Strategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infec...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2024-03, Vol.121 (10), p.e2313681121-e2313681121 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Chang, Soojeong Shin, Kwang-Soo Park, Bongju Park, Seowoo Shin, Jieun Park, Hyemin Jung, In Kyung Kim, Jong Heon Bae, Seong Eun Kim, Jae-Ouk Baek, Seung Ho Kim, Green Hong, Jung Joo Seo, Hyungseok Volz, Erik Kang, Chang-Yuil |
| description | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants. We developed bivalent vaccine AdCLD-CoV19-1 BA.5/BA.2.75 and trivalent vaccines AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 and AdCLD-CoV19-1 XBB.1.5/BN.1/BQ.1.1 using an Ad5/35 platform-based non-replicating recombinant adenoviral vector. We compared immune responses elicited by the monovalent and multivalent vaccines in mice and macaques. We found that the BA.5/BA.2.75 bivalent and the XBB/BN.1/BQ.1.1 and XBB.1.5/BN.1/BQ.1.1 trivalent vaccines exhibited improved cross-neutralization ability compared to their respective monovalent vaccines. These data suggest that the developed multivalent vaccines enhance immunity against circulating Omicron subvariants and effectively elicit neutralizing antibodies across a broad spectrum of SARS-CoV-2 variants. |
| doi_str_mv | 10.1073/pnas.2313681121 |
| format | Article |
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These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants. We developed bivalent vaccine AdCLD-CoV19-1 BA.5/BA.2.75 and trivalent vaccines AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 and AdCLD-CoV19-1 XBB.1.5/BN.1/BQ.1.1 using an Ad5/35 platform-based non-replicating recombinant adenoviral vector. We compared immune responses elicited by the monovalent and multivalent vaccines in mice and macaques. We found that the BA.5/BA.2.75 bivalent and the XBB/BN.1/BQ.1.1 and XBB.1.5/BN.1/BQ.1.1 trivalent vaccines exhibited improved cross-neutralization ability compared to their respective monovalent vaccines. These data suggest that the developed multivalent vaccines enhance immunity against circulating Omicron subvariants and effectively elicit neutralizing antibodies across a broad spectrum of SARS-CoV-2 variants.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2313681121</identifier><identifier>PMID: 38408238</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Antibodies ; Antibodies, Neutralizing ; Antibodies, Viral ; Biological Sciences ; Coronaviruses ; COVID-19 ; COVID-19 - prevention & control ; COVID-19 vaccines ; COVID-19 Vaccines - genetics ; Humans ; Immune response ; Macaca ; Mice ; Neutralization ; SARS-CoV-2 - genetics ; Severe acute respiratory syndrome coronavirus 2 ; Vaccines ; Vaccines, Combined ; Viral diseases</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2024-03, Vol.121 (10), p.e2313681121-e2313681121</ispartof><rights>Copyright National Academy of Sciences Mar 5, 2024</rights><rights>Copyright © 2024 the Author(s). Published by PNAS. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c376t-1198909c3ef2a9664fa83329a590b1bde1bdd7dfc71e0a628dacf1a1744c383b3</cites><orcidid>0000-0001-7020-2140 ; 0009-0007-5351-3722 ; 0000-0002-1843-6967 ; 0000-0001-8062-470X ; 0009-0002-7055-1417 ; 0000-0003-3294-6936 ; 0009-0006-5244-4270 ; 0009-0004-0819-3529 ; 0000-0001-6268-8937 ; 0000-0002-1961-6687 ; 0000-0001-7897-4540</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10927586/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10927586/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38408238$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Soojeong</creatorcontrib><creatorcontrib>Shin, Kwang-Soo</creatorcontrib><creatorcontrib>Park, Bongju</creatorcontrib><creatorcontrib>Park, Seowoo</creatorcontrib><creatorcontrib>Shin, Jieun</creatorcontrib><creatorcontrib>Park, Hyemin</creatorcontrib><creatorcontrib>Jung, In Kyung</creatorcontrib><creatorcontrib>Kim, Jong Heon</creatorcontrib><creatorcontrib>Bae, Seong Eun</creatorcontrib><creatorcontrib>Kim, Jae-Ouk</creatorcontrib><creatorcontrib>Baek, Seung Ho</creatorcontrib><creatorcontrib>Kim, Green</creatorcontrib><creatorcontrib>Hong, Jung Joo</creatorcontrib><creatorcontrib>Seo, Hyungseok</creatorcontrib><creatorcontrib>Volz, Erik</creatorcontrib><creatorcontrib>Kang, Chang-Yuil</creatorcontrib><title>Strategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants. We developed