Three new anti-HBV active constituents from the traditional Chinese herb of Yin-Chen (Artemisia scoparia).

Posted by on 23 Sep 2016 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Three new anti-HBV active constituents from the traditional Chinese herb of Yin-Chen (Artemisia scoparia). J Ethnopharmacol. 2015 Dec 24;176:109-17 Authors: Geng CA, Huang XY, Chen XL, Ma YB, Rong GQ, Zhao Y, Zhang XM, Chen JJ Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Yin-Chen is a famous traditional Chinese medicine (TCM) in China for the treatment of acute and chronic hepatitis. Two species, namely Artemisia scoparia and Artemisia capillaris, are documented in Chinese Pharmacopoeia as the authentic resources for Yin-Chen. Previous investigation has proved that chlorogenic acid analogs and phenolic acids are two main types of the anti-HBV active constituents of A. capillaris. However, there is no investigation concerned with the anti-HBV components of A. scoparia. AIM OF THE STUDY: The aim of the present study is to recognize the new anti-HBV constituents of A. scoparia by detailed LCMS analyses. MATERIALS AND METHODS: LCMS and bioassay-guided fractionation on the active part of A. scoparia led to the isolation of three new compounds. Their structures were determined by detailed spectroscopic analyses. Anti-HBV assay involving inhibition on HBsAg and HBeAg secretions and HBV DNA replication were performed in virto on HepG 2.2.15 cell line. RESULTS: The 90% ethanol extract of A. scoparia was revealed with anti-HBV activity for the first time, which was further separated into several fractions by column chromatography. Fr. D-4 was revealed with the highest anti-HBV activity, from which three new compounds including one unusual 4-pyridone glucoside (1) and two polyacetylene glucosides (2-3) were isolated under the guidance of LCMS analyses. Compounds 1-3 exhibited activity against the secretions of HBsAg and HBeAg, and HBV DNA replication. In particular, compounds 2 and 3 inhibited HBV DNA replication with IC50 values of 0.07 ± 0.04 and 0.012 ± 0.05 mM, with SI values of 23.6 and 17.1, respectively. Based on the MS/MS experiment, the fragmentation pathways of 1 in both positive and negative modes, and 2 and 3 in negative mode were proposed. The ion pairs of 388-208 (positive) and 432-206 (negative) for 1, 503-341 (negative) for 2, and 503-203 (negative) for 3, could be recognized as their respective diagnostic ions. CONCLUSIONS: The first time investigation on the anti-HBV constituents of A. scoparia yielded three new active compounds, which will provide valuable information for understanding the ethnopharmacological usage of Yin-Chen, as well as the chemical difference with A. capillaris. PMID: 26505294 [PubMed – indexed for MEDLINE]

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Three new anti-HBV active constituents from the traditional Chinese herb of Yin-Chen (Artemisia scoparia).

[TLR9 expression is positively correlated with the levels of CD38, HLA-DR and CD95 on peripheral blood mononuclear cells in chronic HBV infected…

Posted by on 23 Sep 2016 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [TLR9 expression is positively correlated with the levels of CD38, HLA-DR and CD95 on peripheral blood mononuclear cells in chronic HBV infected patients]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016 May;32(5):660-5 Authors: Mao X, Peng L, Liu X, Yang Y, Wang Q, Wang D, Xiao J, Leng J Abstract OBJECTIVE: To explore the relationship between the expression of TLR9 and the levels of CD38, HLA-DR and CD95 on peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B virus (HBV) infected patients. METHODS: 70 chronic HBV infected patients and 12 healthy donors were enrolled in this study, and density gradient centrifugation was used to isolate PBMCs from peripheral blood with EDTA for anticoagulation. Flow cytometry was used to detect the levels of TLR9, CD38, HLA-DR and CD95 on PBMCs. RESULTS: Compared to the healthy donors, chronic HBV infected patients with low viral load or high viral load had significantly higher levels of TLR9, HLA-DR and CD95 on PMBCs. Furthermore, the co-expression rates of TLR9 and CD38, HLA-DR, CD95 on PBMCs were obviously higher than those of the healthy donors. Correlation analysis showed that the expression of TLR9 was positively correlated with CD38 (r=0.345), HLA-DR (r=0.334), CD95 (r=0.227) on PBMCs in the patients with chronic HBV infection. CONCLUSION: The expression of TLR9 increased and was positively associated with CD38, HLA-DR and CD95 on PBMCs during chronic HBV infection. PMID: 27126946 [PubMed – indexed for MEDLINE]

