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  1. Article ; Online: Infectious RNA vaccine protects mice against chikungunya virus infection.

    Szurgot, Inga / Ljungberg, Karl / Kümmerer, Beate M / Liljeström, Peter

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 21076

    Abstract: We describe a novel vaccine platform that can generate protective immunity to chikungunya virus (CHIKV) in C57BL/6J mice after a single immunization by employing an infectious RNA (iRNA), which upon introduction into a host cell launches an infectious ... ...

    Abstract We describe a novel vaccine platform that can generate protective immunity to chikungunya virus (CHIKV) in C57BL/6J mice after a single immunization by employing an infectious RNA (iRNA), which upon introduction into a host cell launches an infectious attenuated virus. We and others have previously reported that an engineered deletion of 183 nucleotides in the nsP3 gene attenuates chikungunya virus (CHIKV) and reduces in vivo viral replication and viremia after challenge in mice, macaques and man. Here, we demonstrated that in vitro transfection of iRNA carrying the nsP3 deletion generated infectious viruses, and after intramuscular injection, the iRNA induced robust antibody responses in mice. The iRNA was superior at eliciting binding and neutralizing antibody responses as compared to a DNA vaccine encoding the same RNA (iDNA) or a non-propagating RNA replicon (RREP) lacking the capsid encoding gene. Subsequent challenge with a high dose of CHIKV demonstrated that the antibody responses induced by this vaccine candidate protected animals from viremia. The iRNA approach constitutes a novel vaccine platform with the potential to impact the spread of CHIKV. Moreover, we believe that this approach is likely applicable also to other positive-strand viruses.
    MeSH term(s) Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Chikungunya Fever/immunology ; Chikungunya Fever/prevention & control ; Chikungunya Fever/virology ; Chikungunya virus/genetics ; Chikungunya virus/immunology ; Chikungunya virus/pathogenicity ; Female ; Immunogenicity, Vaccine ; Injections, Intramuscular ; Mice ; Mice, Inbred C57BL ; Mutation ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/genetics ; Vaccines, Attenuated/immunology ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/immunology ; mRNA Vaccines
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Vaccines, Attenuated ; Vaccines, Synthetic ; Viral Nonstructural Proteins
    Language English
    Publishing date 2020-12-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-78009-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice.

    Szurgot, Inga / Hanke, Leo / Sheward, Daniel J / Vidakovics, Laura Perez / Murrell, Ben / McInerney, Gerald M / Liljeström, Peter

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 3125

    Abstract: The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the ... ...

    Abstract The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding either SARS-CoV-2 spike glycoprotein (DREP-S) or a spike ectodomain trimer stabilized in prefusion conformation (DREP-S
    MeSH term(s) Animals ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; Female ; HEK293 Cells ; Humans ; Mice ; Mice, Inbred C57BL ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Vaccines, DNA/immunology
    Chemical Substances COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Vaccines, DNA ; spike glycoprotein, SARS-CoV
    Language English
    Publishing date 2021-02-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-82498-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: DNA-launched RNA replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice

    Inga Szurgot / Leo Hanke / Daniel J. Sheward / Laura Perez Vidakovics / Ben Murrell / Gerald M. McInerney / Peter Liljeström

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: Abstract The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and ... ...

    Abstract Abstract The outbreak of the SARS-CoV-2 virus and its rapid spread into a global pandemic made the urgent development of scalable vaccines to prevent coronavirus disease (COVID-19) a global health and economic imperative. Here, we characterized and compared the immunogenicity of two alphavirus-based DNA-launched self-replicating (DREP) vaccine candidates encoding either SARS-CoV-2 spike glycoprotein (DREP-S) or a spike ectodomain trimer stabilized in prefusion conformation (DREP-Secto). We observed that the two DREP constructs were immunogenic in mice inducing both binding and neutralizing antibodies as well as T cell responses. Interestingly, the DREP coding for the unmodified spike turned out to be more potent vaccine candidate, eliciting high titers of SARS-CoV-2 specific IgG antibodies that were able to efficiently neutralize pseudotyped virus after a single immunization. In addition, both DREP constructs were able to efficiently prime responses that could be boosted with a heterologous spike protein immunization. These data provide important novel insights into SARS-CoV-2 vaccine design using a rapid response DNA vaccine platform. Moreover, they encourage the use of mixed vaccine modalities as a strategy to combat SARS-CoV-2.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Virus-like particles as vaccine.

