Safety and immunogenicity of mRNA-based seasonal influenza vaccines formulated to include multiple A/H3N2 strains with or without the B/Yamagata strain in US adults aged 50–75 years: a phase 1/2, open-label, randomised trial
Inclusion of additional influenza A/H3N2 strains in seasonal influenza vaccines could expand coverage against multiple, antigenically distinct, cocirculating A/H3N2 clades and potentially replace the no longer circulating B/Yamagata strain. We aimed to evaluate the safety and immunogenicity of three...
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| Veröffentlicht in: | The Lancet infectious diseases 2025-01, Vol.25 (1), p.25-35 |
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| creator | Hsu, Denise Jayaraman, Akila Pucci, Alicia Joshi, Riya Mancini, Kevin Chen, Hui Ling Koslovsky, Kindra Mao, Xuezhou Choi, Angela Henry, Carole Vakil, Jignesh Stadlbauer, Daniel Jorquera, Patricia Arunkumar, Guha Asthagiri Sanchez-Crespo, Nelia E Wadsworth, L Tyler Bhupathy, Vellore Du, Evelyn Avanesov, Andrei Ananworanich, Jintanat Nachbagauer, Raffael |
| description | Inclusion of additional influenza A/H3N2 strains in seasonal influenza vaccines could expand coverage against multiple, antigenically distinct, cocirculating A/H3N2 clades and potentially replace the no longer circulating B/Yamagata strain. We aimed to evaluate the safety and immunogenicity of three next-generation seasonal influenza mRNA vaccines with different compositions that encode for haemagglutinins of multiple A/H3N2 strains, with or without the B/Yamagata strain, in adults.
This randomised, open-label, phase 1/2 trial enrolled healthy adults aged 50–75 years across 22 sites in the USA. Participants were randomly assigned (1:1:1:1:1:1:1) via interactive response technology to receive a single dose of mRNA-1011.1 (pentavalent; containing one additional A/H3N2 strain [Newcastle]), mRNA-1011.2 (quadrivalent; B/Yamagata replaced with one additional A/H3N2 strain [Newcastle]), mRNA-1012 at one of two dose levels (pentavalent; B/Yamagata replaced with two additional A/H3N2 strains [Newcastle and Hong Kong]), or one of three quadrivalent mRNA-1010 controls each encoding one of the A/H3N2 study strains. The primary outcomes were safety, evaluated in all randomly assigned participants who received a study vaccination (safety population), and reactogenicity, evaluated in all participants from the safety population who contributed any solicited adverse reaction data (solicited safety population). The secondary outcome was humoral immunogenicity of investigational mRNA vaccines at day 29 versus mRNA-1010 control vaccines based on haemagglutination inhibition antibody (HAI) assay in the per-protocol population. Here, we summarise findings from the planned interim analysis after participants had completed day 29. The study is registered with ClinicalTrials.gov, NCT05827068, and is ongoing.
Between March 27 and May 9, 2023, 1183 participants were screened for eligibility, 699 (59·1%) were randomly assigned, and 696 (58·8%) received vaccination (safety population, n=696; solicited safety population, n=694; per-protocol population, n=646). 382 (55%) of the 696 participants in the safety population self-reported as female and 314 (45%) as male. Frequencies of solicited adverse reactions were similar across vaccine groups; 551 (79%) of 694 participants reported at least one solicited adverse reaction within 7 days after vaccination and 83 (12%) of 696 participants reported at least one unsolicited adverse event within 28 days after vaccination. No vaccine-related ser |
| doi_str_mv | 10.1016/S1473-3099(24)00493-6 |
| format | Article |
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This randomised, open-label, phase 1/2 trial enrolled healthy adults aged 50–75 years across 22 sites in the USA. Participants were randomly assigned (1:1:1:1:1:1:1) via interactive response technology to receive a single dose of mRNA-1011.1 (pentavalent; containing one additional A/H3N2 strain [Newcastle]), mRNA-1011.2 (quadrivalent; B/Yamagata replaced with one additional A/H3N2 strain [Newcastle]), mRNA-1012 at one of two dose levels (pentavalent; B/Yamagata replaced with two additional A/H3N2 strains [Newcastle and Hong Kong]), or one of three quadrivalent mRNA-1010 controls each encoding one of the A/H3N2 study strains. The primary outcomes were safety, evaluated in all randomly assigned participants who received a study vaccination (safety population), and reactogenicity, evaluated in all participants from the safety population who contributed any solicited adverse reaction data (solicited safety population). The secondary outcome was humoral immunogenicity of investigational mRNA vaccines at day 29 versus mRNA-1010 control vaccines based on haemagglutination inhibition antibody (HAI) assay in the per-protocol population. Here, we summarise findings from the planned interim analysis after participants had completed day 29. The study is registered with ClinicalTrials.gov, NCT05827068, and is ongoing.
