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Master of Public Health

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

AUTHORS

Branche AR , Rouphael NG , Diemert DJ , Falsey AR , Losada C , Baden LR , Frey SE , Whitaker JA , Little SJ , Anderson EJ , Walter EB , Novak RM , Rupp R , Jackson LA , Babu TM , Kottkamp AC , Luetkemeyer AF , Immergluck LC , Presti RM , Bäcker M , Winokur PL , Mahgoub SM , Goepfert PA , Fusco DN , Malkin E , Bethony JM , Walsh EE , Graciaa DS , Samaha H , Sherman AC , Walsh SR , Abate G , Oikonomopoulou Z , El Sahly HM , Martin TCS , Rostad CA , Smith MJ , Ladner BG , Porterfield L , Dunstan M , Wald A , Davis T , Atmar RL , Mulligan MJ , Lyke KE , Posavad CM , Meagher MA , Stephens DS , Neuzil KM , Abebe K , Hill H , Albert J , Lewis TC , Giebeig LA , Eaton A , Netzl A , Wilks SH , Türeli S , Makhene M , Crandon S , Lee M , Nayak SU , Montefiori DC , Makowski M , Smith DJ , Roberts PC , Beigel JH , , . medRxiv : the preprint server for health sciences. 2022 7 15; ().

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 ) 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.

Clinicaltrialsgov: NCT05289037.

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