Nucleic acid sequence and uses thereof

Details Nucleic acid sequence and uses thereof Nucleic acid sequence and uses thereof

1999-08-31

2004-06-29

Devi, S. (Department: 1645)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C536S023100, C536S024320, C424S234100, C424S184100, C424S249100, C435S320100, C435S069100, C435S071100

Reexamination Certificate

active

06756493

ABSTRACT:

1. INTRODUCTION
The present invention relates generally to a polypeptide of Neisseria spp., e.g., of
N. gonorrhoeae
, of approximately 40-55 kD referred to as “NGSP”. The invention encompasses an isolated or purified NGSP polypeptide, fragments thereof and polypeptides derived therefrom (NGSP-derived polypeptides), and methods of making thereof. The invention also encompasses antibodies, including cytotoxic or bactericidal antibodies, that specifically bind the NGSP polypeptide, NGSP-derived polypeptides and/or fragments thereof. The invention further encompasses immunogenic, prophylactic or therapeutic compositions, including vaccines, that comprise NGSP polypeptide, NGSP-derived polypeptides and/or fragments thereof. The invention additionally provides methods of inducing an immune response to
Neisseria gonorrhoeae
in an animal and methods of treating infections in an animal caused by
Neisseria gonorrhoeae
. The invention further provides isolated nucleotide sequences encoding the NGSP polypeptide, NGSP-derived polypeptides and fragments thereof, vectors having said sequences, and host cells containing said vectors.
2. BACKGROUND OF THE INVENTION
Neisseriae are gram-negative diplococci and include but are not limited to
Neisseria ovis, Neisseria lacunata, Neisseria osloensis, Neisseria bovis, Neisseria meningitidis
, and
Neisseria gonorrhoeae
and cause a wide range of infectious diseases.
Although intensely investigated at both the clinical and basic research levels for several decades,
Neisseria gonorrhoeae
remains a sexually transmitted disease (STD) of significant health and economic importance for both the developed as well as the developing world.
N.gonorrhoeae
is the second most common STD in the United States with over 200,000 cases being reported to the Centers for Disease Control and Prevention (CDC) in 1998. Gonococcal infections are usually localized to the mucosal surfaces initially contacted by the pathogen such as the cervix, vagina, urethra, conjunctiva, anorectal area, or the pharyngeal surface and where they can produce a variety of clinical diseases such as cervicitis, urethritis, and conjunctivitis (ophthalmia neonatorum). Acute
N.gonorrhoeae
infections generally elicit classical symptoms and are often accompanied by a purulent lymphocytic discharge at the site of infection. Acute
N.gonorrhoeae
infections can often be treated successfully with appropriate antibiotics many gonococcal infections, in both men and women, remain asymptomatic and can persist for years. While most gonococcal infections remain localized, in some individuals, for reasons yet to be understood, the infection can spread from the primary site of infection and produce a severe disseminated disease such as pelvic inflammatory disease (PID), bacteremia, and arthritis. Besides causing adverse consequences to the urogenital tract, infection with
N.gonorrhoeae
has been shown to facilitate the transmission of the human immunodeficiency virus (HIV).
Fluoroquinolones and broad-spectrum cephalosporins are the most effective antimicrobial agents for the treatment of gonorrhea. However, clinically significant resistance to fluoroquinolones has emerged in
Neisseria gonorrhoeae
and raised concerns regarding the future effectiveness and expense of anti-gonococcal treatment regimens. The development of an effective vaccine that would prevent gonococcal infection and/or significantly reduce the sequelae associated with urogenital infection, especially PID, would provide an attractive and proactive method for combating gonococcal infections. Recent advances in our understanding of gonococcal pathogenesis have provided a foundation for identifying and evaluating antigens, individually and in combination, as potential gonococcal vaccines.
The HtrA protein has been identified as a virulence factor for several bacterial pathogens including,
Yersinia enterocolitica, Brucella abortus
, and
Salmonella typhimurium
