Live-attenuated Vaccines Prevent Respiratory Syncytial Virus-associated Illness in Young Children
Active immunization is needed to protect infants and young children against respiratory syncytial virus (RSV). Rationally designed live-attenuated RSV vaccines are in clinical development. Develop preliminary estimates of vaccine efficacy, assess durability of antibody responses to vaccination and &...
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| Veröffentlicht in: | American journal of respiratory and critical care medicine 2021-03, Vol.203 (5), p.594-603 |
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| creator | Karron, Ruth A Atwell, Jessica E McFarland, Elizabeth J Cunningham, Coleen K Muresan, Petronella Perlowski, Charlotte Libous, Jennifer Spector, Stephen A Yogev, Ram Aziz, Mariam Woods, Suzanne Wanionek, Kimberli Collins, Peter L Buchholz, Ursula J |
| description | Active immunization is needed to protect infants and young children against respiratory syncytial virus (RSV). Rationally designed live-attenuated RSV vaccines are in clinical development.
Develop preliminary estimates of vaccine efficacy, assess durability of antibody responses to vaccination and "booster" responses after natural RSV infection, and determine sample sizes needed for more precise estimates of vaccine efficacy.
We analyzed data from seven phase 1 trials of live-attenuated RSV vaccines in 6- to 24-month-old children (
= 239).
The five vaccine regimens that induced neutralizing antibody responses in ≥80% of vaccinees (defined
as "more promising") protected against RSV-associated medically attended acute respiratory illness (RSV-MAARI) and medically attended acute lower respiratory illness (RSV-MAALRI) and primed for potent anamnestic responses upon natural exposure to wild-type RSV. Among recipients of "more promising" RSV vaccines, efficacy against RSV-MAARI was 67% (95% confidence interval [CI], 24 to 85;
= 0.008) and against RSV-MAALRI was 88% (95% CI, -9 to 99;
= 0.04). A greater than or equal to fourfold increase in RSV serum neutralizing antibody following vaccination was strongly associated with protection against RSV-MAARI (odds ratio, 0.26; 95% CI, 0.09 to 0.75;
= 0.014) and RSV-MAALRI; no child with a greater than or equal to fourfold increase developed RSV-MAALRI. Rates of RSV-MAARI and RSV-MAALRI in placebo recipients were 21% and 7%, respectively. Given these rates, a study of 540 RSV-naive children would have 90% power to demonstrate ≥55% efficacy against RSV-MAARI and ≥80% efficacy against RSV-MAALRI; if rates were 10% and 3%, a study of 1,300 RSV-naive children would be needed.
Rapid development of a live-attenuated RSV vaccine could contribute substantially to reducing the global burden of RSV disease. |
| doi_str_mv | 10.1164/rccm.202005-1660OC |
| format | Article |
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Develop preliminary estimates of vaccine efficacy, assess durability of antibody responses to vaccination and "booster" responses after natural RSV infection, and determine sample sizes needed for more precise estimates of vaccine efficacy.
We analyzed data from seven phase 1 trials of live-attenuated RSV vaccines in 6- to 24-month-old children (
= 239).
The five vaccine regimens that induced neutralizing antibody responses in ≥80% of vaccinees (defined
as "more promising") protected against RSV-associated medically attended acute respiratory illness (RSV-MAARI) and medically attended acute lower respiratory illness (RSV-MAALRI) and primed for potent anamnestic responses upon natural exposure to wild-type RSV. Among recipients of "more promising" RSV vaccines, efficacy against RSV-MAARI was 67% (95% confidence interval [CI], 24 to 85;
= 0.008) and against RSV-MAALRI was 88% (95% CI, -9 to 99;
= 0.04). A greater than or equal to fourfold increase in RSV serum neutralizing antibody following vaccination was strongly associated with protection against RSV-MAARI (odds ratio, 0.26; 95% CI, 0.09 to 0.75;
= 0.014) and RSV-MAALRI; no child with a greater than or equal to fourfold increase developed RSV-MAALRI. Rates of RSV-MAARI and RSV-MAALRI in placebo recipients were 21% and 7%, respectively. Given these rates, a study of 540 RSV-naive children would have 90% power to demonstrate ≥55% efficacy against RSV-MAARI and ≥80% efficacy against RSV-MAALRI; if rates were 10% and 3%, a study of 1,300 RSV-naive children would be needed.
