioidosis, causes severe disease in humans and animals. Diagnosis and treatment of melioidosis can be challenging, and no licensed vaccines currently exist. Several studies have shown that this pathogen expresses a variety of structurally conserved protective antigens that include cell surface polysaccharides and cell-associated and cell-secreted proteins. Based on those findings, such antigens have become important components of the subunit vaccine candidates that we are currently developing. In the present study, the 6-deoxyheptan capsular polysaccharide (CPS) from B. pseudomallei was purified, chemically activated, and covalently linked to recombinant CRM197 diphtheria toxin mutant (CRM197) to produce CPS-CRM197. Additionally, tandem nickelcobalt affinity chromatography was used to prepare highly purified recombinant B. pseudomallei Hcp1 and TssM proteins. Immunization of C57BL/6 mice with CPSCRM197 produced high-titer IgG and opsonizing antibody responses against the CPS component of the glycoconjugate, while immunization with Hcp1 and TssM produced high-titer IgG and robust gamma interferon-secreting T cell responses against the proteins. Extending upon these studies, we found that when mice were vaccinated with a combination of CPS-CRM197 and Hcp1, 100% of the mice survived a lethal inhalational challenge with B. pseudomallei. Remarkably, 70% of the survivors had no culturable bacteria in their lungs, livers, or spleens, indicating that the vaccine formulation had generated sterilizing immune responses. Collectively, these studies help to better establish surrogates of antigen-induced immunity against B. pseudomallei as well as provide valuable insights toward the development of a safe, affordable, and effective melioidosis vaccine.

AB - Burkholderia pseudomallei, the etiologic agent of melioidosis, causes severe disease in humans and animals. Diagnosis and treatment of melioidosis can be challenging, and no licensed vaccines currently exist. Several studies have shown that this pathogen expresses a variety of structurally conserved protective antigens that include cell surface polysaccharides and cell-associated and cell-secreted proteins. Based on those findings, such antigens have become important components of the subunit vaccine candidates that we are currently developing. In the present study, the 6-deoxyheptan capsular polysaccharide (CPS) from B. pseudomallei was purified, chemically activated, and covalently linked to recombinant CRM197 diphtheria toxin mutant (CRM197) to produce CPS-CRM197. Additionally, tandem nickelcobalt affinity chromatography was used to prepare highly purified recombinant B. pseudomallei Hcp1 and TssM proteins. Immunization of C57BL/6 mice with CPSCRM197 produced high-titer IgG and opsonizing antibody responses against the CPS component of the glycoconjugate, while immunization with Hcp1 and TssM produced high-titer IgG and robust gamma interferon-secreting T cell responses against the proteins. Extending upon these studies, we found that when mice were vaccinated with a combination of CPS-CRM197 and Hcp1, 100% of the mice survived a lethal inhalational challenge with B. pseudomallei. Remarkably, 70% of the survivors had no culturable bacteria in their lungs, livers, or spleens, indicating that the vaccine formulation had generated sterilizing immune responses. Collectively, these studies help to better establish surrogates of antigen-induced immunity against B. pseudomallei as well as provide valuable insights toward the development of a safe, affordable, and effective melioidosis vaccine.

KW - Burkholderia pseudomallei

KW - Capsule

KW - Glycoconjugate

KW - Hcp1

KW - Immunity

KW - Inhalation

KW - Melioidosis

KW - Mouse

KW - Protection

KW - Vaccines

UR - http://www.scopus.com/inward/record.url?scp=85039762144&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85039762144&partnerID=8YFLogxK

U2 - 10.1128/IAI.00724-17

DO - 10.1128/IAI.00724-17

M3 - Article

VL - 86

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 1

M1 - e00724-17

ER -