. In some but not all organisms HtrA appears to be a stress-responsive protein, possibly contributing to the organisms' survival under oxidative challenge and/or at elevated temperatures. The exact role HtrA plays during the pathogenesis process has not yet been fully defined. Bacteria-host cell interaction and the resulting signal transduction events that are triggered in the pathogen may promote expression of the HtrA protein. The
E. coli
and
N. influenzae
HtrA proteins, including the Hin47 protein described in U.S. Pat. Nos. 5,679,547 and 5,721,115, both of which are incorporated herein by reference in their entireties, have been shown to be serine proteases and possess three relatively conserved domains that house the catalytic residues H, D and S.
HtrA is a virulence factor, having serine protease activity, which has recently been identified as a target for the development of anti-bacterial agents against gram negative bacterial pathogens. (Jones and Hruby, 1998, New targets for antibiotic development: biogenesis of surface adherence structures, DDT Vol. 3(11):495-504; Barrett and Hock, 1998, Two-component signal transduction as a target for microbial anti-infective therapy,
Antimicrobial. Agents and Chemother
. 42(7):1529-1536; Fabret and Hock, 1998, A two-component signal transduction system essential for growth of
Bacillus subtillis
: implications for anti-infective therapy,
J. Bacteriol
., 180(23):63756382).
Citation or identification of any reference in this section or any other section of this application shall not be construed as an indication that such reference is available as prior art to the present invention.
3. SUMMARY OF THE INVENTION
One object of this invention is to identify and provide a novel and highly conserved protein (referred to hereafter and in the claims as “NGSP”) from Neisseria spp., preferably
Neisseria gonorrhoeae, Neisseria ovis, Neisseria lacunata, Neisseria osloensis
, and
Neisseria bovis
. The protein of the present invention has a molecular weight of approximately 40-55 kD, and has limited similarity (~36% identity overall) to the DegP (HtrA) protein of
E. coli
(% identity determined using TBLASTP program (Altschul et al., 1990, J. Molec. Biol. 215:403-10; Altschul et al., 1997, Nuc. Acids Res. 25:3389-3402) with data entered using FASTA format; expect 10 filter default; description 100, alignment) and has not been previously identified in any Neisseria spp. The protein sequence which is another object of this invention has similarity to several DegP/HtrA-like serine proteases from two other bacteria and these sequence homologies have not been previously reported for any Neisseria spp.
The invention is based, in part, on the surprising discovery that
Neisseria gonorrhoeae
, and various strains and cultivars thereof, have a protein, NGSP polypeptide, which is about 40 kD to about 55 kD in molecular weight, preferably about 44 kD to about 53 kD.
The present invention encompasses the NGSP polypeptide of
Neisseria gonorrhoeae
and other Neisseria spp, including but not limited to,
Neisseria ovis, Neisseria lacunata, Neisseria osloensis
, and
Neisseria bovis
, having a molecular weight, as determined from the deduced amino acid sequence, of 40 kD to about 55 kD, in isolated or recombinant form. A homologous protein, NMASP, from
Neisseria meningitidis
, is described and claimed in copending application of Applicants entitled “
Neisseria meningitidis
Polypeptide, Gene Sequence And Uses Thereof” (Application No.: 09/388,089) filed on even date herewith, which is hereby incorporated by reference in its entirety. The present invention encompasses a purified NGSP polypeptide, polypeptides including fragments, derived therefrom (NGSP-derived polypeptides), and methods for making said polypeptide and derived polypeptides. The invention also encompasses antisera and antibodies, including cytoxic or bactercidal antibodies, which bind to and are specific for the NGSP polypeptide, NGSP-derived polypeptides and/or fragments thereof.
The invention further encompasses pharmaceutical compositions including prophylactic or therapeutic compo

Affiliated with

Also associated with

Rating

Nucleic acid sequence and uses thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Nucleic acid sequence and uses thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleic acid sequence and uses thereof will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3357874