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

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, Pascal Irrgang, Kirsten Fraedrich, Andrea Cara, Markus Hoffmann, Stefan Pöhlmann, Armin Ensser, Cordula Pertl, Torsten Willert, Christian Thirion, Thomas Grunwald, Klaus Überla and Matthias Tenbusch ()
Additional contact information
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
Nadja Uhlig: Fraunhofer Institute for Cell Therapy and Immunology, IZI
Leila Issmail: Fraunhofer Institute for Cell Therapy and Immunology, IZI
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
Stefan Pöhlmann: German Primate Center-Leibniz Institute for Primate Research
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
Klaus Überla: University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg
Matthias Tenbusch: University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-27063-4

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