Health

SARS-CoV-2 Omicron Variant Neutralization in Serum of Vaccinated and Recovered Persons

To the editor:

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, several new viral variants emerged, causing the virus to become more contagious. However, effective immune escape was not observed, and vaccines remained effective. Recently, the B.1.1.529 (omicron) variant, which was classified by the World Health Organization as a variant of concern on November 26, 2021, was described.1

The omicron variant is characterized by a large number of mutations, with 26 to 32 changes in the spike (S) protein.2 Since many of these mutations are located in regions known to be involved in immune escape, we examined whether serum samples obtained from subjects who had been vaccinated against SARS-CoV-2 or who had recovered from SARS-CoV-2 infection (ie ., convalescence) able to neutralize the omicron variable. The observation that the omicron variant was more likely to cause re-infection than the previous variants indicates a certain level of immune escape.3

We obtained serum samples from subjects infected with the B.1.1.7 (alpha), B.1.351 (beta), or B.1.617.2 (delta) variant of SARS-CoV-2 and from subjects who received two doses of mRNA vaccine -1273 (Spikevax, Moderna), ChAdOx1-S vaccine (also known as ChAdOx1 nCoV-19; Vaxzevria, AstraZeneca), BNT162b2 (Comirnaty, Pfizer – BioNTech) vaccine or heterogeneous vaccine any single dose