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[TLR9 expression is positively correlated with the levels of CD38, HLA-DR and CD95 on peripheral blood mononuclear cells in chronic HBV infected…

Therapeutic Potential of Cell Penetrating Peptides (CPPs) and Cationic Polymers for Chronic Hepatitis B.

Posted by on 15 Sep 2016 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Therapeutic Potential of Cell Penetrating Peptides (CPPs) and Cationic Polymers for Chronic Hepatitis B. Int J Mol Sci. 2015;16(12):28230-41 Authors: Ndeboko B, Lemamy GJ, Nielsen PE, Cova L Abstract Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. Because current anti-HBV treatments are only virostatic, there is an urgent need for development of alternative antiviral approaches. In this context, cell-penetrating peptides (CPPs) and cationic polymers, such as chitosan (CS), appear of particular interest as nonviral vectors due to their capacity to facilitate cellular delivery of bioactive cargoes including peptide nucleic acids (PNAs) or DNA vaccines. We have investigated the ability of a PNA conjugated to different CPPs to inhibit the replication of duck hepatitis B virus (DHBV), a reference model for human HBV infection. The in vivo administration of PNA-CPP conjugates to neonatal ducklings showed that they reached the liver and inhibited DHBV replication. Interestingly, our results indicated also that a modified CPP (CatLip) alone, in the absence of its PNA cargo, was able to drastically inhibit late stages of DHBV replication. In the mouse model, conjugation of HBV DNA vaccine to modified CS (Man-CS-Phe) improved cellular and humoral responses to plasmid-encoded antigen. Moreover, other systems for gene delivery were investigated including CPP-modified CS and cationic nanoparticles. The results showed that these nonviral vectors considerably increased plasmid DNA uptake and expression. Collectively promising results obtained in preclinical studies suggest the usefulness of these safe delivery systems for the development of novel therapeutics against chronic hepatitis B. PMID: 26633356 [PubMed – indexed for MEDLINE]

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Therapeutic Potential of Cell Penetrating Peptides (CPPs) and Cationic Polymers for Chronic Hepatitis B.

Cost-effectiveness of Lamivudine, Telbivudine, Adefovir Dipivoxil and Entecavir on decompensated hepatitis B virus-related cirrhosis.

Posted by on 30 Mar 2016 | Tagged as: Hepatitis B Alternative Medicine

Cost-effectiveness of Lamivudine, Telbivudine, Adefovir Dipivoxil and Entecavir on decompensated hepatitis B virus-related cirrhosis. Eur Rev Med Pharmacol Sci. 2016 Mar;20(5):866-872 Authors: Wang GL, Liu Y, Qiu P, Zhou SF, Xu LF, Wen P, Wen JB, Xiao XZ Abstract OBJECTIVE: To evaluate the cost-effectiveness of lamivudine (LMV), telbivudine (LdT), adefovir dipivoxil (ADV) and entecavir (ETV) on decompensated hepatitis B virus-related cirrhosis. PATIENTS AND METHODS: 1332 patients with decompensated hepatitis B virus-related cirrhosis were randomly assigned into 5 groups with different clinical treatment including LMV treatment, LdT treatment, ADV treatment, LMV+ADV treatment and ETV treatment. And then the liver function, Child-Pugh scores, sero-conversion of HBeAg/HBeAb, polymerase gene mutations, cost-effectiveness, incremental cost-effectiveness and side effects were investigated and further analyzed. RESULTS: LMV, ADV, LdT, LMV+ADV and ETV were all effective on decreasing Child-Pugh scores and conversing negatively hepatitis B virus (HBV) DNA and HBeAg, whereas LMV+ADV and ETV more effective than LMV, ADV and LdT. HBV DNA polymerase genotypic mutations were rare in the 5 groups. The less mutation rate was found in the LMV+ADV and ETV group than in the LMV, ADV and LdT group. Compared to the cost-effectiveness and incremental cost-effectiveness ratio, ETV was the optimal selection, LMV+ADV was the alternative selection and LMV was the cheapest option. The side effects of the 5 plans were all rare and could be controlled. CONCLUSIONS: LMV, ADV, LdT, LMV+ADV and ETV were all effective on treatment of decompensated hepatitis B virus-related cirrhosis whereas ETV and LMV+ADV were recommended. PMID: 27010143 [PubMed – as supplied by publisher]

