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Article ; Online: Infection-mediated immune response in SARS-CoV-2 breakthrough infection and implications for next-generation COVID-19 vaccine development.

Miyamoto, Sho / Suzuki, Tadaki

2024 Volume 42, Issue 6, Page(s) 1401–1406

Abstract: Post-vaccination infections, termed breakthrough infections, occur after the virus infection overcomes the vaccine-induced immune barrier. During the early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron wave, high ... ...

Abstract	Post-vaccination infections, termed breakthrough infections, occur after the virus infection overcomes the vaccine-induced immune barrier. During the early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron wave, high serum-neutralizing antibody titers against the Omicron variant were detected in individuals with breakthrough infections as well as those who received a third vaccine dose (i.e., booster recipients). Additionally, these cases indicated that Omicron antigens triggered an immune response that differed from that triggered by the vaccine strain before analysis of the effectiveness of new vaccines updated for the Omicron variants. Moreover, the magnitude and breadth of neutralizing antibody titers induced by breakthrough infections are correlated with the upper respiratory viral load at diagnosis and the duration between vaccination and infection, respectively. Unlike booster vaccine recipients, patients with breakthrough infections have varying durations between vaccination and infection. Accordingly, optimal booster vaccination intervals may be estimated based on the cross-neutralizing antibody response induced over time. Examination of breakthrough infection cases has provided valuable insights that could not be yielded by only examining vaccinated individuals alone. These insights include estimates of vaccine-induced immunity against SARS-CoV-2 variants and the various factors related to the clinical status. This review describes the immune response elicited by breakthrough infections; specifically, it discusses factors that affect the magnitude and breadth of serum antibody titers as well as the appropriate booster vaccination strategy. This review provides key aspects that could contribute to developing next-generation COVID-19 vaccines through breakthrough infection cases.
MeSH term(s)	Humans ; COVID-19 Vaccines ; COVID-19/prevention & control ; Breakthrough Infections ; SARS-CoV-2 ; Antibodies, Neutralizing ; Vaccine Development ; Immunity ; Antibodies, Viral
Chemical Substances	COVID-19 Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2024-02-02
Publishing country	Netherlands
Document type	Review ; Journal Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2024.01.088
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Article ; Online: Hidden Challenges in Evaluating Spillover Risk of Zoonotic Viruses using Machine Learning Models

Kawasaki, Junna / Suzuki, Tadaki / Hamada, Michiaki

bioRxiv

Abstract: Machine learning models have been deployed to assess the zoonotic spillover risk of viruses by identifying their human infectivity potential. However, the scarcity of comprehensive datasets poses a major challenge, limiting the predictable range of ... ...

Abstract	Machine learning models have been deployed to assess the zoonotic spillover risk of viruses by identifying their human infectivity potential. However, the scarcity of comprehensive datasets poses a major challenge, limiting the predictable range of viruses. Our study addressed this limitation through two key strategies: constructing expansive datasets across 26 viral families and developing new models leveraging large language models pre-trained on extensive nucleotide sequences. Our approaches substantially boosted our model performance. This enhancement was particularly notable in segmented RNA viruses, which are involved with severe zoonoses but have been overlooked due to limited data availability. Furthermore, models trained on data up to 2018 displayed strong generalization capability for viruses emerging post-2018. Nonetheless, we also found remaining challenges in alerting the zoonotic potential of specific viral lineages, including SARS-CoV-2. Our study elaborates on the models and datasets for predicting viral infectivity and highlights the unresolved issues to fully exploit machine learning in preparing for future zoonotic threats.
Keywords	covid19
Language	English
Publishing date	2024-04-29
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.04.25.591033
Database	COVID19

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Article: [Development, rollout, and challenges of COVID-19 vaccines in Japan and globally].

Arashiro, Takeshi / Suzuki, Tadaki

Uirusu

2021 Volume 71, Issue 1, Page(s) 41–44

MeSH term(s)	COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Japan ; SARS-CoV-2 ; Vaccination ; Vaccines
Chemical Substances	COVID-19 Vaccines ; Vaccines
Language	Japanese
Publishing date	2021-12-08
Publishing country	Japan
Document type	Journal Article
ZDB-ID	603272-2
ISSN	0042-6857
ISSN	0042-6857
DOI	10.2222/jsv.71.41
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Article ; Online: Characterization of antibodies targeting severe fever with thrombocytopenia syndrome virus glycoprotein Gc.

Sano, Kaori / Kimura, Miyuki / Sataka, Akiko / Hasegawa, Hideki / Tani, Hideki / Suzuki, Tadaki

Archives of virology

2024 Volume 169, Issue 3, Page(s) 40

Abstract: Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its high mortality rate and increasing incidence, no vaccines or therapeutics have yet been ... ...

