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Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost...

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Autores principales: Branche, Angela R., Rouphael, Nadine G., Diemert, David J., Falsey, Ann R., Losada, Cecilia, Baden, Lindsey R., Frey, Sharon E., Whitaker, Jennifer A., Little, Susan J., Anderson, Evan J., Walter, Emmanuel B., Novak, Richard M., Rupp, Richard, Jackson, Lisa A., Babu, Tara M., Kottkamp, Angelica C., Luetkemeyer, Anne F., Immergluck, Lilly C., Presti, Rachel M., Bäcker, Martín, Winokur, Patricia L., Mahgoub, Siham M., Goepfert, Paul A., Fusco, Dahlene N., Malkin, Elissa, Bethony, Jeffrey M., Walsh, Edward E., Graciaa, Daniel S., Samaha, Hady, Sherman, Amy C., Walsh, Stephen R., Abate, Getahun, Oikonomopoulou, Zacharoula, El Sahly, Hana M., Martin, Thomas C. S., Kamidani, Satoshi, Smith, Michael J., Ladner, Benjamin G., Porterfield, Laura, Dunstan, Maya, Wald, Anna, Davis, Tamia, Atmar, Robert L., Mulligan, Mark J., Lyke, Kirsten E., Posavad, Christine M., Meagher, Megan A., Stephens, David S., Neuzil, Kathleen M., Abebe, Kuleni, Hill, Heather, Albert, Jim, Telu, Kalyani, Mu, Jinjian, Lewis, Teri C., Giebeig, Lisa A., Eaton, Amanda, Netzl, Antonia, Wilks, Samuel H., Türeli, Sina, Makhene, Mamodikoe, Crandon, Sonja, Montefiori, David C., Makowski, Mat, Smith, Derek J., Nayak, Seema U., Roberts, Paul C., Beigel, John H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504073/
https://www.ncbi.nlm.nih.gov/pubmed/37640860
http://dx.doi.org/10.1038/s41591-023-02503-4
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author Branche, Angela R.
Rouphael, Nadine G.
Diemert, David J.
Falsey, Ann R.
Losada, Cecilia
Baden, Lindsey R.
Frey, Sharon E.
Whitaker, Jennifer A.
Little, Susan J.
Anderson, Evan J.
Walter, Emmanuel B.
Novak, Richard M.
Rupp, Richard
Jackson, Lisa A.
Babu, Tara M.
Kottkamp, Angelica C.
Luetkemeyer, Anne F.
Immergluck, Lilly C.
Presti, Rachel M.
Bäcker, Martín
Winokur, Patricia L.
Mahgoub, Siham M.
Goepfert, Paul A.
Fusco, Dahlene N.
Malkin, Elissa
Bethony, Jeffrey M.
Walsh, Edward E.
Graciaa, Daniel S.
Samaha, Hady
Sherman, Amy C.
Walsh, Stephen R.
Abate, Getahun
Oikonomopoulou, Zacharoula
El Sahly, Hana M.
Martin, Thomas C. S.
Kamidani, Satoshi
Smith, Michael J.
Ladner, Benjamin G.
Porterfield, Laura
Dunstan, Maya
Wald, Anna
Davis, Tamia
Atmar, Robert L.
Mulligan, Mark J.
Lyke, Kirsten E.
Posavad, Christine M.
Meagher, Megan A.
Stephens, David S.
Neuzil, Kathleen M.
Abebe, Kuleni
Hill, Heather
Albert, Jim
Telu, Kalyani
Mu, Jinjian
Lewis, Teri C.
Giebeig, Lisa A.
Eaton, Amanda
Netzl, Antonia
Wilks, Samuel H.
Türeli, Sina
Makhene, Mamodikoe
Crandon, Sonja
Montefiori, David C.
Makowski, Mat
Smith, Derek J.
Nayak, Seema U.
Roberts, Paul C.
Beigel, John H.
author_facet Branche, Angela R.
Rouphael, Nadine G.
Diemert, David J.
Falsey, Ann R.
Losada, Cecilia
Baden, Lindsey R.
Frey, Sharon E.
Whitaker, Jennifer A.
Little, Susan J.
Anderson, Evan J.
Walter, Emmanuel B.
Novak, Richard M.
Rupp, Richard
Jackson, Lisa A.
Babu, Tara M.
Kottkamp, Angelica C.
Luetkemeyer, Anne F.
Immergluck, Lilly C.
Presti, Rachel M.
Bäcker, Martín
Winokur, Patricia L.
Mahgoub, Siham M.
Goepfert, Paul A.
Fusco, Dahlene N.
Malkin, Elissa
Bethony, Jeffrey M.
Walsh, Edward E.
Graciaa, Daniel S.
Samaha, Hady
Sherman, Amy C.
Walsh, Stephen R.
Abate, Getahun
Oikonomopoulou, Zacharoula
El Sahly, Hana M.
Martin, Thomas C. S.
Kamidani, Satoshi
Smith, Michael J.
Ladner, Benjamin G.
Porterfield, Laura
Dunstan, Maya
Wald, Anna
Davis, Tamia
Atmar, Robert L.
