Abstract
AimTo investigate the enhancement of humoral immunity when CpG ODN (cytidine phosphate guanosine oligodeoxynucleotides) and aluminium adjuvants are complexed with the HCV (Hepatitis C virus) recombinant immunogen in mice.MethodsAfter immunizing Balb/c mice with the recombination HCV antigen adjuvanted with pUCpGs10 and/or aluminium(antigen+CpG+alum, antigen+CpG, antigen+alum, antigen+PBS), enzyme-linked immunosorbent assay (ELISA) was used to measure the specific serum antibody titers of IgG, to determine the neutralization response to various peptide genotypes, and to determine the concentration of IL-6 and IL-10 in supernatants of in vitro cultured splenic lymphocytes. Enzyme-linked immunospot assay (ELISPOT) was used to quantify the non-specific and specific splenic antibody-secreting cells (ASCs), and flow cytometry (FCM) determined the ratio of different splenic lymphocytes. The serum of rabbits immunized with the recombinant pBVGST/HVR1 antigen immunoprecipitated the HCV isolated from 12 patients' serum.ResultsThe sera antibody titers were 1:51200, 1:9051, 1:18102, 1:6400 respectively after the final immunization and demonstrated good neutralization responses to the six gene peptide containing 1a, 1b, 2a, 3a, 4a and 6a. The aluminum adjuvant increased the population of both specific ASCs (P < 0.01) and total ASCs(P < 0.05), with a proportional rise in concentrations of CD19+CD27+ (P < 0.05), as well as levels of IL-6, IL-10 (P < 0.05) in splenic lymphocytes. The results clearly indicated a significantly higher number of CD19+CD38+ splenic lymphocytes with the aluminum and pUCpGs10 adjuvant present compared to the control group(P < 0.05). Anti-HVR1 antibody in induced mice can cross-reactively capture HCV particles (10/12).Conclusions1. The aluminum adjuvant induces a potent Th2-biased immune response by increasing both the populations of specific and total ASCs and the ratio of CD19+CD27+ cells. 2. The pUCpGs10 complexed with the aluminum adjuvant boosts the population of plasma cells and increase the efficiency of the immune response. 3. The two adjuvants have synergistic effects on humoral immunity. 4. The recombinant HVR1 protein has the possibility of generating broadly reactive anti-HVR1 antibody.
Highlights
At present, more than 200 million people worldwide are infected with HCV [1], and are at risk of developing liver cirrhosis and hepatocellular carcinoma
The pUCpGs10 complexed with the aluminum adjuvant boosts the population of plasma cells and increase the efficiency of the immune response
We found that the HCV polyprotein alone induces very low antigen-specific serum antibodies
Summary
More than 200 million people worldwide are infected with HCV [1], and are at risk of developing liver cirrhosis and hepatocellular carcinoma. HCV has been shown to impair the humoral immunity response in several ways [2,3]. Viruses escape from immune responses through mutation in antibody and T cell epitopes has been shown for both HCV-infected humans and chimpanzees. An effective vaccine enhances host humoral immune responses in an antigen-specific manner by producing a broader spectrum neutralization antibody. Various peptides containing the B and T cell epitopes have been synthesized, such as recombinant polyprotein HVR1 and E1(HVR1: VARAAFGLTSIFSPGAKQN, GTHVTGGK VAYTTQGFTSFFSRGPSQK, QTTVVGGSQSHTVRG LTSLFSPGASQN, TTHTVGGSVARQVSHLTGLFSPG PQQKGSASSSEGGSTTTTTGGVQGHTTRGLVRLF SLGSKQN; E1: YQVRNSSGLYHVTNDCPNSS, YEVRN VSGVYHVTNDCSNSS, VQVKNTSSSYMVTNDCSNDS, LEWRNTSGLYVLTNDCSNSS, VHYRNASGVYHVTN DCPNTS, LTYGNSSGLYHLTND CPNSS.) involving different genotypes and variations of the quasi-species which conclude 6 kinds of genotype and the response rate to the sera of the HCV infected patients is more than 90% [4,5]. There has been study about cellular mechanism of coupling CpG and aluminum to HBV instead of humoral mechanism to HCV [7]
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