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Article: Humoral immunity for durable control of SARS-CoV-2 and its variants.

Kotaki, Ryutaro / Moriyama, Saya / Takahashi, Yoshimasa

2023 Volume 43, Issue 1, Page(s) 4

Abstract: The coronavirus disease 2019 (COVID-19) pandemic is ongoing because of the repeated emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, highlighting the importance of developing vaccines for variants that may continue to ... ...

Abstract	The coronavirus disease 2019 (COVID-19) pandemic is ongoing because of the repeated emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, highlighting the importance of developing vaccines for variants that may continue to emerge. In the present review, we discuss humoral immune responses against SARS-CoV-2 with a focus on the antibody breadth to the variants. Recent studies have revealed that the temporal maturation of humoral immunity improves the antibody potency and breadth to the variants after infection or vaccination. Repeated vaccination or infection further accelerates the expansion of the antibody breadth. Memory B cells play a central role in this phenomenon, as the reactivity of the B-cell antigen receptor (BCR) on memory B cells is a key determinant of the antibody potency and breadth recalled upon vaccination or infection. The evolution of memory B cells remarkably improves the reactivity of BCR to antigenically distinct Omicron variants, to which the host has never been exposed. Thus, the evolution of memory B cells toward the variants constitutes an immunological basis for the durable and broad control of SARS-CoV-2 variants.
Language	English
Publishing date	2023-01-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2051471-2
ISSN	1880-9693 ; 0389-4290
ISSN	1880-9693 ; 0389-4290
DOI	10.1186/s41232-023-00255-9
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Zs.B 2929: Show issues

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Article ; Online: Abaloparatide promotes bone repair of vertebral defects in ovariectomized rats by increasing bone formation.

Makino, Akito / Hasegawa, Tomoka / Yamamoto, Tomomaya / Takagi, Hideko / Takahashi, Yoshimasa / Miyakoshi, Naohisa / Amizuka, Norio

Bone

2024 Volume 182, Page(s) 117056

Abstract: Osteoporotic vertebral fracture (OVF) is the most common type of osteoporotic fracture and is associated with immobility and mortality. Bone anabolic agents, such as abaloparatide (ABL), are usually administered to patients with OVF to prevent subsequent ...

Abstract	Osteoporotic vertebral fracture (OVF) is the most common type of osteoporotic fracture and is associated with immobility and mortality. Bone anabolic agents, such as abaloparatide (ABL), are usually administered to patients with OVF to prevent subsequent fractures. Although several studies have shown that bone anabolic agents promote healing of long bone fractures, there is little evidence of their healing effect on vertebral bone fractures. In the present study, we investigated the effect of ABL on vertebral bone defects using ovariectomized (OVX) rats with vertebral body drill-hole defects, an animal model of OVF. Eight-week-old female Sprague-Dawley rats were subjected to OVX, followed by the 32-36 days of bone depletion period, once-daily subcutaneous ABL was administered to OVX rats at a dose of 30 μg/kg for a maximum of 6 weeks from the day of the vertebral defect surgery. We found that ABL significantly increased bone mineral content and improved trabecular structural parameters at the vertebral defect site. Moreover, ABL significantly increased bone strength of the defected vertebrae. Bone histochemical analysis revealed formation of thick trabecular bone networks at the defect site after ABL administration, consistent with an improvement in trabecular structural parameters by ABL. ABL increased ALPase- and PHOSPHO1-positive osteoblastic cells and ALPase/PCNA double-positive cells, indicating enhanced preosteoblast proliferation as well as bone formation at the defect site. On the other hand, ABL did not affect the number of cathepsin K-positive osteoclasts per bone surface, suggesting that ABL did not promote excessive bone resorption. Our findings suggest that ABL is useful not only for preventing secondary vertebral fractures but also for promoting bone healing in OVF.
MeSH term(s)	Humans ; Rats ; Female ; Animals ; Osteogenesis ; Rats, Sprague-Dawley ; Anabolic Agents/pharmacology ; Spine ; Osteoporotic Fractures/drug therapy ; Spinal Fractures ; Bone Density ; Ovariectomy ; Parathyroid Hormone-Related Protein
Chemical Substances	abaloparatide (AVK0I6HY2U) ; Anabolic Agents ; Parathyroid Hormone-Related Protein
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2024.117056
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Zs.A 1571: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 332: Show issues

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Article ; Online: [The Applications of qNMR in Drug Quality Control].