Mulligan, Mark J.
Lyke, Kirsten E.
Posavad, Christine M.
Meagher, Megan A.
Stephens, David S.
Neuzil, Kathleen M.
Abebe, Kuleni
Hill, Heather
Albert, Jim
Telu, Kalyani
Mu, Jinjian
Lewis, Teri C.
Giebeig, Lisa A.
Eaton, Amanda
Netzl, Antonia
Wilks, Samuel H.
Türeli, Sina
Makhene, Mamodikoe
Crandon, Sonja
Montefiori, David C.
Makowski, Mat
Smith, Derek J.
Nayak, Seema U.
Roberts, Paul C.
Beigel, John H.
author_sort Branche, Angela R.
collection PubMed
description Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID(50) titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID(50) titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037.
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spelling pubmed-105040732023-09-17 Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial Branche, Angela R. Rouphael, Nadine G. Diemert, David J. Falsey, Ann R. Losada, Cecilia Baden, Lindsey R. Frey, Sharon E. Whitaker, Jennifer A. Little, Susan J. Anderson, Evan J. Walter, Emmanuel B. Novak, Richard M. Rupp, Richard Jackson, Lisa A. Babu, Tara M. Kottkamp, Angelica C. Luetkemeyer, Anne F. Immergluck, Lilly C. Presti, Rachel M. Bäcker, Martín Winokur, Patricia L. Mahgoub, Siham M. Goepfert, Paul A. Fusco, Dahlene N. Malkin, Elissa Bethony, Jeffrey M. Walsh, Edward E. Graciaa, Daniel S. Samaha, Hady Sherman, Amy C. Walsh, Stephen R. Abate, Getahun Oikonomopoulou, Zacharoula El Sahly, Hana M. Martin, Thomas C. S. Kamidani, Satoshi Smith, Michael J. Ladner, Benjamin G. Porterfield, Laura Dunstan, Maya Wald, Anna Davis, Tamia Atmar, Robert L. Mulligan, Mark J. Lyke, Kirsten E. Posavad, Christine M. Meagher, Megan A. Stephens, David S. Neuzil, Kathleen M. Abebe, Kuleni Hill, Heather Albert, Jim Telu, Kalyani Mu, Jinjian Lewis, Teri C. Giebeig, Lisa A. Eaton, Amanda Netzl, Antonia Wilks, Samuel H. Türeli, Sina Makhene, Mamodikoe Crandon, Sonja Montefiori, David C. Makowski, Mat Smith, Derek J. Nayak, Seema U. Roberts, Paul C. Beigel, John H. Nat Med Article Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID(50) titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID(50) titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037. Nature Publishing Group US 2023-08-28 2023 /pmc/articles/PMC10504073/ /pubmed/37640860 http://dx.doi.org/10.1038/s41591-023-02503-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Branche, Angela R.
Rouphael, Nadine G.
Diemert, David J.
Falsey, Ann R.
Losada, Cecilia
Baden, Lindsey R.
Frey, Sharon E.
Whitaker, Jennifer A.
Little, Susan J.
Anderson, Evan J.
Walter, Emmanuel B.
Novak, Richard M.
Rupp, Richard
Jackson, Lisa A.
Babu, Tara M.
Kottkamp, Angelica C.
Luetkemeyer, Anne F.
Immergluck, Lilly C.
Presti, Rachel M.
Bäcker, Martín
Winokur, Patricia L.
Mahgoub, Siham M.
Goepfert, Paul A.
Fusco, Dahlene N.
Malkin, Elissa
Bethony, Jeffrey M.
Walsh, Edward E.
Graciaa, Daniel S.
Samaha, Hady
Sherman, Amy C.
Walsh, Stephen R.
Abate, Getahun
Oikonomopoulou, Zacharoula
El Sahly, Hana M.
Martin, Thomas C. S.
Kamidani, Satoshi
Smith, Michael J.
Ladner, Benjamin G.
Porterfield, Laura
Dunstan, Maya
Wald, Anna
Davis, Tamia
Atmar, Robert L.
Mulligan, Mark J.
Lyke, Kirsten E.
Posavad, Christine M.
Meagher, Megan A.
Stephens, David S.
Neuzil, Kathleen M.
Abebe, Kuleni
Hill, Heather
Albert, Jim
Telu, Kalyani
Mu, Jinjian
Lewis, Teri C.
Giebeig, Lisa A.
Eaton, Amanda
Netzl, Antonia
Wilks, Samuel H.
Türeli, Sina
Makhene, Mamodikoe
Crandon, Sonja
Montefiori, David C.
Makowski, Mat
Smith, Derek J.
Nayak, Seema U.
Roberts, Paul C.
Beigel, John H.
Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
title Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
title_full Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
title_fullStr Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
title_full_unstemmed Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
title_short Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
title_sort comparison of bivalent and monovalent sars-cov-2 variant vaccines: the phase 2 randomized open-label covail trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504073/
https://www.ncbi.nlm.nih.gov/pubmed/37640860
http://dx.doi.org/10.1038/s41591-023-02503-4
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