Abstract
BackgroundVirus-specific cellular immune responses play a critical role in virus clearance during acute or chronic HBV infection. Currently, the commercially available HBV vaccine is combined with alum adjuvant, which stimulates mainly Th2 immune responses. Therefore, development of new therapeutic HBV vaccine adjuvants and immune strategies that also promote Th1 and CTL responses is urgently needed.Methodology/Principal findingsTo improve the immunity induced by the novel HBSS1 HBV vaccine, we evaluated the ability of adjuvants, including alum, CpG and polyriboinosinic polyribocytidylic acid [poly(I:C)], to enhance the response when boosted with the recombinant adenoviral vector vaccine rAdSS1. The immune responses to different adjuvant combinations were assessed in C57BL/6 mice by enzyme-linked immunosorbent assay (ELISA), ELISpot and cytokine release assays. Among the combinations tested, a HBV protein particle vaccine with CpG/alum and poly(I:C)/alum priming combinations accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody) titres with a Th1 bias. After boosting with recombinant adenoviral vector vaccine rAdSS1, both groups produced a strong multi-antigen (S and PreS1)-specific cellular immune response. HBSS1 immunisation with poly(I:C)/alum priming also generated high-level CD4+ and CD8+ T cell responses in terms of Th1 cytokines (IFN-γand IL-2).ConclusionsThe protein-vaccine HBSS1 with mixed poly(I:C)/alum adjuvant priming, followed by a rAdSS1 vaccine boost, maximises specific antibody and Th1-biased cellular immune responses. This regime might prove useful in the development of HBV therapeutic vaccines. Furthermore, this promising strategy might be applied to vaccines against other persistent infections, such as human immunodeficiency virus and tuberculosis.
Highlights
Hepatitis B virus (HBV) infection is a public health problem
The protein-vaccine HBSS1 with mixed poly(I:C)/alum adjuvant priming, followed by a rAdSS1 vaccine boost, maximises specific antibody and Th1-biased cellular immune responses. This regime might prove useful in the development of HBV therapeutic vaccines
Expression of the target proteins was confirmed by Western blot using a rabbit anti-PreS1 polyclonal antibodies, which recognize HBSS1 protein with 3 bands of different molecular weights, two of bands were showed as previous report size(,24 kD,27 kD),the third band(,26 kD) might represent another glycoylated form of HBSS1 protein produced in this system(Figure 1B)
Summary
Hepatitis B virus (HBV) infection is a public health problem. Over 350 million people globally are chronically infected with HBV, and about 25% of those die from chronic active hepatitis, cirrhosis, or hepatocellular carcinoma [1,2,3]. Interferon-a and nucleoside analogues are the two main types of antiviral medicines used to treat chronic HBV. The currently available recombinant subunit HBV vaccines are safe and efficacious for prevention; due to the lack of suitable adjuvants, they have no effect on the clearance of HBV among existing HBV carriers or patients. There is a pressing need to develop a therapeutic vaccine to prevent, control or cure chronic HBV infection [5]. Virus-specific cellular immune responses play a critical role in virus clearance during acute or chronic HBV infection. The commercially available HBV vaccine is combined with alum adjuvant, which stimulates mainly Th2 immune responses. Development of new therapeutic HBV vaccine adjuvants and immune strategies that promote Th1 and CTL responses is urgently needed
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