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Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections
MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung i...
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| Published in: | Cell reports (Cambridge) 2022-01, Vol.38 (1), p.110184-110184, Article 110184 |
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| creator | Brandi, Paola Conejero, Laura Cueto, Francisco J Martínez-Cano, Sarai Dunphy, Gillian Gómez, Manuel J Relaño, Carlos Saz-Leal, Paula Enamorado, Michel Quintas, Ana Dopazo, Ana Amores-Iniesta, Joaquín Del Fresno, Carlos Nistal-Villán, Estanislao Ardavín, Carlos Nieto, Antonio Casanovas, Miguel Subiza, José Luis Sancho, David |
| description | MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity. |
| doi_str_mv | 10.1016/j.celrep.2021.110184 |
| format | article |
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However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.</description><identifier>ISSN: 2211-1247</identifier><identifier>EISSN: 2211-1247</identifier><identifier>DOI: 10.1016/j.celrep.2021.110184</identifier><identifier>PMID: 34986349</identifier><language>eng</language><publisher>United States: Cell Press</publisher><subject>Administration, Intranasal ; Animals ; Antibodies, Viral - immunology ; Bacteria - immunology ; Bacterial Vaccines - administration & dosage ; Bacterial Vaccines - immunology ; Candidiasis - prevention & control ; Cell Line ; Chlorocebus aethiops ; Cytokines - biosynthesis ; Humans ; Immunity, Mucosal - immunology ; Influenza A virus - immunology ; L Cells ; Lung - immunology ; Metformin - pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes - immunology ; Orthomyxoviridae Infections - immunology ; Orthomyxoviridae Infections - prevention & control ; Orthomyxoviridae Infections - virology ; Respiratory Mucosa - immunology ; Respiratory Tract Infections - microbiology ; Respiratory Tract Infections - prevention & control ; Respiratory Tract Infections - virology ; Vaccines, Inactivated - administration & dosage ; Vaccines, Inactivated - immunology</subject><ispartof>Cell reports (Cambridge), 2022-01, Vol.38 (1), p.110184-110184, Article 110184</ispartof><rights>Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2021 The Authors 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-1cec31065fa409de1214828801c80a9afe1761c52dff5ddf1d71840ebb8f30a83</citedby><cites>FETCH-LOGICAL-c474t-1cec31065fa409de1214828801c80a9afe1761c52dff5ddf1d71840ebb8f30a83</cites><orcidid>0000-0001-6515-9221 ; 0000-0002-4111-4835 ; 0000-0001-7748-454X ; 0000-0003-2890-3984 ; 0000-0002-6263-4709 ; 0000-0003-2330-3963 ; 0000-0003-1771-7254 ; 0000-0002-7457-9583 ; 0000-0003-0991-4565 ; 0000-0002-4910-1684 ; 0000-0003-3721-7580</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,786,790,891,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34986349$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brandi, Paola</creatorcontrib><creatorcontrib>Conejero, Laura</creatorcontrib><creatorcontrib>Cueto, Francisco J</creatorcontrib><creatorcontrib>Martínez-Cano, Sarai</creatorcontrib><creatorcontrib>Dunphy, Gillian</creatorcontrib><creatorcontrib>Gómez, Manuel J</creatorcontrib><creatorcontrib>Relaño, Carlos</creatorcontrib><creatorcontrib>Saz-Leal, Paula</creatorcontrib><creatorcontrib>Enamorado, Michel</creatorcontrib><creatorcontrib>Quintas, Ana</creatorcontrib><creatorcontrib>Dopazo, Ana</creatorcontrib><creatorcontrib>Amores-Iniesta, Joaquín</creatorcontrib><creatorcontrib>Del Fresno, Carlos</creatorcontrib><creatorcontrib>Nistal-Villán, Estanislao</creatorcontrib><creatorcontrib>Ardavín, Carlos</creatorcontrib><creatorcontrib>Nieto, Antonio</creatorcontrib><creatorcontrib>Casanovas, Miguel</creatorcontrib><creatorcontrib>Subiza, José Luis</creatorcontrib><creatorcontrib>Sancho, David</creatorcontrib><title>Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections</title><title>Cell reports (Cambridge)</title><addtitle>Cell Rep</addtitle><description>MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.