Safety and immunogenicity of an intranasal Pseudomonas aeruginosa hybrid outer membrane protein F-I vaccine in human volunteers

Larbig, Michael; Mansouri, Erfan; Freihorst, Joachim; Tümmler, Burkhard; Köhler, Gabriele; Domdey, Horst; Knapp, Bernhard; Hungerer, Klaus-Dieter; Hundt, Erika; Gabelsberger, Josef; Specht, B U von

doi:10.1016/s0264-410x(00)00550-8

Cited by 52 publications

(34 citation statements)

References 34 publications

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“…Antibodies against OprF are associated with protection in animal models and human infection and are present in the serum of individuals with CF chronically colonized with P. aeruginosa in the lung (22-28, 51, 52). Immunization with recombinant OprF has been shown to generate protective immune responses, and recombinant OprF is being tested as a vaccine candidate against infections with P. aeruginosa in animals and humans (22)(23)(24)(25)(26)(27)(28). Genetic immunization with DNA encoding an OprF/OprI hybrid via a gene gun in mice resulted in humoral immunity against P. aeruginosa (29).…”

Section: Figurementioning

confidence: 99%

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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%

“…OprF has been shown to be immunogenic in laboratory animals and humans, and the sequence of OprF suggests that there are several extracellular loops that serve as good B cell epitopes ( Figure 1) (21)(22)(23)(24)(25)(26)(27)(28)(29). The Ad hexon is the most abundant immunogenic of the Ad capsid proteins (30)(31)(32)(33).…”

Section: Introductionmentioning

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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“…[17][18][19] Because of considerable inter-individual differences in immune response against the IC43 vaccine, no definitive doses have yet been established. 18,19 A possible enhancement of antibody induction using aluminum hydroxide adjuvanted as shown for other vaccines 19 has not yet been tested for IC43 and data about the safety and tolerability of adjuvanted vs. not-adjuvanted IC43 do not exist .…”

Section: Introductionmentioning

confidence: 99%

A randomized, placebo-controlled phase I study assessing the safety and immunogenicity of aPseudomonas aeruginosahybrid outer membrane protein OprF/I vaccine (IC43) in healthy volunteers

Westritschnig

Hochreiter

Wallner

et al. 2013

Human Vaccines & Immunotherapeutics

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“…However, nasal vaccines against various antigens showed variable success. Our own nasal vaccine based on the OprF-OrpI protein from P. aeruginosa showed a relatively weak systemic and mucosal immunogenicity in mice and humans (13,22). Salmonella live vaccines applied in the nose may also raise safety issues with a potential infection of the central nervous system and the paranasal sinuses.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Immunogenicity in the Murine Airway Mucosa with an AttenuatedSalmonellaLive Vaccine Expressing OprF-OprI fromPseudomonas aeruginosa

Arnold¹,

Bumann

Felies³

et al. 2004

Infect Immun

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We constructed an oral live vaccine based on the attenuated aroA mutant Salmonella enterica serovar Typhimurium strain SL3261 expressing outer membrane proteins F and I (OprF-OprI) from Pseudomonas aeruginosa and investigated it in a mouse model. Strains with in vivo inducible protein expression with the P pacC promoter showed good infection rates and immunogenicity but failed to engender detectable antibodies in the lung. However, a systemic booster vaccination following an oral primary immunization yielded high immunoglobulin A (IgA) and IgG antibody levels in both upper and lower airways superior to conventional systemic or mucosal booster vaccination alone. In addition, the proportion of IgG1 and IgG2a antibodies suggested that the systemic booster does not alter the more TH1-like type of response induced by the oral Salmonella primary vaccination. We conclude that an oral primary systemic booster vaccination strategy with an appropriate mucosal vector may be advantageous in diseases with the risk of P. aeruginosa airway infection, such as cystic fibrosis.

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Safety and immunogenicity of an intranasal Pseudomonas aeruginosa hybrid outer membrane protein F-I vaccine in human volunteers

Cited by 52 publications

References 34 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

A randomized, placebo-controlled phase I study assessing the safety and immunogenicity of aPseudomonas aeruginosahybrid outer membrane protein OprF/I vaccine (IC43) in healthy volunteers

Enhanced Immunogenicity in the Murine Airway Mucosa with an AttenuatedSalmonellaLive Vaccine Expressing OprF-OprI fromPseudomonas aeruginosa

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