Intranasal vaccination with HBs and HBc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-HBs IgA, and IFNG response

Sanada, Takahiro; Yamamoto, Naoki; Kayesh, Mohammad Enamul Hoque; Tsukiyama-Kohara, Kyoko; Hasegawa, Hideki; Miyazaki, Takashi; Takano, Junichiro; Shiogama, Yumiko; Yasutomi, Yasuhiro; Goh, Yasumasa; Yoshida, Osamu; Hiasa, Yoichi; Kohara, Michinori

doi:10.1016/j.bbrc.2019.09.072

Cited by 10 publications

(22 citation statements)

References 18 publications

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“…Since HBV patient serum contains large quantities of HBs-S antigen [5], we focused on this molecule as a possible mediator of this enhancement. We evaluated the effects of HBs-S and HBs-L in HBV attachment to NTCP-expressing HepG2 cells (HepG2-hNTCP-30 cells) [9]. The HBs-S or HBs-L protein was mixed with HBV, and the resulting mixture then was inoculated to the cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

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HBs-S antigen-dependent enhancement of HBV infection

Sanada

Yoshida

Hiasa

et al. 2022

Preprint

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Background & Aims: In natural infections with hepatitis B virus (HBV), large amounts of hepatitis B surface-small antigen (HBs-S) subviral particles (SVPs), which do not contain viral nucleocapsid, are secreted into the blood. The function of excess amounts of SVPs remains largely unknown. In this study, we analyzed the function of HBs-S in HBV infection. Methods: The effect of HBs-S in HBV infection was evaluated in a human hepatoma cell line, in primary human hepatocytes, and in chimeric mice with humanized livers. To analyze the involvement of glycosaminoglycan, HBs-S attachment to cells in the presence of heparin was evaluated by enzyme-linked immunosorbent assay (ELISA), and the enhancement of viral attachment was evaluated by measurement of viral DNA. Additionally, the interaction between HBs-S and viral particles was analyzed by immunoprecipitation. Results: Attachment of the HBV DNA to cells inoculated with the combination of virus and HBs-S was significantly higher than that to cells inoculated with HBV only. Pretreatment of the cells with HBs-S also increased viral DNA levels significantly compared to that in untreated cells. In contrast, HBs-L did not enhance the viral attachment. Enhancement of viral attachment was associated with the attachment of HBs-S to the cells via heparan sulfate. HBs-S also interacted with the viral particle. Furthermore, in chimeric mice with humanized livers, HBs-S enhanced HBV infection. Conclusions: We demonstrated that HBs-S enhances viral attachment in vitro and viral infection in vivo. HBs-S interacted with heparan sulfate on the cellular surface, and this interaction contributed to the enhancement of viral attachment. These data indicate that HBs-S enhances the viral infection, and may contribute to the high transmissibility of HBV.

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Section: Resultsmentioning

confidence: 99%

“…HepG2 and HepG2-hNTCP-30 cells were cultured on type I, collagen-coated, 48-well plates as described previously [9]. PXB-cells were cultured on type I, collagen-coated, 48-well plates using maintenance medium as previously described [10].…”

Section: Methodsmentioning

confidence: 99%

HBs-S antigen-dependent enhancement of HBV infection

Sanada

Yoshida

Hiasa

et al. 2022

Preprint

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“…A therapeutic vaccine candidate containing both HBsAg and core antigen (HBcAg), NASVAC reduced serum viral DNA levels more than Peg-IFN treatment in an open, phase III, randomized, treatment-controlled clinical trial [ 141 ]. Moreover, a recent study in a Tupaia model demonstrated that that intranasal immunization with HBs-S or HBs-L combined with HBc and formulated with carboxyl vinyl polymer (CVP) could induce strong IgG, IgA, neutralizing antibody, and HBV protein-specific IFN-γ immune responses [ 87 ].…”

Section: Adaptive Immune Response Modulationmentioning

confidence: 99%

Targeting Host Innate and Adaptive Immunity to Achieve the Functional Cure of Chronic Hepatitis B

et al. 2020

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Despite the availability of an effective preventive vaccine for hepatitis B virus (HBV) for over 38 years, chronic HBV (CHB) infection remains a global health burden with around 257 million patients. The ideal treatment goal for CHB infection would be to achieve complete cure; however, current therapies such as peg-interferon and nucleos(t)ide analogs are unable to achieve the functional cure, the newly set target for HBV chronic infection. Considering the fact functional cure has been accepted as an endpoint in the treatment of chronic hepatitis B by scientific committee, the development of alternative therapeutic strategies is urgently needed to functionally cure CHB infection. A promising target for future therapeutic strategies is immune modulation to restore dysfunctional HBV-specific immunity. In this review, we provide an overview of the progress in alternative therapeutic strategies, including immune-based therapeutic approaches that enhance host innate and adaptive immunity to achieve and increase the functional cure from CHB infection.

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“…Thus, future studies with animal models that support efficient HBV infection are necessary to further investigate the modification of TLRs by HBV infection. Establishment of an adaptive strain producing high viral loads in the Tupaia model may further contribute to the elucidation of pathogenesis and immune response for the development of antivirals [65] and prophylactics.…”

Section: Hepatitis B Virus (Hbv)mentioning

confidence: 99%

Pathogenesis and Immune Response Caused by Vector-Borne and Other Viral Infections in a Tupaia Model

et al. 2019

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The Tupaia or tree shrew (Tupaia belangeri), a small mammal of the Tupaiidae family, is an increasingly used and promising infection model for virological and immunological research. Recently, sequencing of the Tupaia whole genome revealed that it is more homologous to the genome of humans than of rodents. Viral infections are a global threat to human health, and a complex series of events are involved in the interactions between a virus and the host immune system, which play important roles in the activation of an immune response and the outcome of an infection. Majority of immune response data in viral infections are obtained from studies using animal models that enhance the understanding of host-virus interactions; a proper understanding of these interactions is very important for the development of effective antivirals and prophylactics. Therefore, animal models that are permissive to infection and that recapitulate human disease pathogenesis and immune responses to viral infections are essential. Several studies have shown the permissiveness of Tupaia to a number of important human viral infections in vitro and in vivo without prior adaptation of the viruses; the immune responses and clinical manifestations were comparable to those observed in human infections. Thus, the Tupaia is being utilized and developed as a promising immunocompetent small animal model for viral infection studies. In this review, we focused on the immune responses, mostly innate, during viral infection and pathogenesis in the Tupaia model; we evaluated the interaction between the virus and the components of host resistance, the usefulness of this model for immunopathogenesis studies, and the vaccines and antivirals available.

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Intranasal vaccination with HBs and HBc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-HBs IgA, and IFNG response

Cited by 10 publications

References 18 publications

HBs-S antigen-dependent enhancement of HBV infection

HBs-S antigen-dependent enhancement of HBV infection

Targeting Host Innate and Adaptive Immunity to Achieve the Functional Cure of Chronic Hepatitis B

Pathogenesis and Immune Response Caused by Vector-Borne and Other Viral Infections in a Tupaia Model

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