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Cost-effectiveness of Lamivudine, Telbivudine, Adefovir Dipivoxil and Entecavir on decompensated hepatitis B virus-related cirrhosis.

Inhibitory effect of Phyllanthus urinaria L. extract on the replication of lamivudine-resistant hepatitis B virus in vitro.

Posted by on 04 Aug 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Inhibitory effect of Phyllanthus urinaria L. extract on the replication of lamivudine-resistant hepatitis B virus in vitro. BMC Complement Altern Med. 2015;15:255 Authors: Jung J, Kim NK, Park S, Shin HJ, Hwang SG, Kim K Abstract BACKGROUND: Long-term treatment of chronic hepatitis B (CHB) with nucleos(t)ide analogs results in the emergence of drug-resistant hepatitis B virus (HBV) harboring mutations in the polymerase (P) gene. The Phyllanthus extract has anti-HBV activity; however, its antiviral activity against lamivudine (LMV)-resistant mutants has not been examined. METHODS: HBV harboring LMV-resistant mutations (rtM204I, rtM204V, and rtM204S) in the P gene at the YMDD ((203)tyrosine-methionine-aspartate-aspartate(206)) reverse transcriptase (RT) active site were generated and their sensitivity to Phyllanthus urinaria koreanis extract examined. Southern blotting and real-time PCR were used to determine the concentration of plant extract required to inhibit HBV DNA synthesis by 50 and 90 % (EC50 and EC90, respectively). An enzyme-linked immunosorbent assay was used to measure the EC50 of HBV surface antigen (HBsAg) and HBV core antigen (HBcAg) secretion, and the 50 % cytotoxic concentration of the extract was measured in a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Real-time RT-PCR was used to measure mRNA expression levels. RESULTS: The expression of intracellular HBV DNAs in HBV WT- or mutant-transfected HepG2 cells decreased upon treatment with Phyllanthus extract. The secretion of HBsAg and HBcAg also fell in a dose-dependent manner. Phyllanthus extract induced interferon-beta (IFN-β), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) mRNA expression in HBV WT-transfected HepG2 cells, possibly via activation of extracellular signal-regulated kinases and c-jun N-terminal kinases and the induction of retinoic acid inducible gene-I, toll-like receptor 3, myeloid differentiation primary response gene 88, and/or tumor necrosis factor receptor-associated factor 6 gene expression. HBV transfection in the absence of extract or exposure of cells to extract alone did not trigger these signaling cascades. CONCLUSIONS: Phyllanthus extract inhibited HBV DNA synthesis and HBsAg and HBcAg secretion by replicating cells harboring HBV wild-type and LMV-resistant mutants, likely by inducing the expression of IFN-β, COX-2, and IL-6. These data indicate that Phyllanthus extract may be useful as an alternative therapeutic agent for the treatment of drug-resistant CHB patients. PMID: 26220282 [PubMed – in process]

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Inhibitory effect of Phyllanthus urinaria L. extract on the replication of lamivudine-resistant hepatitis B virus in vitro.

Public health response to a large-scale endoscopy infection control lapse in a nonhospital clinic.

