Methods and materials for producing immune responses against polypeptides involved in antibiotic resistance

Inactive Publication Date: 2011-08-04
MAYO FOUND FOR MEDICAL EDUCATION & RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0007]In general, one aspect of this document features a method for inducing an immune response against a polypeptide involved in antibiotic resistance. The method comprises, or consists essentially of, administering to an animal (e.g., a mammal) an amount of the polypeptide or a nucleic acid encoding the polypeptide effective for producing the immune response. The polypeptide can be a blaZ polypeptide, a mecA polypeptide, a whiB7 polypeptide, a tap polypeptide, a RV1473 polypeptide, a katG polypeptide, an inhA polypeptide, a rpoB polypeptide, a gidB polypeptide, a pncA polypeptide, an embB polypeptide, or a gyrA polypeptide. The antibiotic resistance can be penicillin-resistance. The antibiotic resistance can be methicillin-resistance. The antibiotic resistance can be vancomycin-resistance. The animal can be a human. The method can comprise administering the polypeptide to the animal. The method can comprise administering the nucleic acid to the animal. The nucleic acid can be a viral vector encoding the polypeptide. The viral vector can be an adenoviral, vaccinia viral, measles, or adeno-associated virus vector. The immune response can reduce the severity of an infection within said animal. The infection can be a Mycobacterium tuberculosis infection. The infection can be a Staphylococcus aureus infection.

Problems solved by technology

However, when pathogens become resistant to effective antibiotics, these normally controlled pathogens can become lethal for the patient and can amplify into to epidemics with no effective treatment.
However, use of antibiotics has selected Mtb that is either multi-drug resistant (MDR) or extensively drug resistant (XDR), both of which are substantially more difficult to treat with multi-drug therapy.

Method used

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  • Methods and materials for producing immune responses against polypeptides involved in antibiotic resistance
  • Methods and materials for producing immune responses against polypeptides involved in antibiotic resistance
  • Methods and materials for producing immune responses against polypeptides involved in antibiotic resistance

Examples

Experimental program
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Effect test

example 1

Plasmids Containing Codon-optimized Antigens

[0029]Codon-optimized sequences for Mtb antigens are obtained from Genscript Corporation (Piscataway, N.J.) or generated using molecular cloning techniques. These sequences are codon-optimized for expression in mammalian cells for use as gene-based vaccines. The following Mtb genes that are expressed by H37Rv, MDR Mtb, or XDR Mtb or those listed in Table 1 that are expressed by H37Rv, MDR Mtb, or XDR Mtb are synthesized and cloned into the pShuttle-CMV plasmid:

[0030]Ag85a: Positive control protective antigen.

[0031]whiB7: Inducer of expression of a regulon of Mtb genes involved in antibiotic resistance (including tap, RV1473, and erm (Morris et al., Proc. Nat'l. Acad. Sci. USA, 102(34):12200-12205 (2005)).

[0032]tap: Drug efflux pump conferring low level resistance to aminoglyosides and tetracycline.

[0033]RV1473: Putative macrolide transporter induced by whiB7 (Morris et al., Proc. Nat'l. Acad. Sci. USA, 102(34):12200-12205 (2005)).

erm: Conf...

example 2

Adenovirus Vectors Containing Codon-Optimized Antigens

[0035]Ad5 vectors are used to generate gene-based vaccines, which are used as an effective vaccine delivery vehicle in mice. Any appropriate vaccine carrier including Bacillus Calmette-Guerin (BCG) or vaccinia is used as a vaccine delivery vehicle in humans. In some cases, the recombinant polypeptides are delivered directly to the mammal (e.g., a human).

[0036]Once the pShuttle-CMV vectors are obtained, they are recombined into the Ad5 genome in bacteria and are used to generate CsCl-purified Ad5 vaccines.

example 3

Codon-Optimized Gene for S. aureus BlaZ

[0037]The following codon-optimized nucleic acid sequence was generated to encode an S. aureus BlaZ polypeptide: AAGGAGCTGAACGACCTGGAGAAGAAGTACAACGCCC-ACATCGGCGTGTACGCCCTGGACACCAAGAGCGGCAAGGAGGTGAAGTTCAACA GCGACAAGCGCTTCGCCTACGCCAGCACCAGCAAGGCCATCAACAGCGCCATCC TGCTGGAGCAGGTGCCCTACAACAAGCTGAACAAGAAGGTGCACATCAACAAGG ACGACATCGTGGCCTACAGCCCCATCCTGGAGAAGTACGTGGGCAAGGACATCA CCCTGAAGGCCCTGATCGAGGCCAGCATGACCTACAGCGACAACACCGCCAACA ACAAGATCATCAAGGAGATCGGCGGCATCAAGAAGGTGAAGCAGCGCCTGAAG GAGCTGGGCGACAAGGTGACCAACCCCGTGCGCTACGAGATCGAGCTGAACTAC TACAGCCCCAAGAGCAAGAAGGACACCAGCACCCCCGCCGCCTTCGGCAAGACC CTGAACAAGCTGATCGCCAACGGCAAGCTGAGCAAGGAGAACAAGAAGTTCCTG CTGGACCTGATGCTGAACAACAAGAGCGGCGACACCCTGATCAAGGACGGCGTG CCCAAGGACTACAAGGTGGCCGACAAGAGCGGCCAGGCCATCACCTACGCCAGC CGCAACGACGTGGCCTTCGTGTACCCCAAGGGCCAGAGCGAGCCCATCGTGCTG GTGATCTTCACCAACAAGGACAACAAGAGCGACAAGCCCAACGACAAGCTGATC AGCGAGACCGCCAAGAGCGTGATGAAGGAGTTC (SEQ ID NO:1). The amino acid sequence encoded by SEQ ID NO...

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Abstract

This document relates to methods and materials for producing immune responses against polypeptides involved in antibiotic resistance. For example, vaccines against polypeptides involved in antibiotic resistance as well as methods for vaccinating mammals against polypeptides involved in antibiotic resistance are provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit of priority from U.S. Provisional Application Ser. No. 61 / 075,881, filed on Jun. 26, 2008.BACKGROUND[0002]1. Technical Field[0003]This document relates to methods and materials for producing immune responses against polypeptides involved in antibiotic resistance. For example, this document provides vaccines against polypeptides involved in antibiotic resistance as well as methods for vaccinating mammals against polypeptides involved in antibiotic resistance.[0004]2. Background Information[0005]For many pathogens, reasonably effective antibiotics and vaccines that can temper or control infections, symptoms, and fatalities are available. However, when pathogens become resistant to effective antibiotics, these normally controlled pathogens can become lethal for the patient and can amplify into to epidemics with no effective treatment. Tuberculosis is an example of this problem. Mycobacterium tuberculosis (Mtb)...

Claims

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Application Information

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IPC IPC(8): A61K39/085A61P31/04
CPCA61K38/164A61K39/04A61K39/085A61K2039/53C12N2710/10034C12N2710/10043C12N2710/10071C12N2800/22A61K2039/5256C12N7/00A61P31/04A61P37/00
Inventor BARRY, MICHAEL A.
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
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