    Chroboczek, Jadwiga / Szurgot, Inga / Szolajska, Ewa

    Acta biochimica Polonica

    2014  Volume 61, Issue 3, Page(s) 531–539

    Abstract: This review presents data on commercial and experimental virus-like particle (VLP) vaccines, including description of VLP vaccines against influenza. Virus-like particles are multimeric, sometimes multiprotein nanostructures assembled from viral ... ...

    Abstract This review presents data on commercial and experimental virus-like particle (VLP) vaccines, including description of VLP vaccines against influenza. Virus-like particles are multimeric, sometimes multiprotein nanostructures assembled from viral structural proteins and are devoid of any genetic material. VLPs present repetitive high-density displays of viral surface proteins. Importantly, they contain functional viral proteins responsible for cell penetration by the virus, ensuring efficient cell entry and thus tissue-specific targeting, determined by the origin of the virus. The foremost application of VLPs is in vaccinology, where they provide delivery systems that combine good safety profiles with strong immunogenicity and constitute a safe alternative to inactivated infectious viruses. These stable and versatile nanoparticles display excellent adjuvant properties capable of inducing innate and cognate immune responses. They present both, high-density B-cell epitopes, for antibody production and intracellular T-cell epitopes, thus inducing, respectively, potent humoral and cellular immune responses. Uptake of VLPs by antigen-presenting cells leads to efficient immune responses resulting in control of pathogenic microorganisms.
    MeSH term(s) Epitopes, B-Lymphocyte/immunology ; Epitopes, T-Lymphocyte/immunology ; Humans ; Influenza A virus/genetics ; Influenza A virus/immunology ; Influenza A virus/ultrastructure ; Influenza, Human/prevention & control ; Nanostructures ; Vaccination ; Vaccines, Virus-Like Particle/immunology
    Chemical Substances Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte ; Vaccines, Virus-Like Particle
    Language English
    Publishing date 2014
    Publishing country Poland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 595762-x
    ISSN 1734-154X ; 0001-527X
    ISSN (online) 1734-154X
    ISSN 0001-527X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Leukocytes and drug-resistant cancer cells are targets for intracellular delivery by adenoviral dodecahedron.

    Jedynak, Marta / Laurin, David / Dolega, Patryk / Podsiadla-Bialoskorska, Malgorzata / Szurgot, Inga / Chroboczek, Jadwiga / Szolajska, Ewa

    Nanomedicine : nanotechnology, biology, and medicine

    2018  Volume 14, Issue 6, Page(s) 1853–1865

    Abstract: One of the major factors limiting the effectiveness of cancer chemotherapy is inefficient drug delivery. Systems enabling efficient delivery and enhanced intracellular uptake appear particularly promising in this respect. Virus-like particle, adenoviral ... ...