Between March 27 and May 9, 2023, 1183 participants were screened for eligibility, 699 (59·1%) were randomly assigned, and 696 (58·8%) received vaccination (safety population, n=696; solicited safety population, n=694; per-protocol population, n=646). 382 (55%) of the 696 participants in the safety population self-reported as female and 314 (45%) as male. Frequencies of solicited adverse reactions were similar across vaccine groups; 551 (79%) of 694 participants reported at least one solicited adverse reaction within 7 days after vaccination and 83 (12%) of 696 participants reported at least one unsolicited adverse event within 28 days after vaccination. No vaccine-related serious adverse events or deaths were reported. All three next-generation influenza vaccines elicited robust antibody responses against vaccine-matched influenza A and B strains at day 29 that were generally similar to mRNA-1010 controls, and higher responses against additional A/H3N2 strains that were not included within respective mRNA-1010 controls. Day 29 geometric mean fold rises in HAI titres from day 1 against vaccine-matched A/H3N2 strains were 3·0 (95% CI 2·6–3·6; Darwin) and 3·1 (2·6–3·8; Newcastle) for mRNA-1011.1; 3·3 (2·7–4·1; Darwin) and 4·2 (3·4–5·2; Newcastle) for mRNA-1011.2; 3·4 (2·9–4·0; Darwin), 4·5 (3·6–5·5; Newcastle), and 5·1 (4·2–6·2; Hong Kong) for mRNA-1012 50·0 μg; and 2·6 (2·2–3·1; Darwin), 3·7 (3·0–4·6; Newcastle), and 4·1 (3·3–5·1; Hong Kong) for mRNA-1012 62·5 μg. Inclusion of additional A/H3N2 strains did not reduce responses against influenza A/H1N1 or influenza B strains, and removal of B/Yamagata did not affect responses to B/Victoria.
These data support the continued clinical development of mRNA-based next-generation seasonal influenza vaccines with broadened influenza A/H3N2 strain coverage.
Moderna.</description><identifier>ISSN: 1473-3099</identifier><identifier>ISSN: 1474-4457</identifier><identifier>EISSN: 1474-4457</identifier><identifier>DOI: 10.1016/S1473-3099(24)00493-6</identifier><identifier>PMID: 39245055</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Adults ; Adverse events ; Aged ; Antibodies ; Antibodies, Viral - blood ; Antigens ; Clinical trials ; COVID-19 vaccines ; Effectiveness ; Female ; Health care ; Hemagglutination inhibition ; Hemagglutinins ; Humans ; Immunogenicity ; Immunogenicity, Vaccine ; Influenza ; Influenza A ; Influenza A Virus, H3N2 Subtype - genetics ; Influenza A Virus, H3N2 Subtype - immunology ; Influenza B ; Influenza B virus - genetics ; Influenza B virus - immunology ; Influenza Vaccines - administration & dosage ; Influenza Vaccines - adverse effects ; Influenza Vaccines - immunology ; Influenza, Human - immunology ; Influenza, Human - prevention & control ; Labels ; Male ; Middle Aged ; mRNA ; mRNA Vaccines ; Older people ; Pandemics ; Population studies ; Public health ; Regulatory approval ; RNA, Messenger - genetics ; RNA, Messenger - immunology ; Robust control ; Safety ; Side effects ; United States ; Vaccines ; Viruses</subject><ispartof>The Lancet infectious diseases, 2025-01, Vol.25 (1), p.25-35</ispartof><rights>2025 Elsevier Ltd</rights><rights>Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.</rights><rights>2025. