Title | Induction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1E2 heterodimer as a vaccine candidate. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Wang, 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 |
Journal | Proc Natl Acad Sci U S A |
Volume | 119 |
Issue | 11 |
Pagination | e2112008119 |
Date Published | 2022 Mar 15 |
ISSN | 1091-6490 |
Keywords | Animals, 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> |
DOI | 10.1073/pnas.2112008119 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 35263223 |
PubMed Central ID | PMC8931252 |
Grant List | R01 AI107301 / AI / NIAID NIH HHS / United States R01 AI132213 / AI / NIAID NIH HHS / United States R21 AI154100 / AI / NIAID NIH HHS / United States |