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

• DOI: 10.1073/pnas.2112008119
• Publication Date: 2022-03-09T19:09:26Z
• Authors: Ruixue Wang; Saori Suzuki; Johnathan D. Guest; Brigitte Heller; Maricar Almeda; Alexander K. Andr...; Alexander Marin; Roy A. Mariuzza; Zhen-Yong Keck; Steven K. H. Foung; Abdul S. Yunus; Brian G. Pierce; Eric A. Toth; Alexander Ploss; Thomas R. Fuerst
• Keywords: Viral Hepatitis Vaccines; 0301 basic medicine; Biological Sciences; Hepatitis C Antibodies; Hepatitis C; 3. Good health; Mice; 03 medical and health sciences; Immunogenicity, Vaccine; Viral Envelope Proteins; Animals; Protein Multimerization; Broadly Neutralizing Antibodies

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