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1865-7df91a7fdd08522021c79225de9c7a59bbc5594353302929b4d5d588d5fcfe283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S1473-3099(24)00493-6$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39245055$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsu, Denise</creatorcontrib><creatorcontrib>Jayaraman, Akila</creatorcontrib><creatorcontrib>Pucci, Alicia</creatorcontrib><creatorcontrib>Joshi, Riya</creatorcontrib><creatorcontrib>Mancini, Kevin</creatorcontrib><creatorcontrib>Chen, Hui Ling</creatorcontrib><creatorcontrib>Koslovsky, Kindra</creatorcontrib><creatorcontrib>Mao, Xuezhou</creatorcontrib><creatorcontrib>Choi, Angela</creatorcontrib><creatorcontrib>Henry, Carole</creatorcontrib><creatorcontrib>Vakil, Jignesh</creatorcontrib><creatorcontrib>Stadlbauer, Daniel</creatorcontrib><creatorcontrib>Jorquera, Patricia</creatorcontrib><creatorcontrib>Arunkumar, Guha Asthagiri</creatorcontrib><creatorcontrib>Sanchez-Crespo, Nelia E</creatorcontrib><creatorcontrib>Wadsworth, L Tyler</creatorcontrib><creatorcontrib>Bhupathy, Vellore</creatorcontrib><creatorcontrib>Du, Evelyn</creatorcontrib><creatorcontrib>Avanesov, Andrei</creatorcontrib><creatorcontrib>Ananworanich, Jintanat</creatorcontrib><creatorcontrib>Nachbagauer, Raffael</creatorcontrib><title>Safety and immunogenicity of mRNA-based seasonal influenza vaccines formulated to include multiple A/H3N2 strains with or without the B/Yamagata strain in US adults aged 50–75 years: a phase 1/2, open-label, randomised trial</title><title>The Lancet infectious diseases</title><addtitle>Lancet Infect Dis</addtitle><description>Inclusion of additional influenza A/H3N2 strains in seasonal influenza vaccines could expand coverage against multiple, antigenically distinct, cocirculating A/H3N2 clades and potentially replace the no longer circulating B/Yamagata strain. We aimed to evaluate the safety and immunogenicity of three next-generation seasonal influenza mRNA vaccines with different compositions that encode for haemagglutinins of multiple A/H3N2 strains, with or without the B/Yamagata strain, in adults.
This randomised, open-label, phase 1/2 trial enrolled healthy adults aged 50–75 years across 22 sites in the USA. Participants were randomly assigned (1:1:1:1:1:1:1) via interactive response technology to receive a single dose of mRNA-1011.1 (pentavalent; containing one additional A/H3N2 strain [Newcastle]), mRNA-1011.2 (quadrivalent; B/Yamagata replaced with one additional A/H3N2 strain [Newcastle]), mRNA-1012 at one of two dose levels (pentavalent; B/Yamagata replaced with two additional A/H3N2 strains [Newcastle and Hong Kong]), or one of three quadrivalent mRNA-1010 controls each encoding one of the A/H3N2 study strains. The primary outcomes were safety, evaluated in all randomly assigned participants who received a study vaccination (safety population), and reactogenicity, evaluated in all participants from the safety population who contributed any solicited adverse reaction data (solicited safety population). The secondary outcome was humoral immunogenicity of investigational mRNA vaccines at day 29 versus mRNA-1010 control vaccines based on haemagglutination inhibition antibody (HAI) assay in the per-protocol population. Here, we summarise findings from the planned interim analysis after participants had completed day 29. The study is registered with ClinicalTrials.gov, NCT05827068, and is ongoing.