    Abstract One of the major factors limiting the effectiveness of cancer chemotherapy is inefficient drug delivery. Systems enabling efficient delivery and enhanced intracellular uptake appear particularly promising in this respect. Virus-like particle, adenoviral dodecahedron (Dd), employs receptor-mediated endocytosis for cell penetration and is able to deliver intracellularly dozens of cargo molecules attached to one particle. We focused on studying Dd properties in the context of cancer treatment, showing that intratumoral injection of Dd, assessed in mouse xenograft model, results in vector accumulation in tumor without spreading in off-target organs. Moreover, we demonstrated that Dd is a promising vector targeting leukocytes and drug-resistant cancer cells. Dd uptake by human blood cells analyzed in vitro indicated the preference for leukocytes in comparison to red blood cells and platelets. Furthermore, internalization of Dd-doxorubicin conjugate by drug-resistant cells leads to increased nuclear accumulation of doxorubicin and significant enhancement of cytotoxicity against target cancer cells.
    MeSH term(s) Adenoviridae/genetics ; Animals ; Antibiotics, Antineoplastic/pharmacology ; Capsid Proteins/administration & dosage ; Capsid Proteins/genetics ; Cells, Cultured ; Doxorubicin/pharmacology ; Drug Delivery Systems ; Drug Resistance, Neoplasm ; Humans ; Leukocytes/cytology ; Leukocytes/metabolism ; Mice ; Neoplasms/therapy
    Chemical Substances Antibiotics, Antineoplastic ; Capsid Proteins ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2018-05-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2183417-9
    ISSN 1549-9642 ; 1549-9634
    ISSN (online) 1549-9642
    ISSN 1549-9634
    DOI 10.1016/j.nano.2018.05.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity.

    Falck-Jones, Sara / Vangeti, Sindhu / Yu, Meng / Falck-Jones, Ryan / Cagigi, Alberto / Badolati, Isabella / Österberg, Björn / Lautenbach, Maximilian Julius / Åhlberg, Eric / Lin, Ang / Lepzien, Rico / Szurgot, Inga / Lenart, Klara / Hellgren, Fredrika / Maecker, Holden / Sälde, Jörgen / Albert, Jan / Johansson, Niclas / Bell, Max /
    Loré, Karin / Färnert, Anna / Smed-Sörensen, Anna

    The Journal of clinical investigation

    2021  Volume 131, Issue 6

    Abstract: The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but ... ...

    Abstract The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied the blood and airways of patients with COVID-19 across disease severities at multiple time points. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of patients with COVID-19 compared with healthy controls. M-MDSCs isolated from patients with COVID-19 suppressed T cell proliferation and IFN-γ production partly via an arginase 1-dependent (Arg-1-dependent) mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. Patients with COVID-19 had fewer T cells and downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expanded in the blood of patients with COVID-19, suppressed T cells, and were strongly associated with disease severity, indicating a role for M-MDSCs in the dysregulated COVID-19 immune response.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Arginase/blood ; COVID-19/blood ; COVID-19/immunology ; COVID-19/pathology ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Influenza, Human/blood ; Influenza, Human/immunology ; Influenza, Human/pathology ; Interferon-gamma/blood ; Interleukin-6/blood ; Leukocyte Count ; Male ; Middle Aged ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/pathology ; Pandemics ; Respiratory System/immunology ; Respiratory System/pathology ; SARS-CoV-2 ; Severity of Illness Index ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology ; Young Adult
    Chemical Substances IL6 protein, human ; Interleukin-6 ; Interferon-gamma (82115-62-6) ; ARG1 protein, human (EC 3.5.3.1) ; Arginase (EC 3.5.3.1)
    Language English
    Publishing date 2021-01-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI144734
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Self-adjuvanting influenza candidate vaccine presenting epitopes for cell-mediated immunity on a proteinaceous multivalent nanoplatform

    Szurgot, Inga / Benedicte Lambrecht / David Laurin / Ewa Szolajska / Guy Schoehn / Jadwiga Chroboczek / Laurence Chaperot

    Vaccine. 2013 Sept. 13, v. 31, no. 40

    2013  

    Abstract: We exploit the features of a virus-like particle, adenoviral dodecahedron (Ad Dd), for engineering a multivalent vaccination platform carrying influenza epitopes for cell-mediated immunity. The delivery platform, Ad Dd, is a proteinaceous, polyvalent, ... ...

