Guinea pig immunoglobulin VH and VL naïve repertoire analysis

Matsuzawa, Shun; Isobe, Masaharu; Kurosawa, Nobuyuki

doi:10.1371/journal.pone.0208977

Cited by 3 publications

(3 citation statements)

References 48 publications

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“…This might explain the contradictory data previously published by Vassilieva et al, in which flagellin functionalization enhanced the Env-specific humoral responses to Env-VLP immunization in guinea pigs [28]. Guinea pigs are phylogenetically distant from mice and have higher immunoglobulin combinatorial diversity [31]. These animals are broadly used in HIV studies due to their ability to induce HIV-Env neutralizing antibodies [32], which might indicate a stronger immunogenicity of HIV-Env in guinea pigs than in mice.…”

Section: Resultsmentioning

confidence: 99%

Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines

et al. 2019

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The great advantage of virus-like particle (VLP) nano-vaccines is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter viral proteins in their natural conformation. “Wild-type” viral nanoparticles can be further genetically or biochemically functionalized with biomolecules (antigens and adjuvants). Flagellin is a potent inducer of innate immunity and it has demonstrated adjuvant effectiveness due to its affinity for toll-like receptor 5 (TLR5). In contrast to most TLR ligands, flagellin is a protein and can induce an immune response against itself. To avoid side-effects, we incorporated a less inflammatory and less immunogenic form of flagellin as an adjuvant into HIV-based nanoparticle B-cell-targeting vaccines that display either the HIV-1 envelope protein (Env) or a model antigen, hen egg lysozyme (HEL). While flagellin significantly enhanced HEL-specific IgG responses, anti-Env antibody responses were suppressed. We demonstrated that flagellin did not activate B-cells directly in vitro, but might compete for CD4+ T-cell help in vivo. Therefore, we hypothesize that in the context of VLP-based B-cell nano-vaccines, flagellin serves as an antigen itself and may outcompete a less immunogenic antigen with its antibody response. In contrast, in combination with a strong immunogen, the adjuvant activity of flagellin may dominate over its immunogenicity.

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Section: Resultsmentioning

confidence: 99%

Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines

et al. 2019

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“…We have recently shown that guinea pigs can be a novel source of monoclonal antibodies. Because guinea pigs have a completely different B-cell repertoire than mice, this animal may offer novel solutions for the production of high-affinity antibodies against CoV-2-NP that cannot be produced in mice [ 14 , 15 ]. In this study, we developed mAbs from guinea pigs immunized with CoV-2-NP and selected highly specific epitope-characterized mAbs suitable for the detection of CoV-2-NP.…”

Section: Introductionmentioning

confidence: 99%

The development of a highly sensitive and quantitative SARS-CoV-2 rapid antigen test applying newly developed monoclonal antibodies to an automated chemiluminescent flow-through membrane immunoassay device

Nishimura,

Kitazawa,

Kawahata

et al. 2023

BMC Immunol

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Background Rapid and accurate diagnosis of individuals with SARS-CoV-2 infection is an effective way to prevent and control the spread of COVID-19. Although the detection of SARS‐CoV‐2 viral RNA by RT‐qPCR is the gold standard for COVID-19 testing, the use of antigen-detecting rapid diagnostic tests (Ag-RDTs) is emerging as a complementary surveillance tool as Omicron case numbers skyrocket worldwide. However, the results from Ag-RDTs are less accurate in individuals with low viral loads. Results To develop a highly sensitive and accurate Ag-RDT, 90 monoclonal antibodies were raised from guinea pigs immunized with SARS CoV-2 nucleocapsid protein (CoV-2-NP). By applying a capture antibody recognizing the structural epitope of the N-terminal domain of CoV-2-NP and a detection antibody recognizing the C-terminal tail of CoV-2-NP to an automated chemiluminescence flow-through membrane immunoassay device, we developed a novel Ag-RDT, CoV-2-POCube. The CoV-2-POCube exclusively recognizes CoV-2-NP variants but not the nucleocapsid proteins of other human coronaviruses. The CoV-2-POCube achieved a limit of detection sensitivity of 0.20 ~ 0.66 pg/mL of CoV-2-NPs, demonstrating more than 100 times greater sensitivity than commercially available SARS-CoV-2 Ag-RDTs. Conclusions CoV-2-POCube has high analytical sensitivity and can detect SARS-CoV-2 variants in 15 min without observing the high-dose hook effect, thus meeting the need for early SARS-CoV-2 diagnosis with lower viral load. CoV-2-POCube is a promising alternative to currently available diagnostic devices for faster clinical decision making in individuals with suspected COVID-19 in resource-limited settings.

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“…We recently showed that guinea pigs can be a novel source of monoclonal antibodies. Because guinea pigs have a completely different B-cell repertoire than mice, this animal may offer novel solutions for producing high-a nity antibodies against CoV-2-NP that cannot be produced in mice [13] [14]. In this study, we developed mAbs from guinea pigs immunized with CoV-2-NP and highly speci c epitope-characterized mAbs suitable for the detection of CoV-2-NP were selected.…”

mentioning

confidence: 99%

The development of a highly sensitive and quantitative SARS-CoV-2 rapid antigen test applying newly developed monoclonal antibodies to an automated chemiluminescent flow-through membrane immunoassay device

Nishimura

Kitazawa²,

Kawahata³

et al. 2022

Preprint

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Background The rapid and accurate diagnosis of individuals with SARS-CoV-2 infection is an effective way to prevent and control the spread of COVID-19. Although the detection of SARS-CoV‐2 viral RNA by RT‐qPCR is the gold standard for COVID‐19 testing, the use of antigen-detecting rapid diagnostic tests (Ag-RDTs) is emerging as a complementary surveillance tool as Omicron case numbers skyrocket worldwide. However, the results from Ag-RDTs are less accurate for individuals with low viral loads. Methods To develop a more sensitive and accurate Ag-RDT, we screened a total of 90 candidate monoclonal antibodies (mAbs) obtained from guinea pigs immunized with SARS-CoV-2 nucleocapsid protein (CoV-2-NP), and a highly specific epitope-characterized mAb set suitable for detecting the antigen was selected. By applying the mAb set to an automated chemiluminescence flow-through membrane immunoassay device, we developed a highly sensitive and quantitative Ag-RDT, CoV-2-POCube. Results CoV-2-POCube exclusively recognizes a variety of CoV-2-NP variants but not the nucleocapsid proteins of SARS-CoV and other human coronaviruses. CoV-2-POCube achieved a limit of detection sensitivity of 0.20 ~ 0.66 pg/mL of a variety of CoV-2-NP variants, showing over 100 times greater sensitivity than commercially airable SARS-CoV-2 Ag-RDTs. Conclusion CoV-2-POCube is a promising alternative to currently available diagnostic devices for faster clinical decision-making in individuals with suspected COVID-19 in limited-resource settings.

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Guinea pig immunoglobulin VH and VL naïve repertoire analysis

Cited by 3 publications

References 48 publications

Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines

Advantages and Limitations of Integrated Flagellin Adjuvants for HIV-Based Nanoparticle B-Cell Vaccines

The development of a highly sensitive and quantitative SARS-CoV-2 rapid antigen test applying newly developed monoclonal antibodies to an automated chemiluminescent flow-through membrane immunoassay device

The development of a highly sensitive and quantitative SARS-CoV-2 rapid antigen test applying newly developed monoclonal antibodies to an automated chemiluminescent flow-through membrane immunoassay device

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