Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents

Berislav Bošnjak; Ivan Odak; Joana Barros-Martins; Inga Sandrock; Swantje I. Hammerschmidt; Marc Permanyer; Gwendolyn E. Patzer; Hristo Greorgiev; Rodrigo Gutierrez Jauregui; Alina Tscherne; Jan Hendrik Schwarz; Georgia Kalodimou; George Ssebyatika; Malgorzata Ciurkiewicz; Stefanie Willenzon; Anja Bubke; Jasmin Ristenpart; Christiane Ritter; Tamara Tuchel; Christian Meyer zu Natrup; Dai Lun Shin; Sabrina Clever; Leonard Limpinsel; Wolfgang Baumgärtner; Thomas Krey; Asisa Volz; Gerd Sutter; Reinhold Förster

doi:10.3389/fimmu.2021.772240

Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents

Berislav Bošnjak^*, Ivan Odak, Joana Barros-Martins, Inga Sandrock, Swantje I. Hammerschmidt, Marc Permanyer, Gwendolyn E. Patzer, Hristo Greorgiev, Rodrigo Gutierrez Jauregui, Alina Tscherne, Jan Hendrik Schwarz, Georgia Kalodimou, George Ssebyatika, Malgorzata Ciurkiewicz, Stefanie Willenzon, Anja Bubke, Jasmin Ristenpart, Christiane Ritter, Tamara Tuchel, Christian Meyer zu NatrupDai Lun Shin, Sabrina Clever, Leonard Limpinsel, Wolfgang Baumgärtner, Thomas Krey, Asisa Volz, Gerd Sutter, Reinhold Förster

^*Corresponding author for this work

Institute of Biochemistry

45 Citations (Scopus)

Abstract

Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8⁺ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8⁺ T cells and the development of Th1 - but not Th2 - CD4⁺ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections.

Original language	English
Article number	772240
Journal	Frontiers in Immunology
Volume	12
ISSN	1664-3224
DOIs	https://doi.org/10.3389/fimmu.2021.772240
Publication status	Published - 11.11.2021

Funding

This work was supported by Deutsche Forschungsgemeinschaft, (DFG, German research Foundation) Excellence Strategy EXC 2155 ?RESIST? to RF and TK (Project ID39087428); by funds of the state of Lower Saxony (14-76103-184 CORONA-11/20) to RF and TK; by funds of the BMBF ("NaFoUniMedCovid19? FKZ: 01KX2021; Projects ?COVIM?and ?B-FAST?) to RF and TK and Deutsche Forschungsgemeinschaft, Projektnummer 158989968 - SFB 900 (Projects B1 to RF and B10 to TK); Projektnumber Fo 334/7-1 and the Bundesministerium f?r Bildung und Forschung (DZIF 01.92100 and 01KX2026 to GSu, ZOOVAC 01KI1718 and RAPID 01KI1723G to AV) and by a BMBF (Federal Ministry of Education and Research) project entitled RAPID (Risk assessment in re-pandemic respiratory infectious diseases), 01KI1723G and by the Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20) to WB. This work was supported by Deutsche Forschungsgemeinschaft, (DFG, German research Foundation) Excellence Strategy EXC 2155 “RESIST” to RF and TK (Project ID39087428); by funds of the state of Lower Saxony (14-76103-184 CORONA-11/20) to RF and TK; by funds of the BMBF ("NaFoUniMedCovid19” FKZ: 01KX2021; Projects “COVIM”and “B-FAST”) to RF and TK and Deutsche Forschungsgemeinschaft, Projektnummer

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fimmu.2021.772240

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Bošnjak, B., Odak, I., Barros-Martins, J., Sandrock, I., Hammerschmidt, S. I., Permanyer, M., Patzer, G. E., Greorgiev, H., Gutierrez Jauregui, R., Tscherne, A., Schwarz, J. H., Kalodimou, G., Ssebyatika, G., Ciurkiewicz, M., Willenzon, S., Bubke, A., Ristenpart, J., Ritter, C., Tuchel, T., ... Förster, R. (2021). Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents. Frontiers in Immunology, 12, Article 772240. https://doi.org/10.3389/fimmu.2021.772240

