Immunization With a Subunit Hepatitis C Virus Vaccine Elicits Pan-Genotypic Neutralizing Antibodies and Intrahepatic T-Cell Responses in Nonhuman Primates.

TitleImmunization With a Subunit Hepatitis C Virus Vaccine Elicits Pan-Genotypic Neutralizing Antibodies and Intrahepatic T-Cell Responses in Nonhuman Primates.
Publication TypeJournal Article
Year of Publication2017
AuthorsLi, D, Wang, X, von Schaewen, M, Tao, W, Zhang, Y, Heller, B, Hrebikova, G, Deng, Q, Sun, Q, Ploss, A, Zhong, J, Huang, Z
JournalJ Infect Dis
Volume215
Issue12
Pagination1824-1831
Date Published2017 06 15
ISSN1537-6613
KeywordsAdjuvants, Immunologic, Animals, Antibodies, Neutralizing, Enzyme-Linked Immunosorbent Assay, Female, Genotype, Hepacivirus, Hepatitis C, Hepatitis C Antibodies, Humans, Immunization, Leukocytes, Mononuclear, Liver, Macaca mulatta, Male, T-Lymphocytes, Viral Hepatitis Vaccines
Abstract

<p><b>Background: </b>The global control of hepatitis C virus (HCV) infection remains a great burden, owing to the high prices and potential drug resistance of the new direct-acting antivirals (DAAs), as well as the risk of reinfection in DAA-cured patients. Thus, a prophylactic vaccine for HCV is of great importance. We previously reported that a single recombinant soluble E2 (sE2) vaccine produced in insect cells was able to induce broadly neutralizing antibodies (NAbs) and prevent HCV infection in mice. Here the sE2 vaccine was evaluated in non-human primates.</p><p><b>Methods: </b>Rhesus macaques were immunized with sE2 vaccine in combination with different adjuvants. Vaccine-induced NAbs in antisera were tested for neutralization activities against a panel of cell culture-derived HCV (HCVcc), while T-cell responses were evaluated in splenocytes, peripheral blood mononuclear cells, and hepatic lymphocytes.</p><p><b>Results: </b>sE2 is able to elicit NAbs against HCVcc harboring structural proteins from multiple HCV genotypes in rhesus macaques. Moreover, sE2-immunized macaques developed systemic and intrahepatic memory T cells specific for E2. A significant correlation between the sE2-specific immunoglobulin G titers and neutralization spectrum was observed, highlighting the essential role of sE2 immunogenicity on achieving broad NAbs.</p><p><b>Conclusions: </b>sE2 is a promising HCV vaccine candidate that warrants further preclinical and clinical development.</p>

DOI10.1093/infdis/jix180
Alternate JournalJ Infect Dis
PubMed ID28398489
PubMed Central IDPMC5853543
Grant ListR01 AI079031 / AI / NIAID NIH HHS / United States
R01 AI107301 / AI / NIAID NIH HHS / United States