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Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization

Author

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  • Dennis Lapuente

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Jana Fuchs

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Jonas Willar

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Ana Vieira Antão

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Valentina Eberlein

    (Fraunhofer Institute for Cell Therapy and Immunology, IZI
    Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD)

  • Nadja Uhlig

    (Fraunhofer Institute for Cell Therapy and Immunology, IZI
    Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD)

  • Leila Issmail

    (Fraunhofer Institute for Cell Therapy and Immunology, IZI
    Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD)

  • Anna Schmidt

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Friederike Oltmanns

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Antonia Sophia Peter

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Sandra Mueller-Schmucker

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Pascal Irrgang

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Kirsten Fraedrich

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Andrea Cara

    (Istituto Superiore di Sanità)

  • Markus Hoffmann

    (German Primate Center-Leibniz Institute for Primate Research
    Georg-August-University Göttingen)

  • Stefan Pöhlmann

    (German Primate Center-Leibniz Institute for Primate Research
    Georg-August-University Göttingen)

  • Armin Ensser

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Cordula Pertl

    (Sirion Biotech)

  • Torsten Willert

    (Sirion Biotech)

  • Christian Thirion

    (Sirion Biotech)

  • Thomas Grunwald

    (Fraunhofer Institute for Cell Therapy and Immunology, IZI
    Fraunhofer Cluster of Excellence Immune-mediated Diseases CIMD)

  • Klaus Überla

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

  • Matthias Tenbusch

    (University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg)

Abstract

Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic plasmid DNA or mRNA priming result in systemic and mucosal immunity in mice. In contrast to two intramuscular applications of an mRNA vaccine, intranasal boosts with adenoviral vectors induce high levels of mucosal IgA and lung-resident memory T cells (TRM); mucosal neutralization of virus variants of concern is also enhanced. The mRNA prime provokes a comprehensive T cell response consisting of circulating and lung TRM after the boost, while the plasmid DNA prime induces mostly mucosal T cells. Concomitantly, the intranasal boost strategies lead to complete protection against a SARS-CoV-2 infection in mice. Our data thus suggest that mucosal booster immunizations after mRNA priming is a promising approach to establish mucosal immunity in addition to systemic responses.

Suggested Citation

  • Dennis Lapuente & Jana Fuchs & Jonas Willar & Ana Vieira Antão & Valentina Eberlein & Nadja Uhlig & Leila Issmail & Anna Schmidt & Friederike Oltmanns & Antonia Sophia Peter & Sandra Mueller-Schmucker, 2021. "Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27063-4
    DOI: 10.1038/s41467-021-27063-4
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    1. Elena Mitsi & Mariana O. Diniz & Jesús Reiné & Andrea M. Collins & Ryan E. Robinson & Angela Hyder-Wright & Madlen Farrar & Konstantinos Liatsikos & Josh Hamilton & Onyia Onyema & Britta C. Urban & Ca, 2023. "Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Anneliese S. Ashhurst & Matt D. Johansen & Joshua W. C. Maxwell & Skye Stockdale & Caroline L. Ashley & Anupriya Aggarwal & Rezwan Siddiquee & Stefan Miemczyk & Duc H. Nguyen & Joel P. Mackay & Claudi, 2022. "Mucosal TLR2-activating protein-based vaccination induces potent pulmonary immunity and protection against SARS-CoV-2 in mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Hong Lei & Aqu Alu & Jingyun Yang & Xi He & Cai He & Wenyan Ren & Zimin Chen & Weiqi Hong & Li Chen & Xuemei He & Li Yang & Jiong Li & Zhenling Wang & Wei Wang & Yuquan Wei & Shuaiyao Lu & Guangwen Lu, 2023. "Cationic crosslinked carbon dots-adjuvanted intranasal vaccine induces protective immunity against Omicron-included SARS-CoV-2 variants," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Aloysious Ssemaganda & Huong Mai Nguyen & Faisal Nuhu & Naima Jahan & Catherine M. Card & Sandra Kiazyk & Giulia Severini & Yoav Keynan & Ruey-Chyi Su & Hezhao Ji & Bernard Abrenica & Paul J. McLaren , 2022. "Expansion of cytotoxic tissue-resident CD8+ T cells and CCR6+CD161+ CD4+ T cells in the nasal mucosa following mRNA COVID-19 vaccination," Nature Communications, Nature, vol. 13(1), pages 1-9, December.

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