Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid

Stefan Worgall, Anja Krause, Michael Rivara, Kyung Kim Hee, Enrico V. Vintayen, Neil R. Hackett, Peter W. Roelvink, Joseph T. Bruder, Thomas J. Wickham, Imre Kovesdi, Ronald Crystal

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Pseudomonas aeruginosa is an important opportunistic pathogen that can cause chronic and often life-threatening infections of the respiratory tract, particularly in individuals with cystic fibrosis (CF). Because infections with P. aeruginosa remain the major cause of the high morbidity and mortality of CF, a vaccine against P. aeruginosa would be very useful for preventing this disorder. The outer membrane protein F (OprF) of P. aeruginosa is a promising vaccine candidate and various B cell epitopes within OprF have been identified. Given that adenovirus (Ad) vectors have strong immunogenic potential and can function as adjuvants for genetic vaccines, the present study evaluates the immunogenic and protective properties of a novel replication-deficient Ad vector in which the Ad hexon protein was modified to include a 14-amino acid epitope of P. aeruginosa OprF (Epi8) in loop 1 of the hypervariable region 5 of the hexon (AdZ.Epi8). Immunization of C57BL/6 mice with AdZ.Epi8 resulted in detectable serum anti-P. aeruginosa and anti-OprF humoral responses. These responses were haplotype dependent, with higher serum anti-OprF titers in CBA mice than in BALB/c or C57BL/6 mice. AdZ.Epi8 induced Epi8-specific IFN-γ-positive CD4 and CD8 T cell responses and resulted in protection against a lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeated administration of AdZ.Epi8 resulted in boosting of the anti-OprF humoral and anti-Epi8 cellular response, whereas no boosting effect was present in the response against the transgene β-galactosidase. These observations suggest that Ad vectors expressing pathogen epitopes in their capsid will protect against an extracellular pathogen and will allow boosting of the epitope-specific humoral response with repeated administration, a strategy that should prove useful in developing Ad vectors as vaccines where humoral immunity will be protective.

Original languageEnglish
Pages (from-to)1281-1289
Number of pages9
JournalJournal of Clinical Investigation
Volume115
Issue number5
DOIs
Publication statusPublished - 1 May 2005
Externally publishedYes

Fingerprint

Capsid
Adenoviridae
Pseudomonas aeruginosa
Epitopes
Vaccines
Inbred C57BL Mouse
Cystic Fibrosis
Galactosidases
B-Lymphocyte Epitopes
Inbred CBA Mouse
Humoral Immunity
OmpF protein
Serum
Transgenes
Respiratory Tract Infections
Haplotypes
Agar
Immunization
Morbidity
T-Lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid. / Worgall, Stefan; Krause, Anja; Rivara, Michael; Hee, Kyung Kim; Vintayen, Enrico V.; Hackett, Neil R.; Roelvink, Peter W.; Bruder, Joseph T.; Wickham, Thomas J.; Kovesdi, Imre; Crystal, Ronald.

In: Journal of Clinical Investigation, Vol. 115, No. 5, 01.05.2005, p. 1281-1289.

Research output: Contribution to journalArticle

Worgall, S, Krause, A, Rivara, M, Hee, KK, Vintayen, EV, Hackett, NR, Roelvink, PW, Bruder, JT, Wickham, TJ, Kovesdi, I & Crystal, R 2005, 'Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid', Journal of Clinical Investigation, vol. 115, no. 5, pp. 1281-1289. https://doi.org/10.1172/JCI200523135
Worgall, Stefan ; Krause, Anja ; Rivara, Michael ; Hee, Kyung Kim ; Vintayen, Enrico V. ; Hackett, Neil R. ; Roelvink, Peter W. ; Bruder, Joseph T. ; Wickham, Thomas J. ; Kovesdi, Imre ; Crystal, Ronald. / Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 5. pp. 1281-1289.
@article{e5f228915aa6408686df7a843f3d3db6,
title = "Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid",
abstract = "Pseudomonas aeruginosa is an important opportunistic pathogen that can cause chronic and often life-threatening infections of the respiratory tract, particularly in individuals with cystic fibrosis (CF). Because infections with P. aeruginosa remain the major cause of the high morbidity and mortality of CF, a vaccine against P. aeruginosa would be very useful for preventing this disorder. The outer membrane protein F (OprF) of P. aeruginosa is a promising vaccine candidate and various B cell epitopes within OprF have been identified. Given that adenovirus (Ad) vectors have strong immunogenic potential and can function as adjuvants for genetic vaccines, the present study evaluates the immunogenic and protective properties of a novel replication-deficient Ad vector in which the Ad hexon protein was modified to include a 14-amino acid epitope of P. aeruginosa OprF (Epi8) in loop 1 of the hypervariable region 5 of the hexon (AdZ.Epi8). Immunization of C57BL/6 mice with AdZ.Epi8 resulted in detectable serum anti-P. aeruginosa and anti-OprF humoral responses. These responses were haplotype dependent, with higher serum anti-OprF titers in CBA mice than in BALB/c or C57BL/6 mice. AdZ.Epi8 induced Epi8-specific IFN-γ-positive CD4 and CD8 T cell responses and resulted in protection against a lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeated administration of AdZ.Epi8 resulted in boosting of the anti-OprF humoral and anti-Epi8 cellular response, whereas no boosting effect was present in the response against the transgene β-galactosidase. These observations suggest that Ad vectors expressing pathogen epitopes in their capsid will protect against an extracellular pathogen and will allow boosting of the epitope-specific humoral response with repeated administration, a strategy that should prove useful in developing Ad vectors as vaccines where humoral immunity will be protective.",
author = "Stefan Worgall and Anja Krause and Michael Rivara and Hee, {Kyung Kim} and Vintayen, {Enrico V.} and Hackett, {Neil R.} and Roelvink, {Peter W.} and Bruder, {Joseph T.} and Wickham, {Thomas J.} and Imre Kovesdi and Ronald Crystal",
year = "2005",
month = "5",
day = "1",
doi = "10.1172/JCI200523135",
language = "English",
volume = "115",
pages = "1281--1289",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",

