A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine
Abstract Background Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B. Methods Adults 18–49 years old (N =...
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| Veröffentlicht in: | The Journal of infectious diseases 2022-04, Vol.225 (8), p.1357-1366 |
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| creator | Walsh, Edward E Falsey, Ann R Scott, Daniel A Gurtman, Alejandra Zareba, Agnieszka M Jansen, Kathrin U Gruber, William C Dormitzer, Philip R Swanson, Kena A Radley, David Gomme, Emily Cooper, David Schmoele-Thoma, Beate |
| description | Abstract
Background
Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B.
Methods
Adults 18–49 years old (N = 618) were randomized to receive placebo or 60, 120, or 240 µg RSVpreF with or without Al(OH)3. Safety and immunogenicity were evaluated.
Results
RSVpreF recipients more frequently reported local reactions and systemic events than placebo recipients; these were mostly mild or moderate. No vaccine-related serious adverse events occurred through 12 months postvaccination. All RSVpreF formulations induced 1-month postvaccination virus-neutralizing titers higher than those associated with protection of high-risk infants by palivizumab, the only prophylactic currently available for RSV. Geometric mean fold rises (GMFRs) across RSVpreF doses/formulations were 10.6–16.9 for RSV A and 10.3–19.8 for RSV B at 1 month postvaccination, greater than those historically elicited by postfusion F vaccines. GMFRs were 3.9–5.2 and 3.7–5.1, respectively, at 12 months postvaccination.
Conclusions
RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults. These findings support development of RSVpreF, which is being evaluated in a pivotal phase 3 study for maternal immunization.
Clinical Trials Registration
NCT03529773.
Respiratory syncytial virus stabilized prefusion F subunit vaccine (RSVpreF) formulations were well tolerated and highly immunogenic in younger adults. These findings support further development of RSVpreF in a pivotal phase 3 study for maternal immunization. |
| doi_str_mv | 10.1093/infdis/jiab612 |
| format | Article |
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Background
Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B.
Methods
Adults 18–49 years old (N = 618) were randomized to receive placebo or 60, 120, or 240 µg RSVpreF with or without Al(OH)3. Safety and immunogenicity were evaluated.
Results
RSVpreF recipients more frequently reported local reactions and systemic events than placebo recipients; these were mostly mild or moderate. No vaccine-related serious adverse events occurred through 12 months postvaccination. All RSVpreF formulations induced 1-month postvaccination virus-neutralizing titers higher than those associated with protection of high-risk infants by palivizumab, the only prophylactic currently available for RSV. Geometric mean fold rises (GMFRs) across RSVpreF doses/formulations were 10.6–16.9 for RSV A and 10.3–19.8 for RSV B at 1 month postvaccination, greater than those historically elicited by postfusion F vaccines. GMFRs were 3.9–5.2 and 3.7–5.1, respectively, at 12 months postvaccination.
Conclusions
RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults. These findings support development of RSVpreF, which is being evaluated in a pivotal phase 3 study for maternal immunization.
Clinical Trials Registration
NCT03529773.
Respiratory syncytial virus stabilized prefusion F subunit vaccine (RSVpreF) formulations were well tolerated and highly immunogenic in younger adults. These findings support further development of RSVpreF in a pivotal phase 3 study for maternal immunization.</description><identifier>ISSN: 0022-1899</identifier><identifier>ISSN: 1537-6613</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiab612</identifier><identifier>PMID: 34932102</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adolescent ; Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; Antigens ; Clinical trials ; Editor's Choice ; Humans ; Immunization ; Immunogenicity ; Major and Brief Reports ; Middle Aged ; Monoclonal antibodies ; Placebos ; Respiratory syncytial virus ; Respiratory Syncytial Virus Infections - prevention & control ; Respiratory Syncytial Virus Vaccines ; Respiratory Syncytial Virus, Human ; Risk groups ; Vaccines ; Viral Fusion Proteins ; Viruses ; Young Adult</subject><ispartof>The Journal of infectious diseases, 2022-04, Vol.225 (8), p.1357-1366</ispartof><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-54c3a071e3d1bba60f228985a7823b395c11be5f45f6108059ad7ab992b062c03</citedby><cites>FETCH-LOGICAL-c452t-54c3a071e3d1bba60f228985a7823b395c11be5f45f6108059ad7ab992b062c03</cites><orcidid>0000-0002-8792-8877</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34932102$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Walsh, Edward E</creatorcontrib><creatorcontrib>Falsey, Ann R</creatorcontrib><creatorcontrib>Scott, Daniel A</creatorcontrib><creatorcontrib>Gurtman, Alejandra</creatorcontrib><creatorcontrib>Zareba, Agnieszka M</creatorcontrib><creatorcontrib>Jansen, Kathrin U</creatorcontrib><creatorcontrib>Gruber, William C</creatorcontrib><creatorcontrib>Dormitzer, Philip R</creatorcontrib><creatorcontrib>Swanson, Kena A</creatorcontrib><creatorcontrib>Radley, David</creatorcontrib><creatorcontrib>Gomme, Emily</creatorcontrib><creatorcontrib>Cooper, David</creatorcontrib><creatorcontrib>Schmoele-Thoma, Beate</creatorcontrib><title>A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract
Background
Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B.