Posted by on 28 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Public health response to a large-scale endoscopy infection control lapse in a nonhospital clinic. Can J Infect Dis Med Microbiol. 2015 Mar-Apr;26(2):77-84 Authors: Willmore J, Ellis E, Etches V, Labrecque L, Osiowy C, Andonov A, McDermaid C, Majury A, Achonu C, Maher M, MacLean B, Levy I Abstract OBJECTIVE: To determine whether transmission of blood-borne pathogens (BBPs) (hepatitis B virus [HBV], hepatitis C virus [HCV] and HIV) occurred as a result of endoscopy reprocessing failures identified during an inspection of a nonhospital endoscopy clinic in 2011. METHODS: The present analysis was a retrospective cohort study. Registered notification letters were mailed to 6992 patients who underwent endoscopy from 2002 to 2011 at one Canadian nonhospital endoscopy clinic, informing them of the infection control lapse and offering BBP testing. Multimedia communications and a telephone line supplemented notification. A retrospective study of patients with BBPs was performed with viral genetic testing and risk factor assessment for eligible patients. Risk for infection among patients whose procedure was within seven days of a known positive patient was compared with those whose procedure was performed more than seven days after a known postive patient. The seven-day period was selected as the period most likely to present a risk for transmission based on the documented cleaning procedures at the clinic and the available literature on virus survival. RESULTS: Ninety-five percent (6628 of 6992) of patients/estates were contacted and 5042 of 6728 (75%) living patients completed BBP testing. Three were newly diagnosed with HBV and 14 with HCV. Twenty-three and 48 tested positive for previously known HBV or HCV, respectively, 367 were immune to HBV due to natural infection and one was immune to HBV due to immunization. None tested positive for HIV. Sequencing did not reveal any relationships among the 46 unique case patients with viral genetic test results available. Ninety-three percent of patients reported alternative risk factors for BBP. An increased risk for infection among those who underwent a procedure within seven days of a known HBV or HCV case was not demonstrated. CONCLUSIONS: Endoscopy reprocessing failures were not associated with an increased risk for BBP among individuals tested. PMID: 26015789 [PubMed]

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Public health response to a large-scale endoscopy infection control lapse in a nonhospital clinic.

[Correlation study on Chinese medical syndrome types of chronic hepatitis B patients and HLA-DR13 gene, BCP mutation, and T-lymphocyte subsets].

Posted by on 20 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Correlation study on Chinese medical syndrome types of chronic hepatitis B patients and HLA-DR13 gene, BCP mutation, and T-lymphocyte subsets]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Nov;34(11):1315-8 Authors: Yang XR, Liu Y, Ouyang J, Wang XK, Diao WX Abstract OBJECTIVE: To explore the correlation between the HLA-DR13, basic core promoter (BCP), changes of T lymphocyte subset and clinical Chinese medical syndromes of chronic hepatitis B (CHB). METHODS: Totally 102 CHB patients were syndrome typed as Gan depression Pi deficiency syndrome (GDPDS), Pi-Shen yang deficiency syndrome (PSYDS), Gan-gallbladder dampness heat syndrome (GGDHS), Gan-Shen yin deficiency syndrome (GSYDS), and static blood blocking collaterals syndrome (SBBCS). Besides, 30 healthy subjects were recruited as the normal control group. The blood HBV-DNA level and HLA-DR13 gene were detected with real time fluorescent PCR. The expression of CD4+ and CD8+ in T lymphocytes was detected using flow cytometry. The mutation of serum A1762T/G1764A was detected using PCR sequencing. Hepatitis Be antigen (HBeAg) was detected with ELISA, and correlation between various Chinese medical syndrome types and objective indicators were analyzed. RESULTS: There was no statistical difference in HBV-DNA quantitative results among various syndrome types (P > 0.05). HBeAg positive rate was higher in GDPDS than in other syndrome types (P < 0.05). It was sequenced as GDPDS > GSYDS > SBBCS > GGDHS > PSYDS. Compared with the normal control group, percentages of CD3+ and CD3+ CD4+ were lower in PSYDS (P < 0.05). The ratio of CD3+ CD4+/CD3+ CD8 was lower in GGDHS and PSYDS than in the normal control group (P < 0.05). There was no statistical difference in the CD3+ CD8+ percentage among various syndrome types (P > 0.05). The quantitation of HLA-DR13 gene was lower in GDPDS and GSYDS than in the normal control group (P < 0.05). The positive rate of BCP mutation was higher in GSYDS than in other syndrome types (P < 0.05). CONCLUSION: Co-detection results of HLA-DR13 and BCP could be used as reference indices of Chinese medical syndrome typing of CHB. PMID: 25566621 [PubMed – indexed for MEDLINE]

