TLR-9 agonist and CD40-targeting vaccination induces HIV-1 envelope-specific B cells with a diversified immunoglobulin repertoire in humanized mice
The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to ef...
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| Published in | PLoS pathogens Vol. 16; no. 11; p. e1009025 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
30.11.2020
Public Library of Science (PLoS) |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1553-7374 1553-7366 1553-7374 |
| DOI | 10.1371/journal.ppat.1009025 |
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| Abstract | The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG
+
hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS
+
memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans. |
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| AbstractList | The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG.sup.+ hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS.sup.+ memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans. Correlates of protection also included the generation of Env-specific T-cell responses and showed the importance of IgG isotype and ADCC (antibody-dependent cell-mediated cytotoxicity) of the antibody responses [7–10]. The anti-human CD40 antibody fused via a flexible linker to the heavy (H)-chain C terminus to codon-optimized Env gp140 protein from the clade C HIV-1 96ZM651 (called ZM96) strain has been tested in NHPs primed with a replication-competent NYVAC-KC vaccinia virus vector encoding HIV-1 Gag, Nef, Pol, and Env gp140 sequences [16]. Results TLR9 stimulation by CpG and CD40-targeting vaccination cooperatively induces B-cell maturation and the emergence of IgG+ B cells, increases CD40 expression on human antigen-presenting cells, and expansion of memory T cells in vaccinated hu-mice We and others have shown that a functional human immune system that includes human DCs and T and B cells is developed in immunodeficient mice transplanted with human fetal liver-derived CD34+ cells. Mann-Whitney U-tests were used for comparisons between immunized and non-immunized hu-mice. *p < 0.05. https://doi.org/10.1371/journal.ppat.1009025.g002 CpG/CD vaccination strategies elicit HIV-1 Env-specific IgG+ hu-B cells We next assessed the frequency of gp140-specific IgG+ memory hu-B cells in the blood and spleen of hu-mice at 6 weeks by flow cytometry using labeled gp140ZM96 (Fig 3A and 3B). The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human Band T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected huB cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgGswitched memory huB cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific huB cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG + huB cell counterpart. Both vaccine regimens induced splenic GC-like structures containing huB and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS + memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG+ hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS+ memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans.The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG+ hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS+ memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans. The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG+ hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS+ memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans. Mice reconstituted with human hematopoietic stem cells (hu-mice) are a powerful tool for the study of human immune function in vivo and can be useful as a pre-clinical model to rank vaccination strategies. However, in hu-mice, human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. One finding of our study is that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mouse models. We further reported that the HIV-1 envelope-specific IgG+ hu-B cells elicited in hu-mice by the anti-CD40.Env vaccine used more VH3 and VH4 family genes and displayed higher rates of somatic hypermutations than the non-specific IgG+ hu-B-cell counterpart. VH3 antibodies are essential for antiviral immunity. We also showed that monitoring ICOS+ circulating Tfh cells seven days after the last booster immunization is a surrogate marker for vaccine-induced HIV-1-specific B-cell responses. Overall, we report important results, both in the setting of this hu-mouse model and for a prophylactic HIV vaccine. The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG+ hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS+ memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans. Correlates of protection also included the generation of Env-specific T-cell responses and showed the importance of IgG isotype and ADCC (antibody-dependent cell-mediated cytotoxicity) of the antibody responses [7–10]. The anti-human CD40 antibody fused via a flexible linker to the heavy (H)-chain C terminus to codon-optimized Env gp140 protein from the clade C HIV-1 96ZM651 (called ZM96) strain has been tested in NHPs primed with a replication-competent NYVAC-KC vaccinia virus vector encoding HIV-1 Gag, Nef, Pol, and Env gp140 sequences [16]. Results TLR9 stimulation by CpG and CD40-targeting vaccination cooperatively induces B-cell maturation and the emergence of IgG+ B cells, increases CD40 expression on human antigen-presenting cells, and expansion of memory T cells in vaccinated hu-mice We and others have shown that a functional human immune system that includes human DCs and T and B cells is developed in immunodeficient mice transplanted with human fetal liver-derived CD34+ cells. Mann-Whitney U-tests were used for comparisons between immunized and non-immunized hu-mice. *p < 0.05. https://doi.org/10.1371/journal.ppat.1009025.g002 CpG/CD vaccination strategies elicit HIV-1 Env-specific IgG+ hu-B cells We next assessed the frequency of gp140-specific IgG+ memory hu-B cells in the blood and spleen of hu-mice at 6 weeks by flow cytometry using labeled gp140ZM96 (Fig 3A and 3B). The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG + hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS + memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans. |
| Audience | Academic |
| Author | Ortonne, Nicolas Zurawski, Gerard Li, Guangming Mouquet, Hugo Godot, Véronique Su, Lishan Lévy, Yves Cervera-Marzal, Iñaki Gil, Laurine Tcherakian, Colas Fenwick, Craig Pantaleo, Giuseppe Cardinaud, Sylvain Zurawski, Sandra M. Milpied, Pierre Centlivre, Mireille Cheng, Liang Lelièvre, Jean-Daniel |