Ena, Eri / Asai, Yumi / Hasebe, Takashi / Oe, Hiroshi / Hirose, Shuichi / Takahashi, Yoshimasa

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2024 Volume 144, Issue 4, Page(s) 381–385

Abstract: NMR is well known as one of the most important methods for elucidating the structure of organic compounds. Furthermore, it has recently been recognized as a powerful tool for quantitative analysis. The quantitative NMR (qNMR) has become an official ... ...

Abstract	NMR is well known as one of the most important methods for elucidating the structure of organic compounds. Furthermore, it has recently been recognized as a powerful tool for quantitative analysis. The quantitative NMR (qNMR) has become an official analytical method described in detail in the Japanese Pharmacopoeia. And today, it is widely applied in drug development. The qNMR method offers many new advantages over traditional and conventional quantitative analysis methods. For example, this method requires only a few milligrams of the analyte and allows absolute quantitation of the analyte without using a qualified reference standard as a control sample. Then, it can be easily applied to most chemicals without expending significant time and resources on method development. In addition, residual solvent can be determined using qNMR methods. The peak area of an NMR spectrum is directly proportional to the number of protons contributing to the resonance. Based on this principle, the residual solvent can be determined by counting the signal corresponding to the residual solvent in the sample solution. We have applied qNMR as an alternative to GC. Thus, qNMR is an innovative and promising analytical technique that is expected to make significant progress in the future. Recently, the analytical research and quality control departments have been working together to expand this technology to a wide range of areas in the pharmaceutical industry.
MeSH term(s)	Magnetic Resonance Spectroscopy/methods ; Quality Control ; Reference Standards ; Drug Industry ; Solvents
Chemical Substances	Solvents
Language	Japanese
Publishing date	2024-04-01
Publishing country	Japan
Document type	English Abstract ; Journal Article
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.23-00151-6
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Zs.A 643: Show issues

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Article ; Online: Immune responses related to the immunogenicity and reactogenicity of COVID-19 mRNA vaccines.

Matsumura, Takayuki / Takano, Tomohiro / Takahashi, Yoshimasa

International immunology

2022 Volume 35, Issue 5, Page(s) 213–220

Abstract: Vaccination for the prevention of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is considered the most promising approach to control the pandemic of coronavirus disease 2019 (COVID-19). Although various COVID-19 vaccines ... ...

Abstract	Vaccination for the prevention of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is considered the most promising approach to control the pandemic of coronavirus disease 2019 (COVID-19). Although various COVID-19 vaccines have been developed worldwide using several modalities, the vaccines that have shown the highest efficacy to date are mRNA vaccines. Despite their extensive usage, the mechanisms that stimulate the immune responses associated with their immunogenicity and reactogenicity remain largely unknown. In this review, we summarize and discuss current knowledge on immune responses to COVID-19 mRNA vaccines, including potential immune responses and correlating factors underlying the immunogenicity and reactogenicity of mRNA vaccines. We also describe recent trends in the optimization of lipid nanoparticles and vaccination routes. Further understanding of vaccine-elicited immune responses will guide the development of more effective and safe vaccines.
MeSH term(s)	Humans ; COVID-19 Vaccines/adverse effects ; COVID-19/prevention & control ; SARS-CoV-2 ; RNA, Messenger/genetics ; mRNA Vaccines ; Antibodies, Viral
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; mRNA Vaccines ; Antibodies, Viral
Language	English
Publishing date	2022-12-24
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxac064
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Zs.A 2619: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 70: Show issues

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Article ; Online: Hide and seek: interplay between influenza viruses and B cells.

