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

Angela R. Branche; Nadine G. Rouphael; David J. Diemert; Ann R. Falsey; Cecilia Losada; Lindsey R. Baden; Sharon E. Frey; Jennifer A. Whitaker; Susan J. Little; Evan J. Anderson; Emmanuel B. Walter; Richard M. Novak; Richard Rupp; Lisa A. Jackson; Tara M. Babu; Angelica C. Kottkamp; Anne F. Luetkemeyer; Lilly C. Immergluck; Rachel M. Presti; Martín Bäcker; Patricia L. Winokur; Siham M. Mahgoub; Paul A. Goepfert; Dahlene N. Fusco; Elissa Malkin; Jeffrey M. Bethony; Edward E. Walsh; Daniel S. Graciaa; Hady Samaha; Amy C. Sherman; Stephen R. Walsh; Getahun Abate; Zacharoula Oikonomopoulou; Hana M. El Sahly; Thomas C. S. Martin; Satoshi Kamidani; Michael J. Smith; Benjamin G. Ladner; Laura Porterfield; Maya Dunstan; Anna Wald; Tamia Davis; Robert L. Atmar; Mark J. Mulligan; Kirsten E. Lyke; Christine M. Posavad; Megan A. Meagher; David S. Stephens; Kathleen M. Neuzil; Kuleni Abebe; Heather Hill; Jim Albert; Kalyani Telu; Jinjian Mu; Teri C. Lewis; Lisa A. Giebeig; Amanda Eaton; Antonia Netzl; Samuel H. Wilks; Sina Türeli; Mamodikoe Makhene; Sonja Crandon; David C. Montefiori; Mat Makowski; Derek J. Smith; Seema U. Nayak; Paul C. Roberts; John H. Beigel; Patrick Kingsley; Kari Steinmetz; Michael Peasley; Cassie Grimsley Ackerley; Kristen E. Unterberger; Aimee Desrosiers; Marc Siegel; Alexandra Tong; Rebecca Rooks; Daniel F. Hoft; Irene Graham; Wendy A. Keitel; C. Mary Healy; Nicole Carter; Steven Hendrickx; Christina A. Rostad; Etza Peters; Lauren Nolan; M. Anthony Moody; Kenneth E. Schmader; Andrea Wendrow; Jessica Herrick; Rebecca Lau; Barbara Carste; Taylor Krause; Kirsten Hauge; Celia Engelson; Vijaya Soma; Chloe Harris; Azquena Munoz Lopez; Erica Johnson; Austin Chan; Fatima Ali; Trisha Parker; Jane A. O’Halloran; Ryley M. Thompson; Kimberly Byrnes; Asif Noor; Jeffery Meier; Jack Stapleton; Celia Maxwell; Sarah Shami; Arnaud C. Drouin; Florice K. Numbi; Julie McElrath; Mike Gale; Holly Baughman; Lisa McQuarrie; Theresa M. Engel; Caleb J. Griffith; Wendi L. McDonald; Alissa E. Burkey; Lisa B. Hoopengardner; Jessica E. Linton; Nikki L. Gettinger; Marina Lee; Mohamed Elsafy; Rhonda Pikaart-Tautges; Janice Arega; Binh Hoang; Dan Curtin; Hyung Koo; Elisa Sindall; Marciela M. DeGrace; Diane J. Post; Monica M. Farley; Jeanne Marrazzo; Sidnee Paschal Young; Jeffery Lennox; Linda McNeil; Elizabeth Brown; COVAIL Study Group

doi:10.1038/s41591-023-02503-4

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

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

Angela R. Branche, Nadine G. Rouphael, David J. Diemert, Ann R. Falsey, Cecilia Losada, Lindsey R. Baden, Sharon E. Frey, Jennifer A. Whitaker, Susan J. Little, Evan J. Anderson, …

Nature medicine, Vol.29(9), pp.2334-2346

09/2023

DOI: 10.1038/s41591-023-02503-4

PMCID: PMC10504073

PMID: 37640860

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Abstract

Abstract 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 .

