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Precision Glycoengineering of an HCV Envelope-Based Nanoparticle Vaccine

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI179330-01
Agency Tracking Number: R41AI179330
Amount: $300,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA22-178
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-07-17
Award End Date (Contract End Date): 2024-06-30
Small Business Information
Sykesville, MD 21784-8213
United States
DUNS: 117951622
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (301) 556-9817
Business Contact
Phone: (815) 529-8777
Research Institution
Room 3112 Lee Building 7809 Regents Drive
COLLEGE PARK, MD 20742-0001
United States

 Nonprofit College or University

ABSTRACTGlobally, more than 71 million people are infected with Hepatitis C virus (HCV), with 1-2 million new
infections occurring each year. This major health concern necessitates the development of an effective vaccine.
Since HCV rapidly accumulates mutations, vaccines must elicit the production of broadly neutralizing antibodies
(bnAbs) in a reproducible fashion. The viral envelope E1E2 glycoprotein is a natural target of neutralizing
antibodies. However, two major challenges in production of envelope proteins such as E1E2 are as follows. First,
as the candidate protein advances, it will be critical to obtain a product with stable, reproducible, homogenous
glycoforms that show high potential for yielding a potent and broadly neutralizing antibody response. This
ensures an optimally potent vaccine with comparable efficacy across batches in preclinical and clinical trials, and
makes it easier to retain the glycan profile through manufacturing. However, variation across host cells, even
clones, can lead to substantial variation in glycosylation. Second, upon identifying a glycoform that provides the
desired broadly neutralizing antibody response, it can be difficult to obtain an effective expression host that can
economically produce the vaccine subunit proteins in a functional form. Here we are addressing these challenges
by producing a well-characterized novel native-like secreted E1E2 (sE1E2) complex in a panel of
glycoengineered mammalian cell lines to obtain more homogeneous glycosylation with predictable and defined
structures. After production of preclinical material of all glycoforms, the most effective glycoforms will be identified
by rigorous bioanalytical analysis, coupled to nanoparticles, and subjected to immunological assessment of
polyclonal sera from animals immunized with sE1E2 produced in glycoengineered CHO cell lines, wild-type CHO
cell lines, and HEK 293 and Huh7 control cell lines. Thus, this proposed research will identify optimal glyforms
and help establish a platform cell line for manufacturing an effective pan-HCV vaccine.

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

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