Methods
Adults 18–49 years old (N = 618) were randomized to receive placebo or 60, 120, or 240 µg RSVpreF with or without Al(OH)3. Safety and immunogenicity were evaluated.
Results
RSVpreF recipients more frequently reported local reactions and systemic events than placebo recipients; these were mostly mild or moderate. No vaccine-related serious adverse events occurred through 12 months postvaccination. All RSVpreF formulations induced 1-month postvaccination virus-neutralizing titers higher than those associated with protection of high-risk infants by palivizumab, the only prophylactic currently available for RSV. Geometric mean fold rises (GMFRs) across RSVpreF doses/formulations were 10.6–16.9 for RSV A and 10.3–19.8 for RSV B at 1 month postvaccination, greater than those historically elicited by postfusion F vaccines. GMFRs were 3.9–5.2 and 3.7–5.1, respectively, at 12 months postvaccination.
Conclusions
RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults. These findings support development of RSVpreF, which is being evaluated in a pivotal phase 3 study for maternal immunization.
Clinical Trials Registration
NCT03529773.
Respiratory syncytial virus stabilized prefusion F subunit vaccine (RSVpreF) formulations were well tolerated and highly immunogenic in younger adults. These findings support further development of RSVpreF in a pivotal phase 3 study for maternal immunization.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antibodies, Neutralizing</subject><subject>Antibodies, Viral</subject><subject>Antigens</subject><subject>Clinical trials</subject><subject>Editor's Choice</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Major and Brief Reports</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Placebos</subject><subject>Respiratory syncytial virus</subject><subject>Respiratory Syncytial Virus Infections - prevention & control</subject><subject>Respiratory Syncytial Virus Vaccines</subject><subject>Respiratory Syncytial Virus, Human</subject><subject>Risk groups</subject><subject>Vaccines</subject><subject>Viral Fusion Proteins</subject><subject>Viruses</subject><subject>Young Adult</subject><issn>0022-1899</issn><issn>1537-6613</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EokvhyhFZ4kIP6Y7t2IkvSFVFAakSpYVerYnjUK-y9mInSOmvx2iXCrhwmsN882bmPUJeMjhloMXah6H3eb3x2CnGH5EVk6KplGLiMVkBcF6xVusj8iznDQDUQjVPyZGoteAM-Ip8PqPXGPq49feup1d3mB1la05vprlfaBwo0muXdz7hFNNCb5Zgl8njSG99mjO9Sm6Ys4-BXtBbtNYH95w8GXDM7sWhHpOvF---nH-oLj-9_3h-dlnZWvKpkrUVCA1zomddhwoGzlvdSmxaLjqhpWWsc3Ko5aAYtCA19g12WvMOFLcgjsnbve5u7rauty5MCUezS36LaTERvfm7E_yd-RZ_GA1M1XVTBN4cBFL8Prs8ma3P1o0jBhfnbHgxVDRN2V7Q1_-gmzinUN4rlNQAxWNVqNM9ZVPMuTjzcAwD8ysts0_LHNIqA6_-fOEB_x1PAU72QJx3_xP7CaLBn5M</recordid><startdate>20220419</startdate><enddate>20220419</enddate><creator>Walsh, Edward E</creator><creator>Falsey, Ann R</creator><creator>Scott, Daniel A</creator><creator>Gurtman, Alejandra</creator><creator>Zareba, Agnieszka M</creator><creator>Jansen, Kathrin U</creator><creator>Gruber, William C</creator><creator>Dormitzer, Philip R</creator><creator>Swanson, Kena A</creator><creator>Radley, David</creator><creator>Gomme, Emily</creator><creator>Cooper, David</creator><creator>Schmoele-Thoma, Beate</creator><general>Oxford University Press</general><scope>TOX</scope><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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8792-8877</orcidid></search><sort><creationdate>20220419</creationdate><title>A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine</title><author>Walsh, Edward E ; Falsey, Ann R ; Scott, Daniel A ; Gurtman, Alejandra ; Zareba, Agnieszka M ; Jansen, Kathrin U ; Gruber, William C ; Dormitzer, Philip R ; Swanson, Kena A ; Radley, David ; Gomme, Emily ; Cooper, David ; Schmoele-Thoma, Beate</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-54c3a071e3d1bba60f228985a7823b395c11be5f45f6108059ad7ab992b062c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antibodies, Neutralizing</topic><topic>Antibodies, Viral</topic><topic>Antigens</topic><topic>Clinical trials</topic><topic>Editor's Choice</topic><topic>Humans</topic><topic>Immunization</topic><topic>Immunogenicity</topic><topic>Major