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. 2022 Jan 24;3(2):100529.
doi: 10.1016/j.xcrm.2022.100529. eCollection 2022 Feb 15.

mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 omicron variant

Venkata-Viswanadh Edara  1   2   3 , Kelly E Manning  1   2   3 , Madison Ellis  1   2   3 , Lilin Lai  1   2   3 , Kathryn M Moore  1   2   3 , Stephanie L Foster  1   2   3 , Katharine Floyd  1   2   3 , Meredith E Davis-Gardner  1   2   3 , Grace Mantus  1   2   4 , Lindsay E Nyhoff  1   2   4 , Sarah Bechnak  4 , Ghina Alaaeddine  4 , Amal Naji  4 , Hady Samaha  4 , Matthew Lee  4 , Laurel Bristow  4 , Matthew Gagne  5 , Jesmine Roberts-Torres  5 , Amy R Henry  5 , Sucheta Godbole  5 , Arash Grakoui  2   6   4   3 , Marybeth Saxton  4 , Anne Piantadosi  4   7 , Jesse J Waggoner  4 , Daniel C Douek  5 , Nadine Rouphael  4   8 , Jens Wrammert  1   2 , Mehul S Suthar  1   2   6   3
Affiliations

mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 omicron variant

Venkata-Viswanadh Edara et al. Cell Rep Med. .

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant emerged in November 2021 and consists of several mutations within the spike. We use serum from mRNA-vaccinated individuals to measure neutralization activity against omicron in a live-virus assay. At 2-4 weeks after a primary series of vaccinations, we observe a 30-fold reduction in neutralizing activity against omicron. Six months after the initial two-vaccine doses, sera from naive vaccinated subjects show no neutralizing activity against omicron. In contrast, COVID-19-recovered individuals 6 months after receiving the primary series of vaccinations show a 22-fold reduction, with the majority of the subjects retaining neutralizing antibody responses. In naive individuals following a booster shot (third dose), we observe a 14-fold reduction in neutralizing activity against omicron, and over 90% of subjects show neutralizing activity. These findings show that a third dose is required to provide robust neutralizing antibody responses against the omicron variant.

Keywords: B.1.1.529; Omicron; Omicron variant; SARS-CoV-2; antibody; booster dose; live-virus; mRNA vaccines; neutralization assay; vaccine induced immunity.

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Conflict of interest statement

M.S.S. serves on the advisory board for Moderna and Ocugen.

Figures

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Graphical abstract
Figure 1
Figure 1
Neutralization antibody responses against WA1/2020, B.1.351, and B.1.1.529 SARS-CoV-2 variants post-mRNA vaccination (A–D) Data from the following cohorts are shown: (A) naive individuals 2–4 weeks after the second dose (n = 24), (B) naive individuals 6 months after the second dose (n = 25), (C) recovered individuals who received the primary mRNA vaccination series (n = 37), and (D) naive vaccinated individuals who received a third dose (n = 52). In (A)–(D), the FRNT50 GMTs for WA1/2020, B.1.351, and B.1.1.529 are shown with respective fold changes in comparison with the WA1/2020. A pie chart above each graph shows the frequency of individuals who have titers above (Responders) or below (Non-responders) the limit of detection (LOD). The connecting lines between the variants represent matched serum samples. The horizontal dashed lines along the x axis indicate the LOD (FRNT50 GMT = 10). Blue circles represent individuals who received the Moderna mRNA-1273 vaccine as the primary vaccine series, and the red circles represent individuals who received the Pfizer-BioNTech BNT162b2 vaccine as the primary vaccine series. Normality of the data was determined using Shapiro-Wilk normality test. Non-parametric pairwise analysis for neutralization titers was performed by Wilcoxon matched pairs signed rank test. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001.
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