| AuthorAffiliation | Emory University, UNITED STATES 3 Hôpital Foch, Service de Pneumologie, Suresnes, France 1 Vaccine Research Institute, Creteil, France 12 INSERM U1222, Paris, France 5 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America 2 Inserm U955, Equipe 16, Créteil, France 9 Service of Immunology and Allergy Lausanne University Hospital, Lausanne, Switzerland 10 Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland 13 Baylor Scott and White Research Institute and INSERM U955, Dallas, Texas, United States of America 6 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America 11 Laboratory of Immunology, Department of Immunology, Institut Pasteur, Paris, France 4 Aix Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France 7 AP-HP, Hôpital Henri-Mond |
| AuthorAffiliation_xml | – name: 3 Hôpital Foch, Service de Pneumologie, Suresnes, France – name: 11 Laboratory of Immunology, Department of Immunology, Institut Pasteur, Paris, France – name: 7 AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d’Anatomopathologie, Créteil, France – name: 5 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America – name: 13 Baylor Scott and White Research Institute and INSERM U955, Dallas, Texas, United States of America – name: 4 Aix Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France – name: 1 Vaccine Research Institute, Creteil, France – name: 6 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America – name: 10 Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland – name: Emory University, UNITED STATES – name: 12 INSERM U1222, Paris, France – name: 8 AP-HP, Hôpital Henri-Mondor Albert-Chenevier, Service d’Immunologie Clinique et Maladies Infectieuses, Créteil, France – name: 2 Inserm U955, Equipe 16, Créteil, France – name: 9 Service of Immunology and Allergy Lausanne University Hospital, Lausanne, Switzerland |
| Author_xml | – sequence: 1 givenname: Véronique orcidid: 0000-0003-3557-308X surname: Godot fullname: Godot, Véronique – sequence: 2 givenname: Colas surname: Tcherakian fullname: Tcherakian, Colas – sequence: 3 givenname: Laurine surname: Gil fullname: Gil, Laurine – sequence: 4 givenname: Iñaki surname: Cervera-Marzal fullname: Cervera-Marzal, Iñaki – sequence: 5 givenname: Guangming surname: Li fullname: Li, Guangming – sequence: 6 givenname: Liang surname: Cheng fullname: Cheng, Liang – sequence: 7 givenname: Nicolas surname: Ortonne fullname: Ortonne, Nicolas – sequence: 8 givenname: Jean-Daniel orcidid: 0000-0002-8182-3628 surname: Lelièvre fullname: Lelièvre, Jean-Daniel – sequence: 9 givenname: Giuseppe surname: Pantaleo fullname: Pantaleo, Giuseppe – sequence: 10 givenname: Craig orcidid: 0000-0002-9435-0110 surname: Fenwick fullname: Fenwick, Craig – sequence: 11 givenname: Mireille orcidid: 0000-0001-7616-9775 surname: Centlivre fullname: Centlivre, Mireille – sequence: 12 givenname: Hugo orcidid: 0000-0002-4230-610X surname: Mouquet fullname: Mouquet, Hugo – sequence: 13 givenname: Sylvain surname: Cardinaud fullname: Cardinaud, Sylvain – sequence: 14 givenname: Sandra M. surname: Zurawski fullname: Zurawski, Sandra M. – sequence: 15 givenname: Gerard surname: Zurawski fullname: Zurawski, Gerard – sequence: 16 givenname: Pierre surname: Milpied fullname: Milpied, Pierre – sequence: 17 givenname: Lishan orcidid: 0000-0002-0350-5560 surname: Su fullname: Su, Lishan – sequence: 18 givenname: Yves surname: Lévy fullname: Lévy, Yves |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33253297$$D View this record in MEDLINE/PubMed https://hal.science/hal-04296375$$DView record in HAL |
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| ContentType | Journal Article |
| Copyright | COPYRIGHT 2020 Public Library of Science 2020 Godot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Attribution 2020 Godot et al 2020 Godot et al |
| Copyright_xml | – notice: COPYRIGHT 2020 Public Library of Science – notice: 2020 Godot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: Attribution – notice: 2020 Godot et al 2020 Godot et al |
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| DOI | 10.1371/journal.ppat.1009025 |
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| Keywords | Spleen HIV-1 Viral vaccines Recombinant vaccines Antibodies Vaccine development B cells HIV vaccines |
| Language | English |
| License | Attribution: http://creativecommons.org/licenses/by This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. cc-by Creative Commons Attribution License |
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| Notes | new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC7728200 I have read the journal's policy and the authors of this manuscript have the following competing interests: GZ, SZ, and YL are named inventors on CD40-targeting vaccine patents and patent filings held jointly by INSERM and the Baylor Research Institute. |
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| Snippet | The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In... Correlates of protection also included the generation of Env-specific T-cell responses and showed the importance of IgG isotype and ADCC (antibody-dependent... The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human Band T-cell responses in lymphoid organs. In... |
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| SubjectTerms | Agonists AIDS vaccines AIDS Vaccines - immunology Analysis Animals Antibodies Antibodies, Neutralizing - immunology Antibody-dependent cell-mediated cytotoxicity Antigen-presenting cells Antigens B cells B-Lymphocytes - immunology Biology and life sciences CD34 antigen CD40 antigen CD40 Antigens - immunology Composition CpG islands Cytotoxicity Dendritic cells env Gene Products, Human Immunodeficiency Virus - immunology Fetuses Flow cytometry Gag protein Hematopoietic Stem Cells Hepatocytes HIV HIV Antibodies - immunology HIV Infections - immunology HIV Infections - prevention & control HIV Infections - virology HIV-1 - immunology Human immunodeficiency virus Humans Identification and classification Immune system Immunization Immunodeficiency Immunoglobulin G Immunoglobulin G - immunology Immunoglobulins Immunological memory Life Sciences Lymphocytes Lymphocytes B Lymphocytes T Medicine and health sciences Memory cells Methods Mice Nef protein Pharmaceutical research Proteins Santé publique et épidémiologie Spleen T-Lymphocytes - immunology TLR9 TLR9 protein Toll-Like Receptor 9 - agonists Toll-like receptors Toxicity Vaccination Vaccines Viral envelopes Viruses |
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| Title | TLR-9 agonist and CD40-targeting vaccination induces HIV-1 envelope-specific B cells with a diversified immunoglobulin repertoire in humanized mice |
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