Kuraoka, Masayuki / Adachi, Yu / Takahashi, Yoshimasa

International immunology

2020 Volume 32, Issue 9, Page(s) 605–611

Abstract: Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza ... ...

Abstract	Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza viruses and are targeted by broadly protective antibodies. A goal for the next-generation influenza vaccines is to stimulate B-cell responses against such conserved epitopes in order to provide broad protection against divergent influenza viruses. Broadly protective B cells, however, are not easily activated by HA antigens with native structure, because the virus has multiple strategies to escape from the humoral immune responses directed to the conserved epitopes. One such strategy is to hide the conserved epitopes from the B-cell surveillance by steric hindrance. Technical advancement in the analysis of the human B-cell antigen receptor (BCR) repertoire has dissected the BCRs to HA epitopes that are hidden in the native structure but are targeted by broadly protective antibodies. We describe here the characterization and function of broadly protective antibodies and strategies that enable B cells to seek these hidden epitopes, with potential implications for the development of universal influenza vaccines.
MeSH term(s)	B-Lymphocytes/immunology ; Hemagglutinins/immunology ; Humans ; Orthomyxoviridae/immunology ; Receptors, Antigen, B-Cell/immunology
Chemical Substances	Hemagglutinins ; Receptors, Antigen, B-Cell
Language	English
Publishing date	2020-04-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxaa028
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Zs.A 2619: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 70: Show issues

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Article: Memory B Cells in Local and Systemic Sites.

Moriyama, Saya / Adachi, Yu / Tonouchi, Keisuke / Takahashi, Yoshimasa

Advances in experimental medicine and biology

2020 Volume 1254, Page(s) 55–62

Abstract: Memory B cells are a key cellular component of the protective humoral responses to infectious pathogens. Most of our knowledge of memory B-cell responses comes from studies using mono-epitopic model antigens that elicit systemic humoral responses ... ...

Abstract	Memory B cells are a key cellular component of the protective humoral responses to infectious pathogens. Most of our knowledge of memory B-cell responses comes from studies using mono-epitopic model antigens that elicit systemic humoral responses dominated by canonical B-cell antigen receptors. This approach successfully dissected the systemic responses of memory B cells and greatly advanced our understanding of memory B-cell formation, maintenance, and reactivation to re-invading antigens in the secondary lymphoid organs. However, the canonical memory B-cell responses fail to fully recapitulate the heterogeneity of the protective memory responses. Indeed, accumulating studies using "natural" antigens and live pathogens have uncovered new aspects of memory B-cell responses, which are achieved by memory B cells with different phenotypes, tissue residence, and responsiveness to antigen stimulation. Such non-canonical memory B-cell responses are frequently observed in local sites where live pathogens initially infect and replicate. Importantly, the local memory B-cell responses often serve as the first line of defense against re-infecting pathogens, thereby playing an essential role in controlling the pathogens. Here, we provide a comprehensive overview of the systemic and local memory B-cell responses in the humoral protective immunity against pathogens.
MeSH term(s)	Animals ; Antigens ; B-Lymphocytes ; Humans ; Immunity, Humoral ; Immunologic Memory ; Receptors, Antigen, B-Cell
Chemical Substances	Antigens ; Receptors, Antigen, B-Cell
Language	English
Publishing date	2020-04-22
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-981-15-3532-1_5
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Article ; Online: Saliva as a useful tool for evaluating upper mucosal antibody response to influenza.

Tsunetsugu-Yokota, Yasuko / Ito, Sayaka / Adachi, Yu / Onodera, Taishi / Kageyama, Tsutomu / Takahashi, Yoshimasa

PloS one

2022 Volume 17, Issue 2, Page(s) e0263419

Abstract: Mucosal immunity plays a crucial role in controlling upper respiratory infections, including influenza. We established a quantitative ELISA to measure the amount of influenza virus-specific salivery IgA (sIgA) and salivary IgG (sIgG) antibodies using a ... ...

