Methods of treating or preventing an infectious disease using an immunogenic conjugate of a gram-negative bacterial autoinducer molecule or antibodies that immunospecifically bind a gram-negative bacterial autoinducer molecule
申请人:Kende S. Andrew
公开号:US20070231839A1
公开(公告)日:2007-10-04
The present invention relates to an immunogenic conjugate comprising a carrier molecule coupled to an autoinducer of a Gram negative bacteria The immunogenic conjugate, when combined with a pharmaceutically acceptable carrier, forms a suitable vaccine for mammals to prevent infection by the Gram negative bacteria The immunogenic conjugate is also used to raise and subsequently isolate antibodies or binding portions thereof which are capable of recognizing and binding to the autoinducer. The antibodies or binding portions thereof are utilized in a method of treating infections, a method of inhibiting autoinducer activity, and in diagnostic assays which detect the presence of autoinducers or autoinducer antagonists in fluid or tissue samples.
TABLE OF CONTENTS
Page
1. FIELD OF THE INVENTION
1
2. BACKGROUND OF THE INVENTION
1
3. SUMMARY OF THE INVENTION
4
4. BRIEF DESCRIPTION OF THE DRAWINGS
7
5. DETAILED DESCRIPTION OF THE INVENTION
7
5.1 Isolation and Synthesis of Homoserine Lactones
7
5.2 Bacterial Autoinducer Conjugation to a Carrier
17
5.3 Generation of Antibodies to BAI Immunogenic conjugates
19
5.4 Therapeutic Uses of Immunogenic conjugates
22
or Antibodies Thereto
5.4.1 Administration and Formulation
22
5.4.2 Effective Dose
25
5.5 Diagnostic Methods
27
6. EXAMPLE: SYNTHESIS
32
Preparation of Compound C
32
Preparation of Compound D
32
Preparation of Compound 5
32
Preparation of Compound 6
33
Preparation of Compound 7
33
Preparation of Compound 8
33
Preparation of Compound 10
34
Preparation of Compound 11
34
Preparation of Compound 13
35
Preparation of Compound 12
35
Preparation of Compound 14
35
Preparation of Compound 15
36
Preparation of Compound 17
36
Preparation of Compound 21
37
Preparation of Compound 22
37
Preparation of Compound 24
38
Preparation of Compound 25
38
Preparation of Compound 27
38
Preparation of Compound 29
39
7. EXAMPLE: PRODUCTION OF BAI ANTIBODIES
39
7.1 PAI'S Role In Virulence
39
7.2 Anti-PAI Polyclonal Antibodies
40
7.3 Neutralization of PAI With Antibodies
40