Between March 27 and May 9, 2023, 1183 participants were screened for eligibility, 699 (59·1%) were randomly assigned, and 696 (58·8%) received vaccination (safety population, n=696; solicited safety population, n=694; per-protocol population, n=646). 382 (55%) of the 696 participants in the safety population self-reported as female and 314 (45%) as male. Frequencies of solicited adverse reactions were similar across vaccine groups; 551 (79%) of 694 participants reported at least one solicited adverse reaction within 7 days after vaccination and 83 (12%) of 696 participants reported at least one unsolicited adverse event within 28 days after vaccination. No vaccine-related serious adverse events or deaths were reported. All three next-generation influenza vaccines elicited robust antibody responses against vaccine-matched influenza A and B strains at day 29 that were generally similar to mRNA-1010 controls, and higher responses against additional A/H3N2 strains that were not included within respective mRNA-1010 controls. Day 29 geometric mean fold rises in HAI titres from day 1 against vaccine-matched A/H3N2 strains were 3·0 (95% CI 2·6–3·6; Darwin) and 3·1 (2·6–3·8; Newcastle) for mRNA-1011.1; 3·3 (2·7–4·1; Darwin) and 4·2 (3·4–5·2; Newcastle) for mRNA-1011.2; 3·4 (2·9–4·0; Darwin), 4·5 (3·6–5·5; Newcastle), and 5·1 (4·2–6·2; Hong Kong) for mRNA-1012 50·0 μg; and 2·6 (2·2–3·1; Darwin), 3·7 (3·0–4·6; Newcastle), and 4·1 (3·3–5·1; Hong Kong) for mRNA-1012 62·5 μg. Inclusion of additional A/H3N2 strains did not reduce responses against influenza A/H1N1 or influenza B strains, and removal of B/Yamagata did not affect responses to B/Victoria.
These data support the continued clinical development of mRNA-based next-generation seasonal influenza vaccines with broadened influenza A/H3N2 strain coverage.
Moderna.</description><subject>Adults</subject><subject>Adverse events</subject><subject>Aged</subject><subject>Antibodies</subject><subject>Antibodies, Viral - blood</subject><subject>Antigens</subject><subject>Clinical trials</subject><subject>COVID-19 vaccines</subject><subject>Effectiveness</subject><subject>Female</subject><subject>Health care</subject><subject>Hemagglutination inhibition</subject><subject>Hemagglutinins</subject><subject>Humans</subject><subject>Immunogenicity</subject><subject>Immunogenicity, Vaccine</subject><subject>Influenza</subject><subject>Influenza A</subject><subject>Influenza A Virus, H3N2 Subtype - genetics</subject><subject>Influenza A Virus, H3N2 Subtype - immunology</subject><subject>Influenza B</subject><subject>Influenza B virus - genetics</subject><subject>Influenza B virus - immunology</subject><subject>Influenza Vaccines - administration & dosage</subject><subject>Influenza Vaccines - adverse effects</subject><subject>Influenza Vaccines - immunology</subject><subject>Influenza, Human - immunology</subject><subject>Influenza, Human - prevention & control</subject><subject>Labels</subject><subject>Male</subject><subject>Middle Aged</subject><subject>mRNA</subject><subject>mRNA Vaccines</subject><subject>Older people</subject><subject>Pandemics</subject><subject>Population studies</subject><subject>Public health</subject><subject>Regulatory approval</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - immunology</subject><subject>Robust control</subject><subject>Safety</subject><subject>Side