Isolated FrpB nucleic acid molecule

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C435S069100

Reexamination Certificate

active

06265567

ABSTRACT:

BACKGROUND OF THE INVENTION
FrpB has been described as a 70 kD major iron-regulated, outer-membrane protein common to
N. gonorrhoeae
and
N. menigitidis
(16, 21). The iron uptake systems of
N. meningitidis
and
N. gonorrhoeae
are similar (3,17).
Previous studies showed that FrpB is surface exposed and immunogenic in vivo (1,16, 41). Polyclonal and some monoclonal anti-FrpB antibodies recognize the denatured protein on Western blots of nearly all gonococcal and meningococcal isolates tested (16 and this invention). Other monoclonal antibodies directed against meningococcal FrpB are bactericidal and strain specific (41). Nevertheless, the size of FrpB appears to be well conserved.
FrpB is useful as a vaccine because of its surface exposure (1,16,41), partial antigenic conservation (8,16), and susceptibility to attack by bactericidal antibodies (41). The cloning and sequencing of the frpB gene of this invention has made possible the production of a vaccine against infection in mammals by
N. gonorrhoeae
or
N. meningitidis.
SUMMARY OF THE INVENTION
The present invention provides an isolated nucleic acid molecule that encodes an amino acid sequence comprising a FrpB protein.
The invention also provides a method of producing a vaccine composition that protects a mammal from infection by
N. gonorrhoeae
or
N. meningitidis
comprising combining the FrpB protein encoded by the isolated nucleic acid of the invention with a pharmaceutically acceptable carrier.
The invention further provides a vaccine composition capable of protecting a mammal against infection by
N. gonorrhoeae
or
N. meningitidis
, the vaccine composition comprising the FrpB protein encoded by the isolated nucleic acid of the invention and a pharmaceutically acceptable carrier.
In addition, the invention provides antibodies directed to an epitope of the FrpB protein encoded by the isolated nucleic acid sequence of the invention.
The invention also provides a method of detecting an antibody specific for
N. gonorrhoeae
or
N. meningitidis
in a sample comprising contacting the sample with a FrpB protein encoded by the isolated nucleic acid sequence of the invention under conditions to form a complex between the polypeptide and the antibody; and detecting any complex so formed.
Furthermore, the invention provides a method of treating a mammal infected by
N. gonorrhoeae
or
N. meningitidis
comprising administering to the mammal an antibody of the invention, wherein the antibody is directed to an epitope of an
N. gonorrhoeae
or
N. meningitidis
FrpB protein.


REFERENCES:
Ley et al. “Sequence variability of FrpB, a major iron-regulated outer-membrane protein in the pathogenic neisseriae”, Microbiology. vol. 142, pp 3269-3274, 1996.*
Pettersson et al. “Molecular characterization of the FrpB, the 70-Kilodalton iron-regulated outer membrane protein ofneisseria meningitidis”, Infection and Immunity. vol. 63, No. 10, pp 4181-4184, Oct. 1995.*
Dempsey et al Journal of BActeriology vol. 173 No. 17 5476-5486, Sep. 1991.*
Beucher, M. Dissertation Abstracts International vol. 56, No. 2 p. 624-B, Aug. 1995.*
Sambrook et al Molecular Cloning A Laboratory Manual, Second Edition Cold Spring Harbor Press, pp. 8.46,8.50, 8.51, 1989.*
Dyer et al, Infection and Immunity vol. 56, No. 4, 977-983, Apr. 1988.*
Beucher et al Journal of Bacteriology vol. 177 No. 8 2041-2149, Apr. 1995.*
Ala'Aldeen et al Vaccine vol. 12 No. 6 535-541, 1994.*
Biotechnology Newswatch p. 12 Vaccines for Sexually Transmitted diseases advancing but slowly, May 1995.*
van der Ley et al Microbiology vol. 142 3269-3274, 1996.*
Pettersson et al Infection and Immunity vol. 63, No. 10 4181-4184, Oct. 1995.*
LAzar et al Molecular and Cellular Biology vol. 8 No. 3 1247-1252, Mar. 1988.*
Burgess et al Journal of Cell biology vol. 111 2129-2138, Nov. 1990.

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