Novel DNA vaccine based on hepatitis B virus core gene induces specific immune responses in Balb/c mice

Xing, Yiping; Huang, Zhibin; Wang, Shi-Xia; Jie, Cheng; Li, Jun; Chou, Te-hui W.; Lü, Shan

doi:10.3748/wjg.v11.i29.4583

Cited by 8 publications

(8 citation statements)

References 13 publications

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“…Average percent killing observed in the spleen was about 83% while the average in the liver was 76%, showing that vaccine-induced CTLs that migrate to and are retained in the liver are capable of killing HBV peptide pulsed target cells. The percent killing in the spleen was comparable to previous studies that reported HBcAg-specific CTL responses using in vitro cytotoxicity assays 14 . To our knowledge, this is the first study to show induction of HBcAg-specific CTL responses in the liver, by any method and specifically by systemic immunization.…”

Section: Resultssupporting

confidence: 87%

“…However, single function CD8 T cells are likely effector cells. Lu et al 14 , demonstrated that immunization with HBcAg DNA could induce antigen-specific cytotoxic activity in vitro. Our data using an in vivo killing assay extended their findings.…”

Section: Discussionmentioning

confidence: 99%

“…Previous data from several groups suggest that these CTLs play a crucial role in the clearance of HBV during acute infection. In addition, recent findings suggest that the induction of both cellular and humoral immunogenicity against HBV antigens are important for controlling chronic infection 14 . Studies from our laboratory and other independent groups have shown that plasmid DNA delivery by electroporation (EP) represents an important strategy for enhancing cell or antibody mediated immune responses 15–18 , which we examined in this study.…”

Section: Introductionmentioning

confidence: 99%

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Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver

et al. 2012

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The prevalence of hepatitis B virus (HBV) infection in Asia and sub-Sahara Africa is alarming. With quarter of a billion people chronically infected worldwide and at risk of developing liver cancer, the need for a prophylactic or therapeutic vaccination approach that can effectively induce protective responses against the different genotypes of HBV is more important than ever. Such a strategy will require both the induction of a strong antigen-specific immune response and the subsequent deployment of immune response towards the liver. Here, we assessed the ability of a synthetic DNA vaccine encoding a recombinant consensus plasmid from genotype A through E of the HBcAg, to drive immunity in the liver. Intramuscular vaccination induced both strong antigen-specific T cell and high titer antibody responses systematically and in the liver. Furthermore, immunized mice showed strong cytotoxic responses that eliminate adoptively transferred HBV-coated target cells. Importantly, vaccine-induced immune responses provided protection from HBcAg plasmid-base liver transfection in a hydrodynamic liver transfection model. These data provide important insight into the generation of peripheral immune responses that are recruited to the liver- an approach that can be beneficial in the search for vaccines or immune-therapies to liver disease.

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Section: Resultssupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver

et al. 2012

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“…Studies have suggested that T cells play an important role in generating a functional immune response in the presence of the viral capsid for hepatitis B and C viruses (67,68). Similarly, for dengue virus 4 (DENV-4), epitopes in the capsid were shown to be recognized by cytotoxic T lymphocytes (CTLs) that were cross-reactive with other dengue virus serotypes (33).…”

Section: Discussionmentioning

confidence: 99%

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Garg

Sedano

Plata

et al. 2017

J Virol

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Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raise serious concerns regarding preparedness to combat this emerging virus. We used a virus-like particle (VLP)-based approach to develop a vaccine and a microneutralization assay for ZIKV. A synthetic capsid-premembrane-envelope (CprM-E) gene construct of ZIKV was used to generate reporter virus particles (RVPs) that package a green fluorescent protein (GFP) reporter-expressing West Nile virus (WNV) replicon. The assay was adapted to a 96-well format, similar to the plaque reduction neutralization test (PRNT), and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While the ZIKV prM-E construct alone was sufficient for generating VLPs, efficient VLP production from the C-prM-E construct could be achieved in the presence of the WNV NS2B-3 protease, which cleaves C from prM, allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than those with the DNA vaccines, with C-prM-E VLPs giving slightly higher titers than those with prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective, and economical VLP-based vaccine against ZIKV.IMPORTANCE To address the growing Zika virus epidemic, we undertook this study with two objectives: first, to develop a safe, effective, and economical vaccine for ZIKV, and second, to develop a rapid and versatile assay to detect the anti-ZIKV immune response. We generated a cell line stably expressing ZIKV prM-E that produces large amounts of VLPs in the supernatant and a ZIKV C-prM-E cell line that produces reporter virus particles upon transfection with a GFP replicon plasmid. The prM-E VLPs induced a strong neutralizing antibody response in mice that was better when the capsid was included. VLP-based vaccines showed significantly better neutralizing antibody responses than those with their DNA counterparts. The RVP-based microneutralization assay worked similarly to the PRNT assay, with a rapid GFP readout in a 96-well format. Our VLP-based platform provides a source for a ZIKV vaccine and diagnosis that can rapidly be adapted to current outbreaks.KEYWORDS C-prM-E, diagnostics, microneutralization, neutralization, PRNT, reporter, reporter virus particles, vaccine, Zika, prM-E S ince the identification of Zika virus (ZIKV) from a rhesus monkey in Uganda in 1947 (1, 2) until 2010, the virus predominantly circulated between Aedes mosquitoes and nonhuman primates. Periodic episodes were inde...