Abstract	Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its high mortality rate and increasing incidence, no vaccines or therapeutics have yet been approved for use against SFTS. Antibody drugs have shown promise in treating lethal infectious diseases that currently have no established treatments. In the case of SFTS, however, only a limited amount of research has been done on SFTSV-neutralizing antibodies targeting the transmembrane proteins Gn and Gc, which play critical roles in viral infection. This study focuses on the production and characterization of antibodies targeting the SFTSV Gc protein. Monoclonal antibodies against Gc were generated through immunization of mice, and their antiviral activity was evaluated. Three out of four anti-Gc antibody clones from this study demonstrated dose-dependent SFTSV neutralization activity, two of which exhibited a synergistic effect on the neutralization activity of the anti-Gn antibody clone Mab4-5. Further studies are necessary to identify key sites on the SFTSV glycoprotein and to develop novel agents as well as antibodies with diverse mechanisms of action against SFTSV.
MeSH term(s)	Animals ; Mice ; Severe Fever with Thrombocytopenia Syndrome ; Glycoproteins ; Phlebovirus ; Hemorrhagic Fevers, Viral ; Bunyaviridae Infections
Chemical Substances	Glycoproteins
Language	English
Publishing date	2024-02-03
Publishing country	Austria
Document type	Journal Article
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-024-05968-x
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Article: Investigation of Molecular Mechanism of JC virus Viroporin Activity.

Suzuki, Tadaki

Uirusu

2015 Volume 65, Issue 1, Page(s) 135–144

Abstract: Viroporins are small and hydrophobic viral proteins that form pores on host cell membranes, and their expression can increase the permeability of cellular membranes and the production of progeny virus particles. JC virus (JCV) is the causative agent of ... ...

Abstract	Viroporins are small and hydrophobic viral proteins that form pores on host cell membranes, and their expression can increase the permeability of cellular membranes and the production of progeny virus particles. JC virus (JCV) is the causative agent of progressive multifocal leukoenchephalopathy (PML). We demonstrate that JCV Agno, which is the small and hydrophobic protein, andincreases the plasma membrane permeability and virion release, acts as a viroporin. We also demonstrate that an interaction of Agno with a host cellular protein regulates the viroporin activity of Agno. These findings indicate a new paradigm in virus-host interactions regulating viroporin activity and viral replication.
MeSH term(s)	Cell Membrane Permeability ; Host-Pathogen Interactions/physiology ; Humans ; JC Virus/genetics ; JC Virus/pathogenicity ; JC Virus/physiology ; Leukoencephalopathy, Progressive Multifocal/virology ; Membrane Lipids/metabolism ; Viral Regulatory and Accessory Proteins/chemistry ; Viral Regulatory and Accessory Proteins/physiology ; Virion/metabolism ; Virus Replication
Chemical Substances	Membrane Lipids ; Viral Regulatory and Accessory Proteins ; agnoprotein, polyomavirus
Language	Japanese
Publishing date	2015
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	603272-2
ISSN	0042-6857
ISSN	0042-6857
DOI	10.2222/jsv.65.135
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Article ; Online: Insights into Pathology and Pathogenesis of Coronavirus Disease 2019 from a Histopathological and Immunological Perspective.

Iida, Shun / Arashiro, Takeshi / Suzuki, Tadaki

JMA journal

2021 Volume 4, Issue 3, Page(s) 179–186

Abstract: Since the first case of COVID-19 was reported in Wuhan, China, in December 2019, the SARS-CoV-2 epidemic has spread all over the world and has become a significant public health issue. The development of treatments for COVID-19 is currently in progress; ... ...

Abstract	Since the first case of COVID-19 was reported in Wuhan, China, in December 2019, the SARS-CoV-2 epidemic has spread all over the world and has become a significant public health issue. The development of treatments for COVID-19 is currently in progress; however, their effects remain limited, and the development of more effective therapeutics is desired. Thus, sufficient understanding of the pathophysiology of COVID-19 is essential to develop effective therapeutics for this disease. Pathological analyses in particular play an important role to demonstrate the causal link between an infectious disease and the pathogen and elucidate the mechanism of pathogenesis. As per pathological analyses to date, respiratory organs are identified as the major affected organs in most COVID-19 cases; also, various lesions were noted in other organs. Further, there have been increasing reports that show that the immune responses of the host contribute to the deterioration of the pathological condition of COVID-19, and a novel concept of MIS-C/MIS-A is also being established. Thus, in this article, we have provided an overview of the pathology of COVID-19 from a histopathological and immunological perspective focusing on the mechanisms of COVID-19 pathogenesis.
Language	English
Publishing date	2021-07-13
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	3053329-6
ISSN	2433-3298 ; 2433-328X
ISSN (online)	2433-3298
ISSN	2433-328X
DOI	10.31662/jmaj.2021-0041
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Article ; Online: Draft genome sequence of

Okutani, Akiko / Taira, Masakatsu / Iida, Shun / Park, Eun-Sil / Tokuyoshi, Mikuni / Watari, Yuya / Suzuki, Tadaki / Maeda, Ken

Microbiology resource announcements

2024 , Page(s) e0126923

Abstract: We report a draft genome sequence ... ...

Abstract	We report a draft genome sequence of
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ISSN	2576-098X
ISSN (online)	2576-098X
DOI	10.1128/mra.01269-23
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Article: Mice, myeloid cells, and dengue: a new model for unraveling vascular leakage mysteries.