}

TY - JOUR

T1 - Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid

AU - Worgall, Stefan

AU - Krause, Anja

AU - Rivara, Michael

AU - Hee, Kyung Kim

AU - Vintayen, Enrico V.

AU - Hackett, Neil R.

AU - Roelvink, Peter W.

AU - Bruder, Joseph T.

AU - Wickham, Thomas J.

AU - Kovesdi, Imre

AU - Crystal, Ronald

PY - 2005/5/1

Y1 - 2005/5/1

N2 - Pseudomonas aeruginosa is an important opportunistic pathogen that can cause chronic and often life-threatening infections of the respiratory tract, particularly in individuals with cystic fibrosis (CF). Because infections with P. aeruginosa remain the major cause of the high morbidity and mortality of CF, a vaccine against P. aeruginosa would be very useful for preventing this disorder. The outer membrane protein F (OprF) of P. aeruginosa is a promising vaccine candidate and various B cell epitopes within OprF have been identified. Given that adenovirus (Ad) vectors have strong immunogenic potential and can function as adjuvants for genetic vaccines, the present study evaluates the immunogenic and protective properties of a novel replication-deficient Ad vector in which the Ad hexon protein was modified to include a 14-amino acid epitope of P. aeruginosa OprF (Epi8) in loop 1 of the hypervariable region 5 of the hexon (AdZ.Epi8). Immunization of C57BL/6 mice with AdZ.Epi8 resulted in detectable serum anti-P. aeruginosa and anti-OprF humoral responses. These responses were haplotype dependent, with higher serum anti-OprF titers in CBA mice than in BALB/c or C57BL/6 mice. AdZ.Epi8 induced Epi8-specific IFN-γ-positive CD4 and CD8 T cell responses and resulted in protection against a lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeated administration of AdZ.Epi8 resulted in boosting of the anti-OprF humoral and anti-Epi8 cellular response, whereas no boosting effect was present in the response against the transgene β-galactosidase. These observations suggest that Ad vectors expressing pathogen epitopes in their capsid will protect against an extracellular pathogen and will allow boosting of the epitope-specific humoral response with repeated administration, a strategy that should prove useful in developing Ad vectors as vaccines where humoral immunity will be protective.

AB - Pseudomonas aeruginosa is an important opportunistic pathogen that can cause chronic and often life-threatening infections of the respiratory tract, particularly in individuals with cystic fibrosis (CF). Because infections with P. aeruginosa remain the major cause of the high morbidity and mortality of CF, a vaccine against P. aeruginosa would be very useful for preventing this disorder. The outer membrane protein F (OprF) of P. aeruginosa is a promising vaccine candidate and various B cell epitopes within OprF have been identified. Given that adenovirus (Ad) vectors have strong immunogenic potential and can function as adjuvants for genetic vaccines, the present study evaluates the immunogenic and protective properties of a novel replication-deficient Ad vector in which the Ad hexon protein was modified to include a 14-amino acid epitope of P. aeruginosa OprF (Epi8) in loop 1 of the hypervariable region 5 of the hexon (AdZ.Epi8). Immunization of C57BL/6 mice with AdZ.Epi8 resulted in detectable serum anti-P. aeruginosa and anti-OprF humoral responses. These responses were haplotype dependent, with higher serum anti-OprF titers in CBA mice than in BALB/c or C57BL/6 mice. AdZ.Epi8 induced Epi8-specific IFN-γ-positive CD4 and CD8 T cell responses and resulted in protection against a lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeated administration of AdZ.Epi8 resulted in boosting of the anti-OprF humoral and anti-Epi8 cellular response, whereas no boosting effect was present in the response against the transgene β-galactosidase. These observations suggest that Ad vectors expressing pathogen epitopes in their capsid will protect against an extracellular pathogen and will allow boosting of the epitope-specific humoral response with repeated administration, a strategy that should prove useful in developing Ad vectors as vaccines where humoral immunity will be protective.

UR - http://www.scopus.com/inward/record.url?scp=20944437017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20944437017&partnerID=8YFLogxK

U2 - 10.1172/JCI200523135

DO - 10.1172/JCI200523135

M3 - Article

VL - 115

SP - 1281

EP - 1289

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 5

ER -