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Towards a New Generation of Glycoengineered Pneumococcal Bioconjugate Vaccines

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI131742-01
Agency Tracking Number: R41AI131742
Amount: $210,129.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-02-22
Award End Date (Contract End Date): 2019-02-21
Small Business Information
4447 MCPHERSON AVE
Saint Louis, MO 63108-2505
United States
DUNS: 080343938
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 MARIO FELDMAN
 (314) 747-4473
 mariofeldman@wustl.edu
Business Contact
 CHRISTIAN HARDING
Phone: (843) 331-9533
Email: charding@wusm.wustl.edu
Research Institution
 WASHINGTON UNIVERSITY
 
Campus Box 1054 1 Brookings Drive
SAINT LOUIS, MO 63130-4862
United States

 Nonprofit college or university
Abstract

PROJECT SUMMARY
Pneumococcal pneumonia remains the leading cause of bacterial pneumonia in both children under years of
age and adults over years of age The standard preventative therapy is the conjugate vaccine Prevnar
which consists of an immunogenic carrier protein covalently attached to one of thirteen pneumococcal capsular
polysaccharides Although Prevnar has significantly reduced the burden of pneumococcal disease it only
protects against of the plus pneumococcal serotypes furthermore current methods employed to expand
the serotype coverage are notoriously slow requiring complex synthetic chemistries to link a new
pneumococcal capsular polysaccharide to the immunogenic carrier protein Over the last decade we have
been pioneering an innovative approach to conjugate vaccine development that drastically simplifies the
production of glycoconjugates This glycoengineering strategy consisting of the exploitation of bacterial
glycosylation machineries to generate bioconjugates eliminates the need of intricate chemical conjugation
methods by employing conjugating enzymes to attach polysaccharides to acceptor proteins in Escherichia coli
Two conjugating enzymes PglB and PglL have been commercially utilized to generate bioconjugates as they
are able to transfer a wide variety of polysaccharides to proteins however neither are able to transfer
polysaccharides containing glucose at the reducing end the first sugar of a growing polysaccharide chain
This seemingly simple observation has enormous implications as approximately of pneumococcal
capsules contain glucose at the reducing end Recently we have identified and patented the first conjugating
enzyme that is able to efficiently transfer pneumococcal capsular polysaccharides containing glucose at the
reducing end to an acceptor protein Based on this observation we will couple our novel conjugating enzyme
technology with carrier proteins previously utilized in conjugate vaccine formulations streamlining the
generation of a superior pneumococcal vaccine with broader serotype coverage Importantly our
glycoengineering strategy does not require pathogenic organisms as a source of polysaccharide nor chemical
reactions to link polysaccharides to proteins
The proposed research in this phase I application will focus on Aim glycoengineering three
commercial carrier proteins exotoxin A tetanus toxin fragment C and CRM to contain a modular glycotag
with pneumococcal capsular polysaccharides generating a new bioconjugate vaccine for pneumococcal
serotypes V and b Subsequently Aim we will demonstrate the immunogenicity and efficacy of
our pneumococcal specific bioconjugate vaccine compared to the standard preventative therapy Prevnar
Our next step for phase II funding is to expand the serotype coverage included in our bioconjugate vaccine
develop a large scale purification scheme for obtaining our bioconjugate vaccine as well as pre clinical studies
to further demonstrate the safety potency and efficacy of our next generation glycoengineered pneumococcal
bioconjugate vaccine PROJECT NARRATIVE
The proposal seeks to further develop an innovative technology that can be used to make conjugate vaccines
against pneumococcus with broader coverage without the need of chemical procedures For the first time ever
our group has identified a conjugating enzyme that is able to attach pneumococcal polysaccharides to an
acceptor protein dramatically simplifying the synthesis of protein polysaccharide conjugates In this
application we propose to apply our novel conjugating enzyme technology to carrier proteins previously
utilized in conjugate vaccine formulations streamlining the generation of a superior pneumococcal vaccine with
broader serotype coverage

* Information listed above is at the time of submission. *

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