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[Correlation study on Chinese medical syndrome types of chronic hepatitis B patients and HLA-DR13 gene, BCP mutation, and T-lymphocyte subsets].

[Differential expression of microRNA in chronic hepatitis B patients of pi-wei dampness-heat syndrome and of gan depression Pi deficiency syndrome: a…

Posted by on 20 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Differential expression of microRNA in chronic hepatitis B patients of pi-wei dampness-heat syndrome and of gan depression Pi deficiency syndrome: a primary research]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Nov;34(11):1324-8 Authors: Wang EC, Zhang L, Liu HW, Guo YL, Zhang F, He CW, Shen MM, Feng QS Abstract OBJECTIVE: To explore different microRNA expression profiles between chronic hepatitis B (CHB) patients of Pi-Wei dampness-heat syndrome (PWDHS) and Gan depression Pi deficiency syndrome (GDPDS). METHODS: By applying gene chip technology, blood samples from CHB patients of PWDHS (3 cases), GDPDS (3 cases), and healthy volunteers (3 cases) were withdrawn and microRNA detected. The microRNA was screened and functional analyses performed by using SAS system. RESULTS: Totally 77 microRNAs with differential expression were screened from CHB patients of PWDHS and healthy volunteers, including 60 up-regulated microRNAs and 17 down-regulated microRNAs. Functions of target genes were mainly associated with transcription factors, gas exchange, adverse stimulating, regulation of enzyme activities, developing of the immune system, and the process of actin filaments. Totally 41 microRNAs with differential expression were screened from CHB patients of GDPDS and healthy volunteers, including 32 up-regulated microRNAs and 9 down-regulated microRNAs. Functions of target genes were mainly associated with binding to nucleotide or chromatin, inhibition and activation of transcription, biosynthesis, regulation of metabolic process, regulation of enzyme activities, developing of the immune system, the process of actin filaments, and IL-12. Totally 6 microRNAs with differential expression were screened from CHB patients of PWDHS and CHB patients of GDPDS, including 1 up-regulated microRNA and 5 down-regulated microRNAs. Functions of target genes were mainly associated with transmembrane transport, regulation of transcription factors, metabolism of hormones, developing of the immune system, the process of actin filaments, regulation of metabolic process, response to exterior stimulation, and so on. CONCLUSION: There existed differentially expressed microRNAs (spectrum) between CHB patients of PWDHS and CHB patients of GDPDS. PMID: 25566623 [PubMed – indexed for MEDLINE]

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[Differential expression of microRNA in chronic hepatitis B patients of pi-wei dampness-heat syndrome and of gan depression Pi deficiency syndrome: a…

Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients.

