Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis

Angela Choi,Jacqueline M Miller,Lingzhi Ma,Holly Legault,Matthew Koch,Brett Leav,Naveen Nunna,Rolando Pajón ,Kai Wu,Hamilton Bennett,A V Hill ,Yamuna Devi Paila ,Tonya M Colpitts ,Wenmei Huang,Laurence Chu,Baoyu Ding,Judy Oestreicher,Biliana Nestorova,David C Montefiori ,Andrea Carfı́ ,Roderick Mcphee,Darin K Edwards

doi:10.1038/s41591-021-01527-y

Abstract

The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines. Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study (NCT04405076) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. As the trial is currently ongoing, this exploratory interim analysis includes preliminary descriptive results only of four booster groups (n = 20 per group). Immediately before the booster dose, neutralizing antibodies against wild-type D614G virus had waned (P < 0.0001) relative to peak titers against wild-type D614G measured 1 month after the primary series, and neutralization titers against B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) VOCs were either low or undetectable. Both the mRNA-1273 booster and variant-modified boosters were safe and well-tolerated. All boosters, including mRNA-1273, numerically increased neutralization titers against the wild-type D614G virus compared to peak titers against wild-type D614G measured 1 month after the primary series; significant increases were observed for mRNA-1273 and mRNA-1273.211 (P < 0.0001). In addition, all boosters increased neutralization titers against key VOCs and VOIs, including B.1.351, P.1. and B.1.617.2, that were statistically equivalent to peak titers measured after the primary vaccine series against wild-type D614G virus, with superior titers against some VOIs. This trial is ongoing.

Highlights

The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines
SARS-CoV-2 vaccines, such as mRNA-1273, are highly effective in reducing detectable symptomatic infections and severe complications of Coronavirus Disease 2019 (COVID-19)[5], several viral variants with changes in the S protein have emerged, some of which have been identified as VOCs (Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2))[9,10,11]
The neutralizing capacity of sera collected from participants 7 d after completion of the mRNA-1273 primary series against VOCs17,18 was assessed using a previously described research grade vesicular stomatitis virus (VSV)-based SARS-CoV-2 pseudovirus neutralization (PsVN) assay[19]

Summary

Results

Neutralizing antibody titers against the wild-type D614G virus were measured with the VSV-based PsVN assay using samples collected 2 weeks after the booster dose and were compared against wild-type D614G GMT benchmarks from samples collected 1 month after the primary series vaccination in each group. These benchmarks were used to determine whether the boosters reached the same neutralization level shown in the pivotal study where efficacy was demonstrated (that is, levels seen for wild-type D614G where 94% efficacy was measured)[5].

Discussion

D15 D29

Methods