key: cord-0889025-la6sd0i4
authors: Edara, Venkata-Viswanadh; Manning, Kelly E.; Ellis, Madison; Lai, Lilin; Moore, Kathryn M.; Foster, Stephanie L.; Floyd, Katharine; Davis-Gardner, Meredith E.; Mantus, Grace; Nyhoff, Lindsay E.; Bechnak, Sarah; Alaaeddine, Ghina; Naji, Amal; Samaha, Hady; Lee, Matthew; Bristow, Laurel; Gagne, Matthew; Roberts-Torres, Jesmine; Henry, Amy R.; Godbole, Sucheta; Grakoui, Arash; Saxton, Marybeth; Piantadosi, Anne; Waggoner, Jesse J.; Douek, Daniel C.; Rouphael, Nadine; Wrammert, Jens; Suthar, Mehul S.
title: mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant
date: 2022-01-24
journal: Cell Rep Med
DOI: 10.1016/j.xcrm.2022.100529
sha: 6af367c444783340beab9400e9b991c5f30999d2
doc_id: 889025
cord_uid: la6sd0i4

The SARS-CoV-2 omicron variant emerged in November 2021 and consists of several mutations within the spike. We used serum from mRNA vaccinated individuals to measure neutralization activity against omicron in a live-virus assay. Following 2-4 weeks after primary series of vaccinations, we observed a 30-fold reduction in neutralizing activity against Omicron. Six months after the initial two vaccine doses, sera from naïve vaccinated subjects showed no neutralizing activity against omicron. In contrast, COVID-19 recovered individuals six months after receiving the primary series of vaccinations show a 22-fold reduction with majority of the subjects retaining neutralizing antibody responses. In naïve individuals following a booster shot (3rd dose), we observed a 14-fold reduction in neutralizing activity against omicron and over 90% of subjects show neutralizing activity. These findings show that a 3rd dose is required to provide robust neutralizing antibody responses against the omicron variant.

The SARS-CoV-2 omicron variant emerged in November 2021 and consists of several mutations 26 within the spike. We used serum from mRNA vaccinated individuals to measure neutralization 27 activity against omicron in a live-virus assay. Following 2-4 weeks after primary series of 28 vaccinations, we observed a 30-fold reduction in neutralizing activity against Omicron. Six months 29 after the initial two vaccine doses, sera from naïve vaccinated subjects showed no neutralizing 30 activity against omicron. In contrast, COVID-19 recovered individuals six months after receiving 31 the primary series of vaccinations show a 22-fold reduction with majority of the subjects retaining 32 neutralizing antibody responses. In naïve individuals following a booster shot (3rd dose), we 33

The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines generate potent and 38 durable neutralizing antibody responses against the severe acute respiratory syndrome coronavirus 39 2 (SARS-CoV-2) 1-3 . The global emergence of SARS-CoV-2 variants with mutations in the spike 40 protein, the principal antigenic target of these vaccines, has raised concern regarding the 41 effectiveness of these vaccines. We previously found that mRNA vaccine-induced antibody 42 responses have reduced neutralizing activity against the B. (A67V, Δ69-70, T95I, G142D, Δ143-145, Δ211, N211I,  49   +214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A,  50   Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K,  51   D796Y, N856K, Q954H, N969K, L981F) (Fig. 1a) . Further, only 21% of the subjects show neutralizing antibody titers against 68 the B.1.1.529 variant. Individuals that do not neutralize at the limit of detection at 50% are plotted 69 at 10 and was used for geometric mean and fold-change calculations and these samples are 70 considered as undetectable or non-responders against the respective variant. 71 72 Next, we examined the durability of neutralizing antibody responses in vaccinated subjects 6 73 months after receiving the 2nd dose. This cohort was divided between individuals with no known 74 prior COVID-19 exposure and those that had recovered from COVID-19 and then received the 75 Moderna or Pfizer vaccine. In naïve vaccinated subjects, the GMTs at 6 months are 53 for WA1, 76 23 for B.1.351, and <20 for B.1.1.529 (Fig. 1b) . This corresponds to a 2.3-fold reduction against 77 B.1.351 as compared to WA1, however, none of these subjects show any detectable neutralizing 78 activity against the B.1.1.529 variant. In recovered individuals that received the vaccine, the GMTs 79 are 719 for WA1, 366 for B.1.351 and 33 for B.1.1.529 and corresponds to a 2-and 22-fold 80 reduction as compared to WA1, respectively (Fig. 1c) . In contrast to naïve vaccinated subjects, 81 months after the 2nd dose. 

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