Details

Title: Subtitle: Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
Creators: Angela R. Branche
Nadine G. Rouphael
David J. Diemert
Ann R. Falsey
Cecilia Losada
Lindsey R. Baden
Sharon E. Frey
Jennifer A. Whitaker
Susan J. Little
Evan J. Anderson
Emmanuel B. Walter
Richard M. Novak
Richard Rupp
Lisa A. Jackson
Tara M. Babu
Angelica C. Kottkamp
Anne F. Luetkemeyer
Lilly C. Immergluck
Rachel M. Presti
Martín Bäcker
Patricia L. Winokur
Siham M. Mahgoub
Paul A. Goepfert
Dahlene N. Fusco
Elissa Malkin
Jeffrey M. Bethony
Edward E. Walsh
Daniel S. Graciaa
Hady Samaha
Amy C. Sherman
Stephen R. Walsh
Getahun Abate
Zacharoula Oikonomopoulou
Hana M. El Sahly
Thomas C. S. Martin
Satoshi Kamidani
Michael J. Smith
Benjamin G. Ladner
Laura Porterfield
Maya Dunstan
Anna Wald
Tamia Davis
Robert L. Atmar
Mark J. Mulligan
Kirsten E. Lyke
Christine M. Posavad
Megan A. Meagher
David S. Stephens
Kathleen M. Neuzil
Kuleni Abebe
Heather Hill
Jim Albert - Emmes (United States)
Kalyani Telu
Jinjian Mu
Teri C. Lewis
Lisa A. Giebeig
Amanda Eaton
Antonia Netzl
Samuel H. Wilks
Sina Türeli
Mamodikoe Makhene
Sonja Crandon
David C. Montefiori
Mat Makowski
Derek J. Smith
Seema U. Nayak
Paul C. Roberts
John H. Beigel
Patrick Kingsley
Kari Steinmetz
Michael Peasley
Cassie Grimsley Ackerley
Kristen E. Unterberger
Aimee Desrosiers
Marc Siegel
Alexandra Tong
Rebecca Rooks
Daniel F. Hoft
Irene Graham
Wendy A. Keitel
C. Mary Healy
Nicole Carter
Steven Hendrickx
Christina A. Rostad
Etza Peters
Lauren Nolan
M. Anthony Moody
Kenneth E. Schmader
Andrea Wendrow
Jessica Herrick
Rebecca Lau
Barbara Carste
Taylor Krause
Kirsten Hauge
Celia Engelson
Vijaya Soma
Chloe Harris
Azquena Munoz Lopez
Erica Johnson
Austin Chan
Fatima Ali
Trisha Parker
Jane A. O’Halloran
Ryley M. Thompson
Kimberly Byrnes
Asif Noor
Jeffery Meier
Jack Stapleton
Celia Maxwell
Sarah Shami
Arnaud C. Drouin
Florice K. Numbi
Julie McElrath
Mike Gale
Holly Baughman
Lisa McQuarrie
Theresa M. Engel
Caleb J. Griffith
Wendi L. McDonald
Alissa E. Burkey
Lisa B. Hoopengardner
Jessica E. Linton
Nikki L. Gettinger
Marina Lee
Mohamed Elsafy
Rhonda Pikaart-Tautges
Janice Arega
Binh Hoang
Dan Curtin
Hyung Koo
Elisa Sindall
Marciela M. DeGrace
Diane J. Post
Kathleen M. Neuzil
Monica M. Farley
Jeanne Marrazzo
Sidnee Paschal Young
Jeffery Lennox
Linda McNeil
Elizabeth Brown
COVAIL Study Group
Resource Type: Journal article
Publication Details: Nature medicine, Vol.29(9), pp.2334-2346
DOI: 10.1038/s41591-023-02503-4
PMID: 37640860
PMCID: PMC10504073
NLM abbreviation: Nat Med
ISSN: 1078-8956
eISSN: 1546-170X
Grant note: DOI: 10.13039/100000054, name: U.S. Department of Health & Human Services | NIH | National Cancer Institute, award: Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007, Contract No. 75N91019D00024 Task Order No. 75N91022F00007
Language: English
Electronic publication date: 08/28/2023
Date published: 09/2023
Academic Unit: Microbiology and Immunology; Infectious Diseases; Epidemiology; Surgery; Radiation Oncology; Medicine Administration; Internal Medicine
Record Identifier: 9984459657202771

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