Enhanced specific immune responses by CpG DNA in mice immunized with recombinant hepatitis B surface antigen and HB vaccine

Zhang, Xiancheng; He, Peng; Hu, Zhongliang; Wang, Xingtai; Liang, Zhenglun

doi:10.1186/1743-422x-8-78

Cited by 7 publications

(4 citation statements)

References 24 publications

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“…In contrast, CpG ODN induces a strong Th1 response with predominantly IgG2a Abs and CTLs, even when mixed with alum. Indeed, mice immunised with 20 µg CpG DNA and regular vaccine (containing alum adjuvant) had the highest concentration of antibody, IL-10 and IL-12 production, and activation of CD80 and CD86 molecules [26]. The Ab response was significantly improved in macaques and human clinical trials upon co-administration of CpG with Engerix B (the human hepatitis B vaccine), further confirming the adjuvant activity of CpG [27]–[32].…”

Section: Discussionmentioning

confidence: 74%

Poly(I:C)/Alum Mixed Adjuvant Priming Enhances HBV Subunit Vaccine-Induced Immunity in Mice When Combined with Recombinant Adenoviral-Based HBV Vaccine Boosting

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 74%

Poly(I:C)/Alum Mixed Adjuvant Priming Enhances HBV Subunit Vaccine-Induced Immunity in Mice When Combined with Recombinant Adenoviral-Based HBV Vaccine Boosting

et al. 2013

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“…The hepatitis B vaccine adjuvant alum is generally used for vaccination, although 10% of the population has low or no antibody response. Efforts to find more efficient vaccine adjuvants for better antibody response as well as antiviral immunity are continuing 40 . The present study compared the production of monoclonal antibody against HBsAg using three different formulations of adjuvants including alum either alone or in combination with CFA or CpG ODN.…”

Section: Discussionmentioning

confidence: 99%

“…It seemed that a strong synergetic response was observed when the CpG ODN was used together with alum. It is assumed that this effect of CpG ODN and alum is mediated via proliferation induction of almost all B cells and triggered polyclonal immunoglobulin secretion, which is T cell independent and antigen nonspecific 38 , as well as improved function of professional APCs by stimulation of TLR9 expressed on these cells 40 . Antibody detection in supernatants of hybridomas derived from mice immunized with three different formulations of adjuvants revealed similar results as obtained by serum samples; in other words, nonsignificant higher antibody titers were observed in supernatants of (HBsAg+Alum)+CpG, (HBsAg+Alum)+FA, and (HBsAg+Alum), respectively ( Figure 4 ).…”

Section: Discussionmentioning

confidence: 99%

CpG-Containing Oligodeoxynucleotides and Freund Adjuvant in Combination with Alum Augment the Production of Monoclonal Antibodies Against Recombinant HBsAg

Kohnehshahr¹,

Delirezh²,

Maleki³

2022

AJMB

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Background: Adjuvants are essential to potentiate the immune response to inoculated antigens and play a central role in vaccine development. Alum is generally used as a classic adjuvant, although it does not stimulate proper immunity, and some of the immunized subjects have low or no antibody response. Efforts have been continued to find more efficient adjuvants for better antibody responses. In the present study, the efficacy of three formulations of adjuvants, i.e. Cysteine p Guanine Oligodeoxynucleotide (CpG ODN), alum, and Freund, in the production of monoclonal anti Hepatitis B Surface Antigen (HBsAg) antibodies was investigated. Methods: To immunize mice, regular hepatitis B vaccine containing recombinant HBsAg and alum was used with CpG ODN or Freund adjuvants, and splenocytes of hyperimmunized mice were fused with murine myeloma Sp2/0 cells. Positive hybridomas were selected by Enzyme-Linked Immunosorbent Assay (ELISA) using HBsAg as coating antigen followed by a limited dilution process. Results: The results showed that by using all three formulations of adjuvants, monoclonal antibody (mAb) specific to HBsAg was successfully generated. It was also found that the mice immunized with (HBsAg + Alum) + CpG had the highest concentration of antibody production in serum and hybridoma supernatants as well as positive clones. Based on these findings, the addition of CpG ODN also induced a higher antibody response compared with Complete Freund’s Adjuvant (CFA). Conclusion: Results of this study showed that CpG and Freund adjuvants could be efficient partners for alum in the immunization period of the process of monoclonal antibody production.

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“…CpG1, CpG2, CpG3, CpG4, and CpG5 are B-type CpG ODNs with different sequences. These CpG ODNs are designed based on BW006, which has previously been shown to have stimulatory activity ( 34 ). For in vitro screening of CpG ODNs, BW006 and a meaningless sequence of GC were used as positive and negative controls, respectively.…”

Section: Methodsmentioning

confidence: 99%

A novel CpG ODN compound adjuvant enhances immune response to spike subunit vaccines of porcine epidemic diarrhea virus

Wang,

Liu,

et al. 2024

Front. Immunol.

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CpG oligodeoxynucleotides (CpG ODNs) boost the humoral and cellular immune responses to antigens through interaction with Toll-like receptor 9 (TLR9). These CpG ODNs have been extensively utilized in human vaccines. In our study, we evaluated five B-type CpG ODNs that have stimulatory effects on pigs by measuring the proliferation of porcine peripheral blood mononuclear cells (PBMCs) and assessing interferon gamma (IFN-γ) secretion. Furthermore, this study examined the immunoenhancing effects of the MF59 and CpG ODNs compound adjuvant in mouse and piglet models of porcine epidemic diarrhea virus (PEDV) subunit vaccine administration. The in vitro screening revealed that the CpG ODN named CpG5 significantly stimulated the proliferation of porcine PBMCs and elevated IFN-γ secretion levels. In the mouse vaccination model, CpG5 compound adjuvant significantly bolstered the humoral and cellular immune responses to the PEDV subunit vaccines, leading to Th1 immune responses characterized by increased IFN-γ and IgG2a levels. In piglets, the neutralizing antibody titer was significantly enhanced with CpG5 compound adjuvant, alongside a considerable increase in CD8+ T lymphocytes proportion. The combination of MF59 adjuvant and CpG5 exhibits a synergistic effect, resulting in an earlier, more intense, and long-lasting immune response in subunit vaccines for PEDV. This combination holds significant promise as a robust candidate for the development of vaccine adjuvant.

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Enhanced specific immune responses by CpG DNA in mice immunized with recombinant hepatitis B surface antigen and HB vaccine

Cited by 7 publications

References 24 publications

Poly(I:C)/Alum Mixed Adjuvant Priming Enhances HBV Subunit Vaccine-Induced Immunity in Mice When Combined with Recombinant Adenoviral-Based HBV Vaccine Boosting

Poly(I:C)/Alum Mixed Adjuvant Priming Enhances HBV Subunit Vaccine-Induced Immunity in Mice When Combined with Recombinant Adenoviral-Based HBV Vaccine Boosting

CpG-Containing Oligodeoxynucleotides and Freund Adjuvant in Combination with Alum Augment the Production of Monoclonal Antibodies Against Recombinant HBsAg

A novel CpG ODN compound adjuvant enhances immune response to spike subunit vaccines of porcine epidemic diarrhea virus

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