Rapid development of a live-attenuated RSV vaccine could contribute substantially to reducing the global burden of RSV disease.</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.202005-1660OC</identifier><identifier>PMID: 32871092</identifier><language>eng</language><publisher>United States: American Thoracic Society</publisher><subject>Antibodies, Neutralizing - immunology ; Antibodies, Viral - immunology ; Clinical Trials, Phase I as Topic ; Disease prevention ; Female ; Humans ; Immunization ; Immunogenicity, Vaccine - immunology ; Immunologic Memory - immunology ; Infant ; Male ; Original ; Pediatrics ; Randomized Controlled Trials as Topic ; Respiratory syncytial virus ; Respiratory Syncytial Virus Infections - physiopathology ; Respiratory Syncytial Virus Infections - prevention & control ; Respiratory Syncytial Virus Vaccines - therapeutic use ; Respiratory Syncytial Virus, Human - immunology ; Treatment Outcome ; Vaccines ; Vaccines, Attenuated - therapeutic use</subject><ispartof>American journal of respiratory and critical care medicine, 2021-03, Vol.203 (5), p.594-603</ispartof><rights>Copyright American Thoracic Society Mar 1, 2021</rights><rights>Copyright © 2021 by the American Thoracic Society 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-76bf372f5ca27d2aaaf2c44d4296aa719b351d96c59afe276e4b20aa8842e8cc3</citedby><cites>FETCH-LOGICAL-c430t-76bf372f5ca27d2aaaf2c44d4296aa719b351d96c59afe276e4b20aa8842e8cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,4025,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32871092$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karron, Ruth A</creatorcontrib><creatorcontrib>Atwell, Jessica E</creatorcontrib><creatorcontrib>McFarland, Elizabeth J</creatorcontrib><creatorcontrib>Cunningham, Coleen K</creatorcontrib><creatorcontrib>Muresan, Petronella</creatorcontrib><creatorcontrib>Perlowski, Charlotte</creatorcontrib><creatorcontrib>Libous, Jennifer</creatorcontrib><creatorcontrib>Spector, Stephen A</creatorcontrib><creatorcontrib>Yogev, Ram</creatorcontrib><creatorcontrib>Aziz, Mariam</creatorcontrib><creatorcontrib>Woods, Suzanne</creatorcontrib><creatorcontrib>Wanionek, Kimberli</creatorcontrib><creatorcontrib>Collins, Peter L</creatorcontrib><creatorcontrib>Buchholz, Ursula J</creatorcontrib><title>Live-attenuated Vaccines Prevent Respiratory Syncytial Virus-associated Illness in Young Children</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>Active immunization is needed to protect infants and young children against respiratory syncytial virus (RSV). Rationally designed live-attenuated RSV vaccines are in clinical development.
Develop preliminary estimates of vaccine efficacy, assess durability of antibody responses to vaccination and "booster" responses after natural RSV infection, and determine sample sizes needed for more precise estimates of vaccine efficacy.
We analyzed data from seven phase 1 trials of live-attenuated RSV vaccines in 6- to 24-month-old children (
= 239).
The five vaccine regimens that induced neutralizing antibody responses in ≥80% of vaccinees (defined
as "more promising") protected against RSV-associated medically attended acute respiratory illness (RSV-MAARI) and medically attended acute lower respiratory illness (RSV-MAALRI) and primed for potent anamnestic responses upon natural exposure to wild-type RSV. Among recipients of "more promising" RSV vaccines, efficacy against RSV-MAARI was 67% (95% confidence interval [CI], 24 to 85;
= 0.008) and against RSV-MAALRI was 88% (95% CI, -9 to 99;
= 0.04). A greater than or equal to fourfold increase in RSV serum neutralizing antibody following vaccination was strongly associated with protection against RSV-MAARI (odds ratio, 0.26; 95% CI, 0.09 to 0.75;
= 0.014) and RSV-MAALRI; no child with a greater than or equal to fourfold increase developed RSV-MAALRI. Rates of RSV-MAARI and RSV-MAALRI in placebo recipients were 21% and 7%, respectively. Given these rates, a study of 540 RSV-naive children would have 90% power to demonstrate ≥55% efficacy against RSV-MAARI and ≥80% efficacy against RSV-MAALRI; if rates were 10% and 3%, a study of 1,300 RSV-naive children would be needed.