Kurosu, Takeshi / Sakai, Yusuke / Ami, Yasusi / Shimojima, Masayuki / Yoshikawa, Tomoki / Fukushi, Shuetsu / Nagata, Noriyo / Suzuki, Tadaki / Ebihara, Hideki / Saijo, Masayuki

Frontiers in microbiology

2024 Volume 15, Page(s) 1367672

Abstract: Introduction: Severe dengue is thought to be caused by an excessive host immune response.: Methods: To study the pathogenesis of severe dengue, we developed a novel model using LysM Cre: Results: Although dengue virus (DENV) clinical isolates were ...

Abstract	Introduction: Severe dengue is thought to be caused by an excessive host immune response. Methods: To study the pathogenesis of severe dengue, we developed a novel model using LysM Cre Results: Although dengue virus (DENV) clinical isolates were not virulent in LysM Cre Discussion: These observations suggest that myeloid cell infection is sufficient to trigger cytokine storm-induced vascular leakage. This model can refine the factors involved in the pathology of severe dengue leading to vascular leakage.
Language	English
Publishing date	2024-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2024.1367672
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Article ; Online: Development of a Mouse-Adapted Reporter SARS-CoV-2 as a Tool for Two-Photon In Vivo Imaging.

Ueki, Hiroshi / Kiso, Maki / Furusawa, Yuri / Iida, Shun / Yamayoshi, Seiya / Nakajima, Noriko / Imai, Masaki / Suzuki, Tadaki / Kawaoka, Yoshihiro

Viruses

2024 Volume 16, Issue 4

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia. Although many studies using mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia. Although many studies using mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy (TPEM) is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated a mouse-adapted strain of SARS-CoV-2 (named MASCV2-p25) and demonstrated its efficient replication in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed the severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6 mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent protein-encoding gene Venus into MASCV2-p25 and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia. In addition, the TPEM of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two-photon in vivo imaging studies of the pathogenesis of severe COVID-19 pneumonia.
MeSH term(s)	Animals ; Mice ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; SARS-CoV-2/physiology ; COVID-19/virology ; Mice, Inbred C57BL ; Lung/virology ; Lung/pathology ; Lung/diagnostic imaging ; Disease Models, Animal ; Humans ; Genes, Reporter ; Virus Replication
Language	English
Publishing date	2024-03-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16040537
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Article ; Online: A bivalent outer membrane vesicle-based intranasal vaccine to prevent infection of periodontopathic bacteria

Nakao, Ryoma / Hirayama, Satoru / Yamaguchi, Takehiro / Senpuku, Hidenobu / Hasegawa, Hideki / Suzuki, Tadaki / Akeda, Yukihiro / Ohnishi, Makoto

Vaccine.

2023

Abstract: Periodontal disease has become a serious public health problem, not only causing tooth loss, but also inducing chronic disorders of extra-oral organs. The present study assessed an intranasal vaccine strategy to prevent periodontal disease using outer ... ...

Abstract	Periodontal disease has become a serious public health problem, not only causing tooth loss, but also inducing chronic disorders of extra-oral organs. The present study assessed an intranasal vaccine strategy to prevent periodontal disease using outer membrane vesicles (OMVs) of two major periodontopathic bacteria, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa). We compared the morphology, composition, and immune activity between OMVs of Pg strain ATCC 33277 and Aa strain Y4. Aa OMVs had a smoother surface and stronger lipid A activity compared to Pg OMVs. The in vitro immune activity elicited by Aa OMVs in macrophage-like cells was remarkably stronger than that of Pg OMVs. Intranasal immunization of mice with Aa OMVs alone resulted in robust, humoral immune responses in blood and saliva. Despites the intrinsically low mucosal immunogenicity of Pg OMVs alone, using Aa OMVs as a mucosal adjuvant strongly enhanced Pg-specific immune responses, resulting in both serum IgG and salivary IgA, both of which aggregated Pg and Aa cells. Furthermore, Aa OMVs were found to be a more potent mucosal adjuvant than Poly(I:C) in the context of enhancing the production of Pg-specific IgG (especially IgG2a) and IgA. In addition, in a randomized, blinded study, mice oral challenged with Pg and Aa after intranasal immunization with Pg OMVs and Aa OMVs had significantly decreased numbers of both microorganisms compared to mock-immunized mice. Furthermore, in an intracerebral injection mouse model, there were no serious adverse effects on the brain even after administrating a dose of OMVs as same as that used for intranasal administration. Taken together, the bivalent OMV intranasal vaccine may be effective in preventing colonization of periodontopathic bacteria in the oral cavity and related systemic disorders associated with periodontal diseases.
Keywords	Actinobacillus actinomycetemcomitans ; Porphyromonas gingivalis ; adjuvants ; blood serum ; brain ; immunization ; immunogenicity ; immunoglobulin G ; intranasal administration ; lipid A ; mice ; models ; mouth ; periodontal diseases ; public health ; saliva ; vaccines ; Outer membrane vesicles (OMVs) ; periodontal disease ; Aggregatibacter actinomycetemcomitans
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2023.05.058
Database	NAL-Catalogue (AGRICOLA)

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