</description><subject>Administration, Intranasal</subject><subject>Animals</subject><subject>Antibodies, Viral - immunology</subject><subject>Bacteria - immunology</subject><subject>Bacterial Vaccines - administration & dosage</subject><subject>Bacterial Vaccines - immunology</subject><subject>Candidiasis - prevention & control</subject><subject>Cell Line</subject><subject>Chlorocebus aethiops</subject><subject>Cytokines - biosynthesis</subject><subject>Humans</subject><subject>Immunity, Mucosal - immunology</subject><subject>Influenza A virus - immunology</subject><subject>L Cells</subject><subject>Lung - immunology</subject><subject>Metformin - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Monocytes - immunology</subject><subject>Orthomyxoviridae Infections - immunology</subject><subject>Orthomyxoviridae Infections - prevention & control</subject><subject>Orthomyxoviridae Infections - virology</subject><subject>Respiratory Mucosa - immunology</subject><subject>Respiratory Tract Infections - microbiology</subject><subject>Respiratory Tract Infections - prevention & control</subject><subject>Respiratory Tract Infections - virology</subject><subject>Vaccines, Inactivated - administration & dosage</subject><subject>Vaccines, Inactivated - immunology</subject><issn>2211-1247</issn><issn>2211-1247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNpVUcFOGzEQtaqiggJ_UFU-9pLg8Xp3nQtShVpAouqF9mo53jE4yq4X2xuRS7-dCaGI-jCeGb958-TH2GcQCxDQnK8XDjcJx4UUEhZAPa0-sBMpAeYgVfvxXX7MznJeCzqNAFiqT-y4UkvdUDhhf--SDQN2PPT9NISy42HoJldCHPhqx8sDUsNSvbWFUP3kYrYbvrXO0Rj_-QcqwccUC7qSub0nslw4Po2YQo9D2WNDopgwj5SUmPYrPL6syKfsyNtNxrPXe8Z-__h-d3k9v_11dXP57XbuVKvKHBy6CkRTe6vEskOQoLTUWoDTwi6tR2gbcLXsvK-7zkPX0ocIXK20r4TV1YxdHHjHadVj50gZiTIjibRpZ6IN5v-XITyY-7g1uq1rpSQRfH0lSPFxwlxMHzJ5sLEDxikb2UAr20o1LUHVAepSzDmhf1sDwuzdM2tzcM_s3TMH92jsy3uJb0P_vKqeAVX7nAs</recordid><startdate>20220104</startdate><enddate>20220104</enddate><creator>Brandi, Paola</creator><creator>Conejero, Laura</creator><creator>Cueto, Francisco J</creator><creator>Martínez-Cano, Sarai</creator><creator>Dunphy, Gillian</creator><creator>Gómez, Manuel J</creator><creator>Relaño, Carlos</creator><creator>Saz-Leal, Paula</creator><creator>Enamorado, Michel</creator><creator>Quintas, Ana</creator><creator>Dopazo, Ana</creator><creator>Amores-Iniesta, Joaquín</creator><creator>Del Fresno, Carlos</creator><creator>Nistal-Villán, Estanislao</creator><creator>Ardavín, Carlos</creator><creator>Nieto, Antonio</creator><creator>Casanovas, Miguel</creator><creator>Subiza, José Luis</creator><creator>Sancho, David</creator><general>Cell Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6515-9221</orcidid><orcidid>https://orcid.org/0000-0002-4111-4835</orcidid><orcidid>https://orcid.org/0000-0001-7748-454X</orcidid><orcidid>https://orcid.org/0000-0003-2890-3984</orcidid><orcidid>https://orcid.org/0000-0002-6263-4709</orcidid><orcidid>https://orcid.org/0000-0003-2330-3963</orcidid><orcidid>https://orcid.org/0000-0003-1771-7254</orcidid><orcidid>https://orcid.org/0000-0002-7457-9583</orcidid><orcidid>https://orcid.org/0000-0003-0991-4565</orcidid><orcidid>https://orcid.org/0000-0002-4910-1684</orcidid><orcidid>https://orcid.org/0000-0003-3721-7580</orcidid></search><sort><creationdate>20220104</creationdate><title>Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections</title><author>Brandi, Paola ; 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However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.</abstract><cop>United States</cop><pub>Cell Press</pub><pmid>34986349</pmid><doi>10.1016/j.celrep.2021.110184</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-6515-9221</orcidid><orcidid>https://orcid.org/0000-0002-4111-4835</orcidid><orcidid>https://orcid.org/0000-0001-7748-454X</orcidid><orcidid>https://orcid.org/0000-0003-2890-3984</orcidid><orcidid>https://orcid.org/0000-0002-6263-4709</orcidid><orcidid>https://orcid.org/0000-0003-2330-3963</orcidid><orcidid>https://orcid.org/0000-0003-1771-7254</orcidid><orcidid>https://orcid.org/0000-0002-7457-9583</orcidid><orcidid>https://orcid.org/0000-0003-0991-4565</orcidid><orcidid>https://orcid.org/0000-0002-4910-1684</orcidid><orcidid>https://orcid.org/0000-0003-3721-7580</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cell reports (Cambridge), 2022-01, Vol.38 (1), p.110184-110184, Article 110184 |
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| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS |
| subjects | Administration, Intranasal Animals Antibodies, Viral - immunology Bacteria - immunology Bacterial Vaccines - administration & dosage Bacterial Vaccines - immunology Candidiasis - prevention & control Cell Line Chlorocebus aethiops Cytokines - biosynthesis Humans Immunity, Mucosal - immunology Influenza A virus - immunology L Cells Lung - immunology Metformin - pharmacology Mice Mice, Inbred C57BL Mice, Knockout Monocytes - immunology Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - prevention & control Orthomyxoviridae Infections - virology Respiratory Mucosa - immunology Respiratory Tract Infections - microbiology Respiratory Tract Infections - prevention & control Respiratory Tract Infections - virology Vaccines, Inactivated - administration & dosage Vaccines, Inactivated - immunology |
| title | Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections |
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