Abstract	Mucosal immunity plays a crucial role in controlling upper respiratory infections, including influenza. We established a quantitative ELISA to measure the amount of influenza virus-specific salivery IgA (sIgA) and salivary IgG (sIgG) antibodies using a standard antibody broadly reactive to the influenza A virus. We then analyzed saliva and serum samples from seven individuals infected with the A(H1N1)pdm09 influenza virus during the 2019-2020 flu seasons. We detected an early (6-10 days post-infection) increase of sIgA in five of the seven samples and a later (3-5 weeks) increase of sIgG in six of the seven saliva samples. Although the conventional parenteral influenza vaccine did not induce IgA production in saliva, vaccinated individuals with a history of influenza infection had higher basal levels of sIgA than those without a history. Interestingly, we observed sIgA and sIgG in an asymptomatic individual who had close contact with two influenza cases. Both early mucosal sIgA secretion and late systemically induced sIgG in the mucosal surface may protect against virus infection. Despite the small sample size, our results indicate that the saliva test system can be useful for analyzing upper mucosal immunity in influenza.
MeSH term(s)	Adult ; Aged ; Antibodies, Viral/analysis ; Antibodies, Viral/metabolism ; Antibody Formation ; Cohort Studies ; Female ; History, 21st Century ; Humans ; Immunity, Mucosal/physiology ; Immunoglobulin A/analysis ; Immunoglobulin A/metabolism ; Immunoglobulin A, Secretory/analysis ; Immunoglobulin A, Secretory/metabolism ; Immunoglobulin G/analysis ; Immunoglobulin G/metabolism ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza Vaccines/therapeutic use ; Influenza, Human/diagnosis ; Influenza, Human/immunology ; Influenza, Human/prevention & control ; Japan ; Longitudinal Studies ; Male ; Predictive Value of Tests ; Prognosis ; Saliva/chemistry ; Saliva/immunology ; Saliva/metabolism ; Young Adult
Chemical Substances	Antibodies, Viral ; Immunoglobulin A ; Immunoglobulin A, Secretory ; Immunoglobulin G ; Influenza Vaccines
Language	English
Publishing date	2022-02-07
Publishing country	United States
Document type	Historical Article ; Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0263419
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Article ; Online: Assessment of Fcγ receptor-dependent binding of influenza hemagglutinin vaccine-induced antibodies in a non-human primate model.

Masuta, Yuji / Takahama, Shokichi / Nogimori, Takuto / Moriyama, Saya / Takahashi, Yoshimasa / Yamamoto, Takuya

iScience

2022 Volume 25, Issue 10, Page(s) 105085

Abstract: Several cross-protective antibodies that recognize a broad range of influenza A virus (IAV) strains are known to have functions in virus elimination such as Fcγ receptor (FcγR)-effector function and neutralizing activity against the head region. Although ...

Abstract	Several cross-protective antibodies that recognize a broad range of influenza A virus (IAV) strains are known to have functions in virus elimination such as Fcγ receptor (FcγR)-effector function and neutralizing activity against the head region. Although few studies have used primary cells as effector cells, the FcγR-effector function was evaluated after isolating each cell subset. Herein, we established an original assay system to evaluate purified FI6 IgG-mediated binding to hemagglutinin (HA)-expressing cells by flow cytometry using peripheral blood mononuclear cells from cynomolgus macaques. In addition, we evaluated the FcγR-effector function of IAV vaccine-induced anti-HA antibodies in cynomolgus macaques after administering the split vaccine. We found several cell types, mainly classical monocytes, bound to HA-expressing target cells in an FcγR-dependent manner, that were dominant in the binding of the cell population. Thus, this assay system could facilitate the development of a universal influenza vaccine.
Language	English
Publishing date	2022-09-06
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.105085
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Article ; Online: High-throughput isolation of SARS-CoV-2 nucleocapsid antibodies for improved antigen detection.