Rapid development of a live-attenuated RSV vaccine could contribute substantially to reducing the global burden of RSV disease.</description><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Viral - immunology</subject><subject>Clinical Trials, Phase I as Topic</subject><subject>Disease prevention</subject><subject>Female</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunogenicity, Vaccine - immunology</subject><subject>Immunologic Memory - immunology</subject><subject>Infant</subject><subject>Male</subject><subject>Original</subject><subject>Pediatrics</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Respiratory syncytial virus</subject><subject>Respiratory Syncytial Virus Infections - physiopathology</subject><subject>Respiratory Syncytial Virus Infections - prevention & control</subject><subject>Respiratory Syncytial Virus Vaccines - therapeutic use</subject><subject>Respiratory Syncytial Virus, Human - immunology</subject><subject>Treatment Outcome</subject><subject>Vaccines</subject><subject>Vaccines, Attenuated - therapeutic use</subject><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1rFEEQxRtRzIf-Ax5kwIuXSfq7py-CLGoCC5FEg56a2p6apMNs99o9s7D_vR03huipCur3Hq94hLxh9IQxLU-z9-sTTjmlqmVa04vFM3LIlFCttIY-rzs1opXS_jggR6XcUcp4x-hLciB4Zxi1_JDAMmyxhWnCOMOEfXMN3oeIpfmacYtxai6xbEKGKeVdc7WLfjcFGJvrkOfSQinJhz-683GsqtKE2PxMc7xpFrdh7DPGV-TFAGPB1w_zmHz__Onb4qxdXnw5X3xctl4KOrVGrwZh-KA8cNNzABi4l7KX3GoAw-xKKNZb7ZWFAbnRKFecAnSd5Nh5L47Jh73vZl6tsfc1e4bRbXJYQ965BMH9e4nh1t2krTOWS6W7avD-wSCnXzOWya1D8TiOEDHNxXEprBacClXRd_-hd2nOsb5XKVsTaaZopfie8jmVknF4DMOou2_Q3Tfo9g26fYNV9PbpG4-Sv5WJ34memoA</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Karron, Ruth A</creator><creator>Atwell, Jessica E</creator><creator>McFarland, Elizabeth J</creator><creator>Cunningham, Coleen K</creator><creator>Muresan, Petronella</creator><creator>Perlowski, Charlotte</creator><creator>Libous, Jennifer</creator><creator>Spector, Stephen A</creator><creator>Yogev, Ram</creator><creator>Aziz, Mariam</creator><creator>Woods, Suzanne</creator><creator>Wanionek, Kimberli</creator><creator>Collins, Peter L</creator><creator>Buchholz, Ursula J</creator><general>American Thoracic Society</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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210301</creationdate><title>Live-attenuated Vaccines Prevent Respiratory Syncytial Virus-associated Illness in Young Children</title><author>Karron, Ruth A ; 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Rationally designed live-attenuated RSV vaccines are in clinical development.
Develop preliminary estimates of vaccine efficacy, assess durability of antibody responses to vaccination and "booster" responses after natural RSV infection, and determine sample sizes needed for more precise estimates of vaccine efficacy.
We analyzed data from seven phase 1 trials of live-attenuated RSV vaccines in 6- to 24-month-old children (
= 239).
The five vaccine regimens that induced neutralizing antibody responses in ≥80% of vaccinees (defined
as "more promising") protected against RSV-associated medically attended acute respiratory illness (RSV-MAARI) and medically attended acute lower respiratory illness (RSV-MAALRI) and primed for potent anamnestic responses upon natural exposure to wild-type RSV. Among recipients of "more promising" RSV vaccines, efficacy against RSV-MAARI was 67% (95% confidence interval [CI], 24 to 85;
= 0.008) and against RSV-MAALRI was 88% (95% CI, -9 to 99;
= 0.04). A greater than or equal to fourfold increase in RSV serum neutralizing antibody following vaccination was strongly associated with protection against RSV-MAARI (odds ratio, 0.26; 95% CI, 0.09 to 0.75;
= 0.014) and RSV-MAALRI; no child with a greater than or equal to fourfold increase developed RSV-MAALRI. Rates of RSV-MAARI and RSV-MAALRI in placebo recipients were 21% and 7%, respectively. Given these rates, a study of 540 RSV-naive children would have 90% power to demonstrate ≥55% efficacy against RSV-MAARI and ≥80% efficacy against RSV-MAALRI; if rates were 10% and 3%, a study of 1,300 RSV-naive children would be needed.
Rapid development of a live-attenuated RSV vaccine could contribute substantially to reducing the global burden of RSV disease.</abstract><cop>United States</cop><pub>American Thoracic Society</pub><pmid>32871092</pmid><doi>10.1164/rccm.202005-1660OC</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1073-449X |
| ispartof | American journal of respiratory and critical care medicine, 2021-03, Vol.203 (5), p.594-603 |
| issn | 1073-449X 1535-4970 |
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| source | MEDLINE; American Thoracic Society (ATS) Journals Online; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Clinical Trials, Phase I as Topic Disease prevention Female Humans Immunization Immunogenicity, Vaccine - immunology Immunologic Memory - immunology Infant Male Original Pediatrics Randomized Controlled Trials as Topic Respiratory syncytial virus Respiratory Syncytial Virus Infections - physiopathology Respiratory Syncytial Virus Infections - prevention & control Respiratory Syncytial Virus Vaccines - therapeutic use Respiratory Syncytial Virus, Human - immunology Treatment Outcome Vaccines Vaccines, Attenuated - therapeutic use |
| title | Live-attenuated Vaccines Prevent Respiratory Syncytial Virus-associated Illness in Young Children |
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