@article{88d1360f9e694bcfb587f2995ca5d312,

title = "Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents",

abstract = "Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8+ T cells and the development of Th1 - but not Th2 - CD4+ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections.",

author = "Berislav Bo{\v s}njak and Ivan Odak and Joana Barros-Martins and Inga Sandrock and Hammerschmidt, \{Swantje I.\} and Marc Permanyer and Patzer, \{Gwendolyn E.\} and Hristo Greorgiev and \{Gutierrez Jauregui\}, Rodrigo and Alina Tscherne and Schwarz, \{Jan Hendrik\} and Georgia Kalodimou and George Ssebyatika and Malgorzata Ciurkiewicz and Stefanie Willenzon and Anja Bubke and Jasmin Ristenpart and Christiane Ritter and Tamara Tuchel and \{Meyer zu Natrup\}, Christian and Shin, \{Dai Lun\} and Sabrina Clever and Leonard Limpinsel and Wolfgang Baumg{\"a}rtner and Thomas Krey and Asisa Volz and Gerd Sutter and Reinhold F{\"o}rster",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 Bo{\v s}njak, Odak, Barros-Martins, Sandrock, Hammerschmidt, Permanyer, Patzer, Greorgiev, Gutierrez Jauregui, Tscherne, Schwarz, Kalodimou, Ssebyatika, Ciurkiewicz, Willenzon, Bubke, Ristenpart, Ritter, Tuchel, Meyer zu Natrup, Shin, Clever, Limpinsel, Baumg{\"a}rtner, Krey, Volz, Sutter and F{\"o}rster.",

year = "2021",

month = nov,

day = "11",

doi = "10.3389/fimmu.2021.772240",

language = "English",

volume = "12",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media",

}

Bošnjak, B, Odak, I, Barros-Martins, J, Sandrock, I, Hammerschmidt, SI, Permanyer, M, Patzer, GE, Greorgiev, H, Gutierrez Jauregui, R, Tscherne, A, Schwarz, JH, Kalodimou, G, Ssebyatika, G, Ciurkiewicz, M, Willenzon, S, Bubke, A, Ristenpart, J, Ritter, C, Tuchel, T, Meyer zu Natrup, C, Shin, DL, Clever, S, Limpinsel, L, Baumgärtner, W, Krey, T, Volz, A, Sutter, G & Förster, R 2021, 'Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents', Frontiers in Immunology, vol. 12, 772240. https://doi.org/10.3389/fimmu.2021.772240

TY - JOUR

T1 - Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents

AU - Bošnjak, Berislav

AU - Odak, Ivan

AU - Barros-Martins, Joana

AU - Sandrock, Inga

AU - Hammerschmidt, Swantje I.

AU - Permanyer, Marc

AU - Patzer, Gwendolyn E.

AU - Greorgiev, Hristo

AU - Gutierrez Jauregui, Rodrigo

AU - Tscherne, Alina

AU - Schwarz, Jan Hendrik

AU - Kalodimou, Georgia

AU - Ssebyatika, George

AU - Ciurkiewicz, Malgorzata

AU - Willenzon, Stefanie

AU - Bubke, Anja

AU - Ristenpart, Jasmin

AU - Ritter, Christiane

AU - Tuchel, Tamara

AU - Meyer zu Natrup, Christian

AU - Shin, Dai Lun

AU - Clever, Sabrina

AU - Limpinsel, Leonard

AU - Baumgärtner, Wolfgang

AU - Krey, Thomas

AU - Volz, Asisa

AU - Sutter, Gerd

AU - Förster, Reinhold

N1 - Publisher Copyright: Copyright © 2021 Bošnjak, Odak, Barros-Martins, Sandrock, Hammerschmidt, Permanyer, Patzer, Greorgiev, Gutierrez Jauregui, Tscherne, Schwarz, Kalodimou, Ssebyatika, Ciurkiewicz, Willenzon, Bubke, Ristenpart, Ritter, Tuchel, Meyer zu Natrup, Shin, Clever, Limpinsel, Baumgärtner, Krey, Volz, Sutter and Förster.

PY - 2021/11/11

Y1 - 2021/11/11

N2 - Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8+ T cells and the development of Th1 - but not Th2 - CD4+ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections.

AB - Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8+ T cells and the development of Th1 - but not Th2 - CD4+ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections.

UR - https://www.scopus.com/pages/publications/85120420353

U2 - 10.3389/fimmu.2021.772240

DO - 10.3389/fimmu.2021.772240

M3 - Journal articles

C2 - 34858430

AN - SCOPUS:85120420353

SN - 1664-3224

VL - 12

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 772240

ER -

Intranasal Delivery of MVA Vector Vaccine Induces Effective Pulmonary Immunity Against SARS-CoV-2 in Rodents

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