Mucosal vaccination with a recombinant OprF-I vaccine of<i>Pseudomonas aeruginosa</i>in healthy volunteers: comparison of a systemic vs. a mucosal booster schedule

Göcke, Kerstin; Baumann, Ulrich; Hagemann, H; Gabelsberger, Josef; Hahn, Heinz; Freihorst, Joachim; Specht, B U von

doi:10.1016/s0928-8244(03)00094-4

Cited by 36 publications

(26 citation statements)

References 33 publications

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“…An enhanced mucosal antibody response and protection at both the induction site as well as at distant sites, together with an augmented systemic immunogenicity, have been reported in other studies of the nasal application of recombinant attenuated Salmonella or protein in mice (19,23,36). In our own clinical experience with a nasal gel vaccine with the recombinant OprF-OprI protein of P. aeruginosa, the serum antibody response also increased with use of a systemic booster schedule in humans (13). Our data suggest that the primary vaccination determines the type of response to the booster vaccination in terms of homing pattern, IgG-IgA distribution, and TH1-TH2 balance.…”

Section: Vol 72 2004supporting

confidence: 77%

“…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%

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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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Section: Vol 72 2004supporting

confidence: 77%

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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“…The incorporation of an epitope against the P. aeruginosa OprF protein into loop 1 of hypervariable region 5 of the Ad hexon protein has been shown to induce antiepitope humoral and cellular immunity to protect against infections with P. aeruginosa in a murine model (55). The advantage of incorporating an epitope into the Ad hexon is that this strategy enables repeat administration with the same vector to boost the antiepitope immunity (12,16,17). Another Ad capsid modification to circumvent preexisting anti-Ad immunity has been the use of hexon loops or fibers derived from different Ad serotypes (38,43).…”

Section: Discussionmentioning

confidence: 99%

Protective Immunity toPseudomonas aeruginosaInduced with a Capsid-Modified Adenovirus ExpressingP. aeruginosaOprF

Worgall

Krause²,

Qiu³

et al. 2007

J Virol

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This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1 ؊ E3 ؊ adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.

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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%

“…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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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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Mucosal vaccination with a recombinant OprF-I vaccine ofPseudomonas aeruginosain healthy volunteers: comparison of a systemic vs. a mucosal booster schedule

Cited by 36 publications

References 33 publications

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

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

Protective Immunity toPseudomonas aeruginosaInduced with a Capsid-Modified Adenovirus ExpressingP. aeruginosaOprF

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

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