Immunogenic hybrid protein OprF-Oprl derived from...

Details Immunogenic hybrid protein OprF-Oprl derived from... Immunogenic hybrid protein OprF-Oprl derived from...

1999-03-10

2001-10-09

Graser, Jennifer E. (Department: 1645)

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

C435S069700, C435S320100, C435S071100, C435S071200, C435S252300, C536S023700, C536S023400, C424S260100

Reexamination Certificate

active

06300102

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a hybrid protein comprising the
Pseudomonas aeruginosa
outer membrane protein I (OprI or OMPI) which is fused with its amino terminal end to the carboxy-terminal end of a carboxy-terminal portion of the
Pseudomonas aeruginosa
outer membrane protein F (OprF or OMPF), as well as to monoclonal or polyclonal antibodies against this hybrid protein. Both, the hybrid protein and the antibodies directed to the hybrid protein confer protection against an infection by
Pseudomonas aeruginosa
to laboratory animals or man.
BACKGROUND OF THE INVENTION
Pseudomonas aeruginosa
is an opportunistic gram-negative pathogen. It represents a major course of hospital-aquired infections, especially in burnt and other immuno-compromised patients, including transplant or cancer patients. Therefore, it is regarded as a “problem microbe” in human medicine.
Many efforts have been made so far in order to develop a vaccine against
Pseudomonas aeruginosa.
For example, in the EP-0 297 291 the complete amino acid-sequence of the outer membrane protein F, as well as the nucleotide sequence coding for OprF is disclosed. In the EP-0 357 024 the complete amino acid sequence of the outer membrane protein I and, additionally, the nucleotide sequence coding for OprI is shown. Furthermore, with both proteins it was shown that they may be useful for conferring immunoprotection against Pseudomonas aeruginosa to an animal or human proband. However, improvement of procedures of vaccination against a lethal
Pseudomonas aeruginosa
infection is still an object.
SUMMARY OF THE INVENTION
Surprisingly, it was found by the inventors that a hybrid protein, wherein OprI is linked with its N-terminal end to a C-terminal portion of OprF is significantly more immunogenic than fusion proteins only comprising OprI or OprF or mixtures of the latter fusion proteins.


REFERENCES:
patent: 5338669 (1994-08-01), Gillies
patent: 0 297 291 B1 (1989-01-01), None
patent: 0 357 024 A2 (1990-03-01), None
patent: WO 93/24636 (1993-12-01), None
patent: 93/24636 (1993-12-01), None
GenCore Accession #M25761. Duchene et al., 1989.*
GenCore Accession #Q84578. Cornelis et al., 1995.*
GenCore Accession #N82023. Domedy et al., 1987.*
Duchene et al. J. Bacteriol. 170: 155-162, 1988.*
Martin et al. FEMS Microbiol. Lett. 113(3): 261-266, 1993.*
Duchene et al. J.Bacteriol. Aug. 1989. 171: 4130-4137, 1989.*
Baldari et al., “A Novel Leader Peptide Which Allows Efficient Secretion of a Fragment of Human Interleukin 1&bgr; inSaccharomyces cerevisiae,”Embo J.6(1):229-234 (1987).
Duchene et al., “Sequence and Transcriptional Start Site of thePseudomonas aeruginosaOuter Membrane Porin Protein F Gene,”J. Bacteriol. 170(1):155-162 91988).
Duchene et al., “Pseudomonas aeruginosaOuter Membrane Viproprotein I Gene: Molecular Cloning, Sequence, and Expression inEscherichia coli,”J. Bacteriol. 171(8):4130-4137 (1989).
Finke et al., “Protection Against ExperimentalPseudomonas aeruginosaInfection by RecombinantP. aeruginosaLipoprotein I Expressed inEscherichia coli,”Infect. Immun. 58(7):2241-2244 (1990).
Finke et al., “Protection of Immunosuppressed Mice Against Infection WithPseudomonas aeruginosaby RecombinantP. aeruginosaLipoprotein I and Lipoprotein I-Specific Monoclonal Antibodies,”Infect. Immun. 59(4):1251-1254 (1991).
Finnen, Renee L., et al., “Anaylsis of thePseudomonas aeruginosaMajor Outer Membrane Protein OprF by Use of Truncated OprF Derivatives and Monoclonal Antibodies,”J. Bacteriol. 174(15):4977-4985 (1992).
Horton et al., “Engineering Hybrid Genes Without the Use of Restriction Enzymes: Gene Splicing by Overlap Extension,”Gene77:61-68 (1989).
Hughes et al., “Synthetic Peptides Representing Epitopes of Outer Membrane Protein F ofPseudomonas aeruginosaThat Elicit Antibodies Reactive With Whole Cells of Heterologous Immunotype Strains ofP. aeruginosathat elicit Antibodies Reactive With Wholw Cells of Heterologous Immunotype Strains ofP. aeruginosa,”Infec. Immun. 60(9):3497-3503 (1992).
Johnson et al., “Improved Technique Utilizing Nonfat Dry Milk for Analysis of Proteins and Nucleic Acids Transferred to Nitrocellulose,”Gene Anal. Techn. 1:3-8 (1984).
Roussilhon et al., “Responses of T Cells From Sensitized Donors to Recombinant and Synthetic Peptides corresponding to Sequences of thePlasmodium falciparumSERP Antigen,”Immunol. Lett. 25:149-154 (1990).
Schorr et al., “Surface Expression of Malarial Antigens inSalmonella typhimurium: Induction of Serum Antibody Response Upon Oral Vaccination of Mice,”Vaccine9:675-681 (1991).
Von Specht et al., “Outer Membrane Proteins ofPseudomonas aeruginosaas Vaccine Candidates,”Behring Inst. Mitt., vol. 95:85-96.
European Patent Office Form 1503.

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