mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

The Omicron (B.1.1.529) variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies4. This concern is amplified by the findings from our study. We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 18 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients. In addition, we also identified four new spike mutations (S371L, N440K, G446S, and Q493R) that confer greater antibody resistance to B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.

show abstract

“…Vaccines that elicited lower neutralizing titers 35,36 are expected to fare worse against B.1.1.529.…”

Section: Discussionmentioning

confidence: 99%

Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2

Liu

Iketani

Guo

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Using an analysis that synthesizes recent neutralization results with prior experiments to correlate vaccine efficacy against infection (35,36), we can infer the relative reduction in protection due to BA.1 versus Delta, which we presume is the primary circulating variant in the background transmission.…”

Section: Estimating the Plausible Range For Immune Escapementioning

confidence: 99%

Bounding the levels of transmissibility & immune evasion of the Omicron variant in South Africa

Pearson

Silal

et al. 2021

Preprint

View full text Add to dashboard Cite

A new SARS-CoV-2 variant of concern, Omicron (B.1.1.529), has been identified based on genomic sequencing and epidemiological data in South Africa. Presumptive Omicron cases in South Africa have grown extremely rapidly, despite high prior exposure and moderate vaccination coverage. The available evidence suggests that Omicron spread is at least in part due to evasion of this immune protection, though it may also exhibit higher intrinsic transmissibility. Using detailed laboratory and epidemiological data from South Africa, we estimate the constraints on these two characteristics of the new variant and their relationship. Our estimates and associated uncertainties provide essential information to inform projection and scenario modeling analyses, which are crucial planning tools for governments around the world.

show abstract

“…Among the variants that have emerged so far, Beta and Omicron variants have a greater ability to escape from neutralizing antibodies than Alpha and Delta variants, that are dominantly circulated in the past ( 11 ). In particular, the Omicron variant drastically reduced the neutralizing activity of circulating antibodies in fully vaccinated individuals and many therapeutic monoclonal antibodies in clinical use ( 12–16 ). Epidemiological evidence further suggest a reduction in the vaccine effectiveness against this variant ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

“…Despite the antigenic alteration in the variants, the third dose of mRNA vaccines recalls the cross-neutralizing antibodies that are more resistant to Beta and Omicron variants than the antibodies elicited after the second vaccine dose ( 16, 18, 19 ). One possible explanation for this phenomenon is that the B mem cells induced after the second vaccine dose are more cross-reactive against the variants than the circulating antibodies from plasma cells.…”

Section: Introductionmentioning

confidence: 99%

Two doses of mRNA vaccine elicit cross-neutralizing memory B-cells against SARS-CoV-2 Omicron variant

Kotaki

Adachi

Moriyama

et al. 2021

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 Beta and Omicron variants have multiple mutations in the receptor-binding domain (RBD) allowing antibody evasion. Despite the resistance to circulating antibodies in those who received two doses of mRNA vaccine, the third dose prominently recalls cross-neutralizing antibodies with expanded breadth to these variants. Herein, we longitudinally profiled the cellular composition of persistent memory B-cell subsets and their antibody reactivity against these variants following the second vaccine dose. The vaccination elicited a memory B-cell subset with resting phenotype that dominated the other subsets at 4.9 months. Notably, most of the resting memory subset retained the ability to bind the Beta variant, and the memory-derived antibodies cross-neutralized the Beta and Omicron variants at frequencies of 59% and 29%, respectively. The preservation of cross-neutralizing antibody repertoires in the durable memory B-cell subset likely contributes to the prominent recall of cross-neutralizing antibodies following the third dose of the vaccine.

show abstract

mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

Cited by 112 publications

References 44 publications

Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2

Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2

Bounding the levels of transmissibility & immune evasion of the Omicron variant in South Africa

Two doses of mRNA vaccine elicit cross-neutralizing memory B-cells against SARS-CoV-2 Omicron variant

Contact Info

Product

Resources

About