    Abstract We exploit the features of a virus-like particle, adenoviral dodecahedron (Ad Dd), for engineering a multivalent vaccination platform carrying influenza epitopes for cell-mediated immunity. The delivery platform, Ad Dd, is a proteinaceous, polyvalent, and biodegradable nanoparticle endowed with remarkable endocytosis activity that can be engineered to carry 60 copies of a peptide. Influenza M1 is the most abundant influenza internal protein with the conserved primary structure. Two different M1 immunodominant epitopes were separately inserted in Dd external positions without destroying the particles’ dodecahedric structure. Both kinds of DdFluM1 obtained through expression in baculovirus system were properly presented by human dendritic cells triggering efficient activation of antigen-specific T cells responses. Importantly, the candidate vaccine was able to induce cellular immunity in vivo in chickens. These results warrant further investigation of Dd as a platform for candidate vaccine, able to stimulate cellular immune responses.
    Keywords biodegradability ; cell-mediated immunity ; chickens ; dendritic cells ; endocytosis ; engineering ; humans ; immunodominant epitopes ; influenza ; nanoparticles ; T-lymphocytes ; vaccination ; vaccines
    Language English
    Dates of publication 2013-0913
    Size p. 4338-4346.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2013.07.021
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Self-adjuvanting influenza candidate vaccine presenting epitopes for cell-mediated immunity on a proteinaceous multivalent nanoplatform.

    Szurgot, Inga / Szolajska, Ewa / Laurin, David / Lambrecht, Benedicte / Chaperot, Laurence / Schoehn, Guy / Chroboczek, Jadwiga

    Vaccine

    2013  Volume 31, Issue 40, Page(s) 4338–4346

    Abstract: We exploit the features of a virus-like particle, adenoviral dodecahedron (Ad Dd), for engineering a multivalent vaccination platform carrying influenza epitopes for cell-mediated immunity. The delivery platform, Ad Dd, is a proteinaceous, polyvalent, ... ...

    Abstract We exploit the features of a virus-like particle, adenoviral dodecahedron (Ad Dd), for engineering a multivalent vaccination platform carrying influenza epitopes for cell-mediated immunity. The delivery platform, Ad Dd, is a proteinaceous, polyvalent, and biodegradable nanoparticle endowed with remarkable endocytosis activity that can be engineered to carry 60 copies of a peptide. Influenza M1 is the most abundant influenza internal protein with the conserved primary structure. Two different M1 immunodominant epitopes were separately inserted in Dd external positions without destroying the particles' dodecahedric structure. Both kinds of DdFluM1 obtained through expression in baculovirus system were properly presented by human dendritic cells triggering efficient activation of antigen-specific T cells responses. Importantly, the candidate vaccine was able to induce cellular immunity in vivo in chickens. These results warrant further investigation of Dd as a platform for candidate vaccine, able to stimulate cellular immune responses.
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Chickens ; Dendritic Cells/immunology ; Endocytosis/immunology ; Epitopes/immunology ; Humans ; Immunity, Cellular ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Interferon-gamma/biosynthesis ; Lymphocyte Activation/immunology ; Nanoparticles/metabolism ; Orthomyxoviridae Infections/immunology ; Vaccination ; Viral Matrix Proteins/immunology
    Chemical Substances Epitopes ; Influenza Vaccines ; M1 protein, Influenza A virus ; Viral Matrix Proteins ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2013-09-13
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2013.07.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: DNA-launched RNA replicon vaccines induce potent anti-Ebolavirus immune responses that can be further improved by a recombinant MVA boost.

    Öhlund, Pontus / García-Arriaza, Juan / Zusinaite, Eva / Szurgot, Inga / Männik, Andres / Kraus, Annette / Ustav, Mart / Merits, Andres / Esteban, Mariano / Liljeström, Peter / Ljungberg, Karl

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 12459

    Abstract: There are currently no licensed therapeutic treatment or preventive vaccines against Ebolavirus disease, and the 2013-2016 West African outbreak of Ebolavirus disease spread rapidly and resulted in almost 30,000 cases and more than 11,000 deaths. However, ...