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“…16 HBc particles can present on their spherical surface any peptide inserted between A80-S81, which are located within the major immunodominant region. 20 The injection system used for delivery is also important in vaccine efficacy. Because the chosen method and route of administration could play key roles in the magnitude and quality of the resultant immune response, DNA vaccines require an appropriate delivery technology.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Reduction of High Blood Pressure by Angiotensin II DNA Vaccine in Spontaneously Hypertensive Rats

Kuroda

Nakagami

et al. 2015

Hypertension

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This study focuses on establishing an effective vaccine to treat hypertension.Research has targeted the components of the renin-angiotensin system (RAS), such as renin, Ang I, Ang II, and Ang II type 1 receptor (AT1R), for the treatment of hypertension. Unexpectedly, the initial studies encountered the difficulties in hypertension vaccines against these targets: renin vaccine caused autoimmune side effects, 2 whereas Ang I vaccine did not affect BP in a clinical trial.3 Vaccination against Ang II and AT1R successfully reduced BP, 4,5 but some problems remained that inhibited their translation to clinical use, such as insufficient reduction in BP to warrant clinical usage. 6 Recently, clinical trials of DNA vaccines in humans have been widely conducted. These trials demonstrated DNA vaccines are able to increase antibody titers and mediate therapeutic effects in several diseases. 7,8 In phase I clinical trial, neutralizing antibody responses to West Nile virus were elicited by DNA vaccination. 7 A therapeutic cytomegalovirus DNA vaccine significantly reduced the occurrence and recurrence of cytomegalovirus viremia and improved the time-toevent for viremia episodes when compared with placebo in Abstract-Recent research on vaccination has extended its scope from infectious diseases to chronic diseases, including Alzheimer disease, dyslipidemia, and hypertension. The aim of this study was to design DNA vaccines for high blood pressure and eventually develop human vaccine therapy to treat hypertension. Plasmid vector encoding hepatitis B coreangiotensin II (Ang II) fusion protein was injected into spontaneously hypertensive rats using needleless injection system. Anti-Ang II antibody was successfully produced in hepatitis B core-Ang II group, and antibody response against Ang II was sustained for at least 6 months. Systolic blood pressure was consistently lower in hepatitis B core-Ang II group after immunization, whereas blood pressure reduction was continued for at least 6 months. Perivascular fibrosis in heart tissue was also significantly decreased in hepatitis B core-Ang II group. Survival rate was significantly improved in hepatitis B core-Ang II group. This study demonstrated that Ang II DNA vaccine to spontaneously hypertensive rats significantly lowered high blood pressure for at least 6 months. In addition, Ang II DNA vaccines induced an adequate humoral immune response while avoiding the activation of self-reactive T cells, assessed by ELISPOT assay. MethodsMethods are available in the online-only Data Supplement. Results Construction of DNA VectorsWe selected Ang II as a target antigen to reduce BP in spontaneously hypertensive rats (SHRs), expecting that immunization against Ang II would minimize the inflammatory action of immune complexes because of the extremely low concentration of circulating Ang II. In addition, as Ang II receptor blockers are known to cause few severe adverse effects in clinical practice, we hypothesized that targeting a peptide in this pathway would have the similar safety profile...

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Novel DNA vaccine based on hepatitis B virus core gene induces specific immune responses in Balb/c mice

Abstract: pSW3891/HBc vaccination elicits specific anti-HBc response and induces HBc-specific CTL response in immunized Balb/c mice.

Cited by 8 publications

References 13 publications

Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver

Synthetic DNA immunogen encoding hepatitis B core antigen drives immune response in liver

Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus

Long-Term Reduction of High Blood Pressure by Angiotensin II DNA Vaccine in Spontaneously Hypertensive Rats

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