Posted by on 15 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients. J Transl Med. 2015 May 13;13(1):157 Authors: Dammermann W, Bentzien F, Stiel EM, Kühne C, Ullrich S, Zur Wiesch JS, Lüth S Abstract BACKGROUND: Interferon gamma release assays (IGRA) have been developed to support easy and fast diagnosis of diseases like tuberculosis, and CMV in transplant patients. IGRAs focus on cellular immunity especially memory T cells and thus also allow rapid screening prior to complex flow cytometric testing. Here, we describe a novel, sensitive whole blood based cytokine release assay capable of assessing T cell responsiveness to HBV antigens in Hepatitis B patients and assessing hepatitis B vaccination status in healthy individuals. METHODS: Seventy two chronic Hepatitis B patients (CHB), 8 acute hepatitis B patients (AHB) and 80 healthy controls (HC) were tested by ELISA for IFNγ- and IL2-secretion in whole blood after challenge with synthetic peptide libraries of hepatitis B core antigen (HBcAg) or hepatitis B surface antigen (HBsAg). RESULTS: The developed IGRA test reliably differentiated between Hepatitis B patients, vaccinees and unvaccinated healthy controls. Treatment naïve and treated CHB patients showed a weaker IFNγ response to HBcAg (16 ± 5 and 35 ± 28 pg/ml, respectively) compared to the AHB group (82 ± 39 pg/ml), whereas HC remained unresponsive (6 ± 1 pg/ml). IL2 levels after HBcAg challenge were also higher in the AHB group compared to naive and treated CHB as well as HC (47 ± 21 vs. 12 ± 3, 15 ± 10 and 12 ± 9 pg/ml, respectively). HBsAg stimulation led to increased IFNγ and IL2 levels in the AHB group (33 ± 12 and 22 ± 12 pg/ml) and even higher levels in HC due to a high hepatitis B vaccination rate (41 ± 10 and 167 ± 58 pg/ml). Naive and treated CHB patients developed no or only weaker IFNγ or IL2 responses to HBsAg (5 ± 2 and 12 ± 7 pg/ml, for naive CHB, 12 ± 10 and 18 ± 15 pg/ml, for treated CHB). For HC, IL2 release after HBsAg stimulation depicted hepatitis B vaccination status with a diagnostic sensitivity and specificity of 85 % and 90 %. CONCLUSION: Our novel whole blood based cytokine release assay constitutes an easy and robust tool for screening HBV specific cellular immunity as alternative to flow cytometry or ELISPOT assays. PMID: 25968473 [PubMed – as supplied by publisher]

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Development of a novel IGRA assay to test T cell responsiveness to HBV antigens in whole blood of chronic Hepatitis B patients.

Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses.

Posted by on 07 May 2015 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses. Vaccine. 2015 May 2; Authors: Hayden CA, Fischer ME, Andrews BL, Chilton HC, Turner DD, Walker JH, Tizard IR, Howard JA Abstract BACKGROUND: The hepatitis B surface antigen (HBsAg) has been administered over the last 20 years as a parenteral vaccine against the hepatitis B virus (HBV). Despite high seroconversion rates, chronic infection rates are still high worldwide. Orally delivered vaccines provide a practical alternative to injected vaccines, potentially helping poorly responding populations and providing a viable alternative for populations in remote locations. Anamnestic responses are vital to establishing the efficacy of a given vaccine and have been assessed in this study using a plant-based oral delivery platform expressing the hepatitis B surface antigen (HBsAg). METHODS: Long-term immunological memory was assessed in mice injected with a primary dose of Recombivax(®) and boosted with orally-delivered HBsAg wafers, control wafers, or parenterally-delivered commercial vaccine (Recombivax(®)). RESULTS: Mice boosted with HBsAg orally-administered wafers displayed sharp increases in mucosal IgA titers in fecal material and steep increases in serum IgA, whereas mice boosted with Recombivax(®) showed no detectable levels of IgA in either fecal or serum samples following four boosting treatments. Long-term memory in the orally-treated mice was evidenced by sustained fecal IgA, and serum IgA, IgG, and mIU/mL over one year, while Recombivax(®)-treated mice displayed sustained serum IgG and mIU/mL. Furthermore, sharp increases in these same antibodies were induced after re-boosting at 47 and 50 weeks post-primary injection. CONCLUSIONS: Orally-delivered vaccines can provide long-term immune responses mucosally and systemically. For sexually-transmitted diseases that can be acquired at mucosal surfaces, such as HBV, an oral delivery platform may provide added protection over a conventional parenterally administered vaccine. PMID: 25944300 [PubMed – as supplied by publisher]

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Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses.

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