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  1. Article ; Online: An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission.

    Adler, Julia M / Martin Vidal, Ricardo / Langner, Christine / Vladimirova, Daria / Abdelgawad, Azza / Kunecova, Daniela / Lin, Xiaoyuan / Nouailles, Geraldine / Voss, Anne / Kunder, Sandra / Gruber, Achim D / Wu, Haibo / Osterrieder, Nikolaus / Kunec, Dusan / Trimpert, Jakob

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 995

    Abstract: The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways-the ... ...

    Abstract The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways-the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission.
    MeSH term(s) Animals ; Cricetinae ; Male ; Humans ; COVID-19 Vaccines ; BNT162 Vaccine ; COVID-19/prevention & control ; mRNA Vaccines ; SARS-CoV-2 ; Mesocricetus ; Antibodies, Viral ; Antibodies, Neutralizing
    Chemical Substances COVID-19 Vaccines ; BNT162 Vaccine ; mRNA Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing
    Language English
    Publishing date 2024-02-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45348-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A non-transmissible live attenuated SARS-CoV-2 vaccine.

    Adler, Julia M / Martin Vidal, Ricardo / Voß, Anne / Kunder, Sandra / Nascimento, Mariana / Abdelgawad, Azza / Langner, Christine / Vladimirova, Daria / Osterrieder, Nikolaus / Gruber, Achim D / Kunec, Dusan / Trimpert, Jakob

    Molecular therapy : the journal of the American Society of Gene Therapy

    2023  Volume 31, Issue 8, Page(s) 2391–2407

    Abstract: Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Conceptionally, LAVs have several advantages, including presentation of the ... ...

    Abstract Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Conceptionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmission of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV is a promising strategy to increase vaccine safety and prevent vaccine transmission without compromising vaccine efficacy.
    MeSH term(s) Animals ; Cricetinae ; Humans ; COVID-19 Vaccines ; COVID-19/prevention & control ; Pandemics ; SARS-CoV-2 ; Vaccines, Attenuated ; Antibodies, Viral ; Antibodies, Neutralizing
    Chemical Substances COVID-19 Vaccines ; Vaccines, Attenuated ; Antibodies, Viral ; Antibodies, Neutralizing
    Language English
    Publishing date 2023-05-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2023.05.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Jg. 1995 - 2021: Lesesall (2.OG)
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  3. Article ; Online: Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters.

    Nouailles, Geraldine / Adler, Julia M / Pennitz, Peter / Peidli, Stefan / Teixeira Alves, Luiz Gustavo / Baumgardt, Morris / Bushe, Judith / Voss, Anne / Langenhagen, Alina / Langner, Christine / Martin Vidal, Ricardo / Pott, Fabian / Kazmierski, Julia / Ebenig, Aileen / Lange, Mona V / Mühlebach, Michael D / Goekeri, Cengiz / Simmons, Szandor / Xing, Na /
    Abdelgawad, Azza / Herwig, Susanne / Cichon, Günter / Niemeyer, Daniela / Drosten, Christian / Goffinet, Christine / Landthaler, Markus / Blüthgen, Nils / Wu, Haibo / Witzenrath, Martin / Gruber, Achim D / Praktiknjo, Samantha D / Osterrieder, Nikolaus / Wyler, Emanuel / Kunec, Dusan / Trimpert, Jakob

    Nature microbiology

    2023  Volume 8, Issue 5, Page(s) 860–874

    Abstract: Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune ...

    Abstract Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.
    MeSH term(s) Animals ; Cricetinae ; Humans ; Vaccines, Attenuated ; SARS-CoV-2 ; COVID-19/prevention & control ; COVID-19 Vaccines ; BNT162 Vaccine ; Pandemics ; Mesocricetus
    Chemical Substances sCPD9 COVID-19 vaccine ; Vaccines, Attenuated ; COVID-19 Vaccines ; BNT162 Vaccine
    Language English
    Publishing date 2023-04-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-023-01352-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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