SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses
Authors: 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. , Rostad Christina A. , 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 , Lewis Teri C. , Giebeig Lisa A. , Eaton Amanda , Netzl Antonia , Wilks Samuel H. , Türeli Sina , Makhene Mamodikoe , Crandon Sonja , Lee Marina , Nayak Seema U. , Montefiori David C. , Makowski Mat , Smith Derek J. , Roberts Paul C. , Beigel John H. ,   the COVAIL Study Group
Published: July 2022

ABSTRACTBackgroundProtection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines.MethodsThis phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID50) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination.ResultsFrom March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907).ConclusionsHigher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines.Clinicaltrials.govNCT05289037