Induction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1E2 heterodimer as a vaccine candidate.

TitleInduction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1E2 heterodimer as a vaccine candidate.
Publication TypeJournal Article
Year of Publication2022
AuthorsWang, R, Suzuki, S, Guest, JD, Heller, B, Almeda, M, Andrianov, AK, Marin, A, Mariuzza, RA, Keck, Z-Y, Foung, SKH, Yunus, AS, Pierce, BG, Toth, EA, Ploss, A, Fuerst, TR
JournalProc Natl Acad Sci U S A
Volume119
Issue11
Paginatione2112008119
Date Published2022 03 15
ISSN1091-6490
KeywordsAnimals, Broadly Neutralizing Antibodies, Hepatitis C, Hepatitis C Antibodies, Immunogenicity, Vaccine, Mice, Protein Multimerization, Viral Envelope Proteins, Viral Hepatitis Vaccines
Abstract

<p>SignificanceHepatitis C virus chronically infects approximately 1% of the world's population, making an effective vaccine for hepatitis C virus a major unmet public health need. The membrane-associated E1E2 envelope glycoprotein has been used in clinical studies as a vaccine candidate. However, limited neutralization breadth and difficulty in producing large amounts of homogeneous membrane-associated E1E2 have hampered efforts to develop an E1E2-based vaccine. Our previous work described the design and biochemical validation of a native-like soluble secreted form of E1E2 (sE1E2). Here, we describe the immunogenic characterization of the sE1E2 complex. sE1E2 elicited broadly neutralizing antibodies in immunized mice, with increased neutralization breadth relative to the membrane-associated E1E2, thereby validating this platform as a promising model system for vaccine development.</p>

DOI10.1073/pnas.2112008119
Alternate JournalProc Natl Acad Sci U S A
PubMed ID35263223
PubMed Central IDPMC8931252
Grant ListR01 AI107301 / AI / NIAID NIH HHS / United States