    Abstract There are currently no licensed therapeutic treatment or preventive vaccines against Ebolavirus disease, and the 2013-2016 West African outbreak of Ebolavirus disease spread rapidly and resulted in almost 30,000 cases and more than 11,000 deaths. However, the devastating outbreak has spurred the development of novel Ebolavirus vaccines. Here, we demonstrate that alphavirus-based DNA-launched self-replicating RNA replicon vaccines (DREP) encoding either the glycoprotein (GP) gene or co-expressing the GP and VP40 genes of Sudan or Zaire Ebolavirus are immunogenic in mice inducing both binding and neutralizing antibodies as well as CD8 T cell responses. In addition, antibodies were cross-reactive against another Ebolavirus, although the specificity was higher for the vaccination antigen. DREP vaccines were more immunogenic than recombinant MVA vaccines expressing the same Ebolavirus antigens. However, a DREP prime followed by an MVA boost immunization regimen improved vaccine immunogenicity as compared to DREP and MVA homologous prime-boost immunizations. Moreover, we show that a bivalent approach targeting both Sudan and Zaire Ebolavirus can be employed without significant loss of immunity. This opens for further investigation of a pan-Ebolavirus or even a pan-filovirus vaccine.
    MeSH term(s) Alphavirus/immunology ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Chlorocebus aethiops ; DNA/immunology ; Ebola Vaccines/immunology ; Ebolavirus/immunology ; Female ; Glycoproteins/immunology ; Humans ; Immunization, Secondary/methods ; Mice ; Mice, Inbred BALB C ; RNA/immunology ; Replicon/immunology ; Sudan ; Vaccination/methods ; Vaccines, DNA/immunology ; Vero Cells ; Viral Vaccines/immunology
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Ebola Vaccines ; Glycoproteins ; MVA vaccine ; Vaccines, DNA ; Viral Vaccines ; RNA (63231-63-0) ; DNA (9007-49-2)
    Language English
    Publishing date 2018-08-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-31003-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques.

    Marlin, Romain / Godot, Veronique / Cardinaud, Sylvain / Galhaut, Mathilde / Coleon, Severin / Zurawski, Sandra / Dereuddre-Bosquet, Nathalie / Cavarelli, Mariangela / Gallouët, Anne-Sophie / Maisonnasse, Pauline / Dupaty, Léa / Fenwick, Craig / Naninck, Thibaut / Lemaitre, Julien / Gomez-Pacheco, Mario / Kahlaoui, Nidhal / Contreras, Vanessa / Relouzat, Francis / Fang, Raphaël Ho Tsong /
    Wang, Zhiqing / Ellis, Jerome / Chapon, Catherine / Centlivre, Mireille / Wiedemann, Aurelie / Lacabaratz, Christine / Surenaud, Mathieu / Szurgot, Inga / Liljeström, Peter / Planas, Delphine / Bruel, Timothée / Schwartz, Olivier / Werf, Sylvie van der / Pantaleo, Giuseppe / Prague, Mélanie / Thiébaut, Rodolphe / Zurawski, Gerard / Lévy, Yves / Grand, Roger Le

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 5215

    Abstract: Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children ...

    Abstract Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. Additionally, we demonstrate that a single dose of the αCD40.RBD vaccine, injected without adjuvant, is sufficient to boost a rapid increase in neutralizing antibodies in convalescent non-human primates (NHPs) exposed six months previously to SARS-CoV-2. Vaccine-elicited antibodies cross-neutralize different SARS-CoV-2 variants, including D614G, B1.1.7 and to a lesser extent B1.351. Such vaccination significantly improves protection against a new high-dose virulent challenge versus that in non-vaccinated convalescent animals.
    MeSH term(s) Animals ; Antigen-Presenting Cells/immunology ; B-Lymphocytes/immunology ; CD40 Antigens/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; Convalescence ; Humans ; Macaca ; Mice ; Mutation ; Protein Domains ; Reinfection/prevention & control ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; T-Lymphocytes/immunology ; Vaccination ; Vaccines, Subunit/immunology
    Chemical Substances CD40 Antigens ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Vaccines, Subunit ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-09-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-25382-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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