bivalent vaccine AdCLD-CoV19-1 BA.5/BA.2.75 and trivalent vaccines AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 and AdCLD-CoV19-1 XBB.1.5/BN.1/BQ.1.1 using an Ad5/35 platform-based non-replicating recombinant adenoviral vector. We compared immune responses elicited by the monovalent and multivalent vaccines in mice and macaques. We found that the BA.5/BA.2.75 bivalent and the XBB/BN.1/BQ.1.1 and XBB.1.5/BN.1/BQ.1.1 trivalent vaccines exhibited improved cross-neutralization ability compared to their respective monovalent vaccines. These data suggest that the developed multivalent vaccines enhance immunity against circulating Omicron subvariants and effectively elicit neutralizing antibodies across a broad spectrum of SARS-CoV-2 variants.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Neutralizing</subject><subject>Antibodies, Viral</subject><subject>Biological Sciences</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 vaccines</subject><subject>COVID-19 Vaccines - genetics</subject><subject>Humans</subject><subject>Immune response</subject><subject>Macaca</subject><subject>Mice</subject><subject>Neutralization</subject><subject>SARS-CoV-2 - genetics</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Vaccines</subject><subject>Vaccines, Combined</subject><subject>Viral diseases</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkUtv1TAQhS0EopfCmh2yxIZNev1KYq9QdQulUqUueGytiTMJqZI42E6k--9x1dICi9Es5pujOXMIecvZGWe13C8zxDMhuaw054I_IzvODC8qZdhzsmNM1IVWQp2QVzHeMsZMqdlLciK1YlpIvSPb1xQgYX-kydMWNxz9QpvgoR2PFLsOXRo2pNM65g4jzokebn5cXRTc0A2cG2aMFHoY5pgoThj6Ye7zJAwwp0gbiNhSP9PzttzLki4jpM6H6TV50cEY8c1DPyXfP3_6dvhSXN9cXh3Orwsn6yoVnBttmHESOwGmqlQHWkphoDSs4U2Ludq67VzNkUEldAuu48BrpZzUspGn5OO97rI2E7Yu3x9gtEsYJghH62Gw_07m4aft_WbzG0Vd6iorfHhQCP7XijHZaYgOxxFm9Gu0wkihZFmXKqPv_0Nv_Rrm7C9TpcpkFs3U_p5ywccYsHu8hjN7F6q9C9U-hZo33v1t4pH_k6L8Dbv3nwM</recordid><startdate>20240305</startdate><enddate>20240305</enddate><creator>Chang, Soojeong</creator><creator>Shin, Kwang-Soo</creator><creator>Park, Bongju</creator><creator>Park, Seowoo</creator><creator>Shin, Jieun</creator><creator>Park, Hyemin</creator><creator>Jung, In Kyung</creator><creator>Kim, Jong Heon</creator><creator>Bae, Seong Eun</creator><creator>Kim, Jae-Ouk</creator><creator>Baek, Seung Ho</creator><creator>Kim, Green</creator><creator>Hong, Jung Joo</creator><creator>Seo, Hyungseok</creator><creator>Volz, Erik</creator><creator>Kang, Chang-Yuil</creator><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7020-2140</orcidid><orcidid>https://orcid.org/0009-0007-5351-3722</orcidid><orcidid>https://orcid.org/0000-0002-1843-6967</orcidid><orcidid>https://orcid.org/0000-0001-8062-470X</orcidid><orcidid>https://orcid.org/0009-0002-7055-1417</orcidid><orcidid>https://orcid.org/0000-0003-3294-6936</orcidid><orcidid>https://orcid.org/0009-0006-5244-4270</orcidid><orcidid>https://orcid.org/0009-0004-0819-3529</orcidid><orcidid>https://orcid.org/0000-0001-6268-8937</orcidid><orcidid>https://orcid.org/0000-0002-1961-6687</orcidid><orcidid>https://orcid.org/0000-0001-7897-4540</orcidid></search><sort><creationdate>20240305</creationdate><title>Strategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform</title><author>Chang, Soojeong ; 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These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants. We developed bivalent vaccine AdCLD-CoV19-1 BA.5/BA.2.75 and trivalent vaccines AdCLD-CoV19-1 XBB/BN.1/BQ.1.1 and AdCLD-CoV19-1 XBB.1.5/BN.1/BQ.1.1 using an Ad5/35 platform-based non-replicating recombinant adenoviral vector. We compared immune responses elicited by the monovalent and multivalent vaccines in mice and macaques. We found that the BA.5/BA.2.75 bivalent and the XBB/BN.1/BQ.1.1 and XBB.1.5/BN.1/BQ.1.1 trivalent vaccines exhibited improved cross-neutralization ability compared to their respective monovalent vaccines. 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| subjects | Animals Antibodies Antibodies, Neutralizing Antibodies, Viral Biological Sciences Coronaviruses COVID-19 COVID-19 - prevention & control COVID-19 vaccines COVID-19 Vaccines - genetics Humans Immune response Macaca Mice Neutralization SARS-CoV-2 - genetics Severe acute respiratory syndrome coronavirus 2 Vaccines Vaccines, Combined Viral diseases |
| title | Strategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform |
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