and Brief Reports</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Placebos</topic><topic>Respiratory syncytial virus</topic><topic>Respiratory Syncytial Virus Infections - prevention & control</topic><topic>Respiratory Syncytial Virus Vaccines</topic><topic>Respiratory Syncytial Virus, Human</topic><topic>Risk groups</topic><topic>Vaccines</topic><topic>Viral Fusion Proteins</topic><topic>Viruses</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Walsh, Edward E</creatorcontrib><creatorcontrib>Falsey, Ann R</creatorcontrib><creatorcontrib>Scott, Daniel A</creatorcontrib><creatorcontrib>Gurtman, Alejandra</creatorcontrib><creatorcontrib>Zareba, Agnieszka M</creatorcontrib><creatorcontrib>Jansen, Kathrin U</creatorcontrib><creatorcontrib>Gruber, William C</creatorcontrib><creatorcontrib>Dormitzer, Philip R</creatorcontrib><creatorcontrib>Swanson, Kena A</creatorcontrib><creatorcontrib>Radley, David</creatorcontrib><creatorcontrib>Gomme, Emily</creatorcontrib><creatorcontrib>Cooper, David</creatorcontrib><creatorcontrib>Schmoele-Thoma, Beate</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walsh, Edward E</au><au>Falsey, Ann R</au><au>Scott, Daniel A</au><au>Gurtman, Alejandra</au><au>Zareba, Agnieszka M</au><au>Jansen, Kathrin U</au><au>Gruber, William C</au><au>Dormitzer, Philip R</au><au>Swanson, Kena A</au><au>Radley, David</au><au>Gomme, Emily</au><au>Cooper, David</au><au>Schmoele-Thoma, Beate</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2022-04-19</date><risdate>2022</risdate><volume>225</volume><issue>8</issue><spage>1357</spage><epage>1366</epage><pages>1357-1366</pages><issn>0022-1899</issn><issn>1537-6613</issn><eissn>1537-6613</eissn><abstract>Abstract
Background
Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B.
Methods
Adults 18–49 years old (N = 618) were randomized to receive placebo or 60, 120, or 240 µg RSVpreF with or without Al(OH)3. Safety and immunogenicity were evaluated.
Results
RSVpreF recipients more frequently reported local reactions and systemic events than placebo recipients; these were mostly mild or moderate. No vaccine-related serious adverse events occurred through 12 months postvaccination. All RSVpreF formulations induced 1-month postvaccination virus-neutralizing titers higher than those associated with protection of high-risk infants by palivizumab, the only prophylactic currently available for RSV. Geometric mean fold rises (GMFRs) across RSVpreF doses/formulations were 10.6–16.9 for RSV A and 10.3–19.8 for RSV B at 1 month postvaccination, greater than those historically elicited by postfusion F vaccines. GMFRs were 3.9–5.2 and 3.7–5.1, respectively, at 12 months postvaccination.
Conclusions
RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults. These findings support development of RSVpreF, which is being evaluated in a pivotal phase 3 study for maternal immunization.
Clinical Trials Registration
NCT03529773.
Respiratory syncytial virus stabilized prefusion F subunit vaccine (RSVpreF) formulations were well tolerated and highly immunogenic in younger adults. These findings support further development of RSVpreF in a pivotal phase 3 study for maternal immunization.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>34932102</pmid><doi>10.1093/infdis/jiab612</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-8792-8877</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0022-1899 |
| ispartof | The Journal of infectious diseases, 2022-04, Vol.225 (8), p.1357-1366 |
| issn | 0022-1899 1537-6613 1537-6613 |
| language | eng |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
| subjects | Adolescent Adult Antibodies, Neutralizing Antibodies, Viral Antigens Clinical trials Editor's Choice Humans Immunization Immunogenicity Major and Brief Reports Middle Aged Monoclonal antibodies Placebos Respiratory syncytial virus Respiratory Syncytial Virus Infections - prevention & control Respiratory Syncytial Virus Vaccines Respiratory Syncytial Virus, Human Risk groups Vaccines Viral Fusion Proteins Viruses Young Adult |
| title | A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine |
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