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[Preprint]. 2022 Jul 15:2022.07.12.22277336. [Version 1] doi: 10.1101/2022.07.12.22277336

SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses

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 CS Martin, Christina A Rostad, 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, Teri C Lewis, Lisa A Giebeig, Amanda Eaton, Antonia Netzl, Samuel H Wilks, Sina Türeli, Mamodikoe Makhene, Sonja Crandon, Marina Lee, Seema U Nayak, David C Montefiori, Mat Makowski, Derek J Smith, Paul C Roberts, John H Beigel; the COVAIL Study Group
PMCID: PMC9327623  PMID: 35898343

ABSTRACT

Background

Protection 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.

Methods

This 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 (ID 50 ) 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.

Results

From 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).

Conclusions

Higher 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.gov

NCT05289037

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.

Articles from medRxiv are provided here courtesy of Cold Spring Harbor Laboratory Preprints

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