Vaccines for preventing infection with Pseudomonas aeruginosa in people with cystic fibrosis

Keogan, Mary T.; Johansen, Helle Krogh

doi:10.1002/14651858.cd001399

Cited by 9 publications

(2 citation statements)

References 12 publications

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“…The host response to P. aeruginosa is a complex immune and inflammatory reaction that results in damage to the respiratory tract (1,2). Antibodies as well as cell-mediated immunity seem to be associated with protective immunity, but an efficient vaccine against pulmonary colonization with P. aeruginosa is not yet available (39)(40)(41)(42)(43)(44)(45)(46). Various components of P. aeruginosa have been tested as vaccine candidates in animal studies and humans, among them the outer membrane protein OprF.…”

Section: Figurementioning

confidence: 99%

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

Worgall¹,

Krause²,

Rivara³

et al. 2005

J. Clin. Invest.

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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.

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Section: Figurementioning

confidence: 99%

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

Worgall¹,

Krause²,

Rivara³

et al. 2005

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The host response to P. aeruginosa is a complex immune and inflammatory reaction that results in damage to the respiratory tract (1, 2). Antibodies as well as cell-mediated immunity seem to be associated with protective immunity, but an efficient vaccine against pulmonary colonization with P. aeruginosa is not yet available (39)(40)(41)(42)(43)(44)(45)(46). Various components of P. aeruginosa have been tested as vaccine candidates in animal studies and humans, among them the outer membrane protein OprF.…”

Section: Figurementioning

confidence: 99%

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

Worgall¹,

Krause²,

Rivara³

et al. 2005

J. Clin. Invest.

View full text Add to dashboard Cite

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

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Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

Johansen

Gøtzsche²

2015

Cochrane Database of Systematic Reviews

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Vaccines for preventing infection with Pseudomonas aeruginosa in people with cystic fibrosis

Cited by 9 publications

References 12 publications

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

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

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

Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

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