effects</subject><subject>United States</subject><subject>Vaccines</subject><subject>Viruses</subject><issn>1473-3099</issn><issn>1474-4457</issn><issn>1474-4457</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAQxyMEoqXwCCBLXIrUsLZjb9a9oKUCilQViaUHTtbEnuy6SuLFdoqWE-_AG_ZJ8H7AgQunsUa_-fs_H0XxnNHXjLLpZMFEXZUVVeqUi1eUClWV0wfFcU6LUghZP9y998hR8STGW0pZzah4XBxVigtJpTwu7hfQYtoQGCxxfT8OfomDMy6nfEv6z9fzsoGIlkSE6AfoiBvabsThB5A7MMYNGEnrQz92kDKWfAZMN1okOZXcukMyn1xW15zEFMANkXx3aUV82EU_JpJWSN5OvkIPS0hwwLIKuVkQsFkkElhmaUnvf_6qJdkghHhOgKxX2RlhE35G_BqHsoMGuzMSci--d1vTKTjonhaPWugiPjvEk-Lm_bsvF5fl1acPHy_mV6Vhs6ksa9sqBnVrLZ1JzilnplacS4vK1CBV0xgplahkVVGuuGqElVbOZla2pkU-q06K073uOvhvI8akswmDXQcD-jHqilFOaypVldGX_6C3fgx5ultKqKmSYkozJfeUCT7GgK1eB9dD2GhG9fYI9O4I9HbDmgu9OwI9zXUvDupj06P9W_Vn6xl4swcwj-POYdDROBwMWhfQJG29-88XvwFMrsL0</recordid><startdate>202501</startdate><enddate>202501</enddate><creator>Hsu, Denise</creator><creator>Jayaraman, Akila</creator><creator>Pucci, Alicia</creator><creator>Joshi, Riya</creator><creator>Mancini, Kevin</creator><creator>Chen, Hui Ling</creator><creator>Koslovsky, Kindra</creator><creator>Mao, Xuezhou</creator><creator>Choi, Angela</creator><creator>Henry, Carole</creator><creator>Vakil, Jignesh</creator><creator>Stadlbauer, Daniel</creator><creator>Jorquera, Patricia</creator><creator>Arunkumar, Guha Asthagiri</creator><creator>Sanchez-Crespo, Nelia E</creator><creator>Wadsworth, L Tyler</creator><creator>Bhupathy, Vellore</creator><creator>Du, Evelyn</creator><creator>Avanesov, Andrei</creator><creator>Ananworanich, Jintanat</creator><creator>Nachbagauer, Raffael</creator><general>Elsevier Ltd</general><general>Elsevier Limited</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>7QL</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>202501</creationdate><title>Safety and immunogenicity of mRNA-based seasonal influenza vaccines formulated to include multiple A/H3N2 strains with or without the B/Yamagata strain in US adults aged 50–75 years: a phase 1/2, open-label, randomised trial</title><author>Hsu, Denise ; Jayaraman, Akila ; Pucci, Alicia ; Joshi, Riya ; Mancini, Kevin ; Chen, Hui Ling ; Koslovsky, Kindra ; Mao, Xuezhou ; Choi, Angela ; Henry, Carole ; Vakil, Jignesh ; Stadlbauer, Daniel ; Jorquera, Patricia ; Arunkumar, Guha Asthagiri ; Sanchez-Crespo, Nelia E ; Wadsworth, L Tyler ; Bhupathy, Vellore ; Du, Evelyn ; Avanesov, Andrei ; Ananworanich, Jintanat ; Nachbagauer, Raffael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1865-7df91a7fdd08522021c79225de9c7a59bbc5594353302929b4d5d588d5fcfe283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Adults</topic><topic>Adverse events</topic><topic>Aged</topic><topic>Antibodies</topic><topic>Antibodies, Viral - blood</topic><topic>Antigens</topic><topic>Clinical trials</topic><topic>COVID-19 vaccines</topic><topic>Effectiveness</topic><topic>Female</topic><topic>Health care</topic><topic>Hemagglutination inhibition</topic><topic>Hemagglutinins</topic><topic>Humans</topic><topic>Immunogenicity</topic><topic>Immunogenicity, Vaccine</topic><topic>Influenza</topic><topic>Influenza A</topic><topic>Influenza A Virus, H3N2 Subtype - genetics</topic><topic>Influenza A Virus, H3N2 Subtype - immunology</topic><topic>Influenza B</topic><topic>Influenza B virus - genetics</topic><topic>Influenza B virus - immunology</topic><topic>Influenza