A novel combined vaccine candidate containing epitopes of HCV NS3, core and E1 proteins induces multi-specific immune responses in BALB/c mice.
Hepatitis C virus (HCV) has emerged as the major pathogen of liver disease worldwide. The mechanisms of HCV infection and interaction with a host are poorly understood. What exactly is required for efficient control of HCV infection is largely unknown. Standard treatment combining interferon-alpha (IFN-alpha) and ribavirine is effective in about 50% of the treated patients, however associated with significant toxicity and cost. Therefore, the development of new drugs or vaccines is urgently needed. An efficient vaccine against HCV infection requires induction of broad cellular and humoral immune responses against several viral proteins. We have engineered the combined vaccine candidate mT+mE1, an inclusion of multiple epitopes from HCV NS3, core (C) and E1 proteins. mT contains multiple conserved CD4(+) and CD8(+) T cell epitopes from HCV NS3 and C proteins. mE1 is based on eight dominant neutralizing epitopes of E1 protein from six HCV genotypes. In current study, we showed that immunization with mT+mE1 induced high titers of IgG, IgG1 and IgG2a antibodies to mE1, and high level of NS3- or C-specific CTLs. Furthermore, mT+mE1 elicited a Th1-biased immune response with secretion of high amounts of IFN-gamma, compared with mT alone. Prophylactic as well as therapeutic administration of mT+mE1 in BALB/c mice led to protecting mice against SP2/0 tumor cells expressing HCV NS3 protein. These results suggested that mT+mE1 elicited strong humoral immune responses and multiple specific cellular immune responses. The vaccine candidate is now being tested in pre-clinical trials.
Zeng
Ruihong
R
Department of Immunology, Hebei Medical University, Shijiazhuang 050017, Hebei, PR China. zengruihong@yahoo.com.cn
Li
Guangxue
G
Ling
Shigan
S
Zhang
Heqiu
H
Yao
Zhiyan
Z
Xiu
Bingshui
B
He
Feng
F
Huang
Rui
R
Wei
Lin
L
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000939:Epitopes / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015202:Protein Engineering; D017778:Vaccines, Combined / Q000008:administration & dosage; D014758:Viral Core Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000914:Antibodies, Viral; D000939:Epitopes; D017778:Vaccines, Combined; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C114224:envelope protein E1, GB virus C