Novel adeno‑associated virus‑based genetic vaccines encoding hepatitis C virus E2 glycoprotein elicit humoral immune responses in mice

Autor: Haiyang Qu, Lingling Niu, Hairong Zhang, Heng He, Fengqin Zhu, Yibo Wang, Honglu Xue, Zhen Xu, Dehuai Jing
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
hepatitis C virus
Cancer Research
viruses
Hepacivirus
medicine.disease_cause
Biochemistry
Mice
0302 clinical medicine
Viral Envelope Proteins
Vaccines
DNA
Medicine
Neutralizing antibody
Adeno-associated virus
biology
Immunogenicity
Articles
Dependovirus
Middle Aged
Recombinant Proteins
prophylactic vaccine
Oncology
030220 oncology & carcinogenesis
glycoprotein E2
Molecular Medicine
Female
Antibody
Adult
Viral Hepatitis Vaccines
Hepatitis C virus
Genetic Vectors
adeno-associated virus
03 medical and health sciences
Antigen
Immunity
Genetics
Animals
Humans
Molecular Biology
business.industry
Immune Sera
Hepatitis C Antibodies
Hepatitis C
Chronic
Virology
Antibodies
Neutralizing
Immunity
Humoral
Mice
Inbred C57BL
030104 developmental biology
HEK293 Cells
Immunization
biology.protein
business
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
Popis: Hepatitis C virus (HCV) infection remains a major public health issue despite the introduction of several direct-acting antiviral agents (DAAs), with some 185 million individuals infected with HCV worldwide. There is an urgent need for an effective prophylactic HCV vaccine. In the present study, we constructed genetic vaccines based on novel recombinant adeno-associated viral (rAAV) vectors (AAV2/8 or AAV2/rh32.33) that express the envelope glycoprotein E2 from the HCV genotype 1b. Expression of HCV E2 protein in 293 cells was confirmed by western blot analysis. rAAV2/8.HCV E2 vaccine or rAAV2/rh32.33.HCV E2 vaccine was intramuscularly injected into C57BL/6 mice. HCV E2-specific antigen was produced, and long-lasting specific antibody responses remained detectable XVI weeks following immunization. In addition, the rAAV2/rh32.33 vaccine induced higher antigen-specific antibody levels than the rAAV2/8 vaccine or AAV plasmid. Moreover, both AAV vaccines induced neutralizing antibodies against HCV genotypes 1a and 1b. Finally, it is worth mentioning that neutralizing antibody levels directed against AAV2/rh32.33 were lower than those against AAV2/8 in both mouse and human serum. These results demonstrate that AAV vectors, especially the AAVrh32.33, have particularly favorable immunogenicity for development into an effective HCV vaccine.
Databáze: OpenAIRE
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