Vaccines - administration & dosage</topic><topic>Influenza Vaccines - adverse effects</topic><topic>Influenza Vaccines - immunology</topic><topic>Influenza, Human - immunology</topic><topic>Influenza, Human - prevention & control</topic><topic>Labels</topic><topic>Male</topic><topic>Middle Aged</topic><topic>mRNA</topic><topic>mRNA Vaccines</topic><topic>Older people</topic><topic>Pandemics</topic><topic>Population studies</topic><topic>Public health</topic><topic>Regulatory approval</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - immunology</topic><topic>Robust control</topic><topic>Safety</topic><topic>Side effects</topic><topic>United States</topic><topic>Vaccines</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsu, Denise</creatorcontrib><creatorcontrib>Jayaraman, Akila</creatorcontrib><creatorcontrib>Pucci, Alicia</creatorcontrib><creatorcontrib>Joshi, Riya</creatorcontrib><creatorcontrib>Mancini, Kevin</creatorcontrib><creatorcontrib>Chen, Hui Ling</creatorcontrib><creatorcontrib>Koslovsky, Kindra</creatorcontrib><creatorcontrib>Mao, Xuezhou</creatorcontrib><creatorcontrib>Choi, Angela</creatorcontrib><creatorcontrib>Henry, Carole</creatorcontrib><creatorcontrib>Vakil, Jignesh</creatorcontrib><creatorcontrib>Stadlbauer, Daniel</creatorcontrib><creatorcontrib>Jorquera, Patricia</creatorcontrib><creatorcontrib>Arunkumar, Guha Asthagiri</creatorcontrib><creatorcontrib>Sanchez-Crespo, Nelia E</creatorcontrib><creatorcontrib>Wadsworth, L Tyler</creatorcontrib><creatorcontrib>Bhupathy, Vellore</creatorcontrib><creatorcontrib>Du, Evelyn</creatorcontrib><creatorcontrib>Avanesov, Andrei</creatorcontrib><creatorcontrib>Ananworanich, Jintanat</creatorcontrib><creatorcontrib>Nachbagauer, Raffael</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsu, Denise</au><au>Jayaraman, Akila</au><au>Pucci, Alicia</au><au>Joshi, Riya</au><au>Mancini, Kevin</au><au>Chen, Hui Ling</au><au>Koslovsky, Kindra</au><au>Mao, Xuezhou</au><au>Choi, Angela</au><au>Henry, Carole</au><au>Vakil, Jignesh</au><au>Stadlbauer, Daniel</au><au>Jorquera, Patricia</au><au>Arunkumar, Guha Asthagiri</au><au>Sanchez-Crespo, Nelia E</au><au>Wadsworth, L Tyler</au><au>Bhupathy, Vellore</au><au>Du, Evelyn</au><au>Avanesov, Andrei</au><au>Ananworanich, Jintanat</au><au>Nachbagauer, Raffael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety and immunogenicity of mRNA-based seasonal influenza vaccines formulated to include multiple A/H3N2 strains with or without the B/Yamagata strain in US adults aged 50–75 years: a phase 1/2, open-label, randomised trial</atitle><jtitle>The Lancet infectious diseases</jtitle><addtitle>Lancet Infect Dis</addtitle><date>2025-01</date><risdate>2025</risdate><volume>25</volume><issue>1</issue><spage>25</spage><epage>35</epage><pages>25-35</pages><issn>1473-3099</issn><issn>1474-4457</issn><eissn>1474-4457</eissn><abstract>Inclusion of additional influenza A/H3N2 strains in seasonal influenza vaccines could expand coverage against multiple, antigenically distinct, cocirculating A/H3N2 clades and potentially replace the no longer circulating B/Yamagata strain. We aimed to evaluate the safety and immunogenicity of three next-generation seasonal influenza mRNA vaccines with different compositions that encode for haemagglutinins of multiple A/H3N2 strains, with or without the B/Yamagata strain, in adults.