Fujisawa, Mizuki / Adachi, Yu / Onodera, Taishi / Shiwa-Sudo, Nozomi / Iwata-Yoshikawa, Naoko / Nagata, Noriyo / Suzuki, Tadaki / Takeoka, Shinji / Takahashi, Yoshimasa

Biochemical and biophysical research communications

2023 Volume 673, Page(s) 114–120

Abstract: SARS-CoV-2 nucleocapsid protein (NP) is the main target for COVID-19-diagnostic PCR and antigen rapid diagnostic tests (Ag-RDTs). Ag-RDTs are more convenient than PCR tests for point-of-care testing or self-testing to identify the SARS-CoV-2 antigen. The ...

Abstract	SARS-CoV-2 nucleocapsid protein (NP) is the main target for COVID-19-diagnostic PCR and antigen rapid diagnostic tests (Ag-RDTs). Ag-RDTs are more convenient than PCR tests for point-of-care testing or self-testing to identify the SARS-CoV-2 antigen. The sensitivity and specificity of this method depends mainly on the affinity and specificity of NP-binding antibodies; therefore, antigen-antibody binding is key elements for the Ag-RDTs. Here, we applied the high-throughput antibody isolation platform that has been utilized to isolate therapeutic antibodies against rare epitopes. Two NP antibodies were identified to recognize non-overlapping epitopes with high affinity. One antibody specifically binds to SARS-CoV-2 NP, and the other rapidly and tightly binds to SARS-CoV-2 NP with cross-reactivity to SARS-CoV NP. Furthermore, these antibodies were compatible with a sandwich enzyme-linked immunosorbent assay that exhibited enhanced sensitivity for NP detection compared to the previously isolated NP antibodies. Thus, the NP antibody pair is applicable to more sensitive and specific Ag-RDTs, highlighting the utility of a high-throughput antibody isolation platform for diagnostics development.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/diagnosis ; Nucleocapsid ; Antibodies, Viral ; Epitopes ; Sensitivity and Specificity
Chemical Substances	Antibodies, Viral ; Epitopes
Language	English
Publishing date	2023-06-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.06.067
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Article ; Online: Structural basis for cross-group recognition of an influenza virus hemagglutinin antibody that targets postfusion stabilized epitope.

Tonouchi, Keisuke / Adachi, Yu / Suzuki, Tateki / Kuroda, Daisuke / Nishiyama, Ayae / Yumoto, Kohei / Takeyama, Haruko / Suzuki, Tadaki / Hashiguchi, Takao / Takahashi, Yoshimasa

PLoS pathogens

2023 Volume 19, Issue 8, Page(s) e1011554

Abstract: Plasticity of influenza virus hemagglutinin (HA) conformation increases an opportunity to generate conserved non-native epitopes with unknown functionality. Here, we have performed an in-depth analysis of human monoclonal antibodies against a stem-helix ... ...

Abstract	Plasticity of influenza virus hemagglutinin (HA) conformation increases an opportunity to generate conserved non-native epitopes with unknown functionality. Here, we have performed an in-depth analysis of human monoclonal antibodies against a stem-helix region that is occluded in native prefusion yet exposed in postfusion HA. A stem-helix antibody, LAH31, provided IgG Fc-dependent cross-group protection by targeting a stem-helix kinked loop epitope, with a unique structure emerging in the postfusion state. The structural analysis and molecular modeling revealed key contact sites responsible for the epitope specificity and cross-group breadth that relies on somatically mutated light chain. LAH31 was inaccessible to the native prefusion HA expressed on cell surface; however, it bound to the HA structure present on infected cells with functional linkage to the Fc-mediated clearance. Our study uncovers a novel non-native epitope that emerges in the postfusion HA state, highlighting the utility of this epitope for a broadly protective antigen design.
MeSH term(s)	Humans ; Antibodies, Neutralizing ; Antibodies, Viral/chemistry ; Antibodies, Viral/metabolism ; Epitopes ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry ; Hemagglutinin Glycoproteins, Influenza Virus/metabolism ; Influenza, Human ; Orthomyxoviridae
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Hemagglutinin Glycoproteins, Influenza Virus
Language	English
Publishing date	2023-08-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011554
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