This randomised, open-label, phase 1/2 trial enrolled healthy adults aged 50–75 years across 22 sites in the USA. Participants were randomly assigned (1:1:1:1:1:1:1) via interactive response technology to receive a single dose of mRNA-1011.1 (pentavalent; containing one additional A/H3N2 strain [Newcastle]), mRNA-1011.2 (quadrivalent; B/Yamagata replaced with one additional A/H3N2 strain [Newcastle]), mRNA-1012 at one of two dose levels (pentavalent; B/Yamagata replaced with two additional A/H3N2 strains [Newcastle and Hong Kong]), or one of three quadrivalent mRNA-1010 controls each encoding one of the A/H3N2 study strains. The primary outcomes were safety, evaluated in all randomly assigned participants who received a study vaccination (safety population), and reactogenicity, evaluated in all participants from the safety population who contributed any solicited adverse reaction data (solicited safety population). The secondary outcome was humoral immunogenicity of investigational mRNA vaccines at day 29 versus mRNA-1010 control vaccines based on haemagglutination inhibition antibody (HAI) assay in the per-protocol population. Here, we summarise findings from the planned interim analysis after participants had completed day 29. The study is registered with ClinicalTrials.gov, NCT05827068, and is ongoing.
Between March 27 and May 9, 2023, 1183 participants were screened for eligibility, 699 (59·1%) were randomly assigned, and 696 (58·8%) received vaccination (safety population, n=696; solicited safety population, n=694; per-protocol population, n=646). 382 (55%) of the 696 participants in the safety population self-reported as female and 314 (45%) as male. Frequencies of solicited adverse reactions were similar across vaccine groups; 551 (79%) of 694 participants reported at least one solicited adverse reaction within 7 days after vaccination and 83 (12%) of 696 participants reported at least one unsolicited adverse event within 28 days after vaccination. No vaccine-related serious adverse events or deaths were reported. All three next-generation influenza vaccines elicited robust antibody responses against vaccine-matched influenza A and B strains at day 29 that were generally similar to mRNA-1010 controls, and higher responses against additional A/H3N2 strains that were not included within respective mRNA-1010 controls. Day 29 geometric mean fold rises in HAI titres from day 1 against vaccine-matched A/H3N2 strains were 3·0 (95% CI 2·6–3·6; Darwin) and 3·1 (2·6–3·8; Newcastle) for mRNA-1011.1; 3·3 (2·7–4·1; Darwin) and 4·2 (3·4–5·2; Newcastle) for mRNA-1011.2; 3·4 (2·9–4·0; Darwin), 4·5 (3·6–5·5; Newcastle), and 5·1 (4·2–6·2; Hong Kong) for mRNA-1012 50·0 μg; and 2·6 (2·2–3·1; Darwin), 3·7 (3·0–4·6; Newcastle), and 4·1 (3·3–5·1; Hong Kong) for mRNA-1012 62·5 μg. Inclusion of additional A/H3N2 strains did not reduce responses against influenza A/H1N1 or influenza B strains, and removal of B/Yamagata did not affect responses to B/Victoria.
These data support the continued clinical development of mRNA-based next-generation seasonal influenza vaccines with broadened influenza A/H3N2 strain coverage.
Moderna.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>39245055</pmid><doi>10.1016/S1473-3099(24)00493-6</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1473-3099 |
| ispartof | The Lancet infectious diseases, 2025-01, Vol.25 (1), p.25-35 |
| issn | 1473-3099 1474-4457 1474-4457 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3102070593 |
| source | Elsevier ScienceDirect Journals Complete - AutoHoldings; MEDLINE |
| subjects | Adults Adverse events Aged Antibodies Antibodies, Viral - blood Antigens Clinical trials COVID-19 vaccines Effectiveness Female Health care Hemagglutination inhibition Hemagglutinins Humans Immunogenicity Immunogenicity, Vaccine Influenza Influenza A Influenza A Virus, H3N2 Subtype - genetics Influenza A Virus, H3N2 Subtype - immunology Influenza B Influenza B virus - genetics Influenza B virus - immunology Influenza Vaccines - administration & dosage Influenza Vaccines - adverse effects Influenza Vaccines - immunology Influenza, Human - immunology Influenza, Human - prevention & control Labels Male Middle Aged mRNA mRNA Vaccines Older people Pandemics Population studies Public health Regulatory approval RNA, Messenger - genetics RNA, Messenger - immunology Robust control Safety Side effects United States Vaccines Viruses |
| title | Safety and immunogenicity of mRNA-based seasonal influenza vaccines formulated to include multiple A/H3N2 strains with or without the B/Yamagata strain in US adults aged 50–75 years: a phase 1/2, open-label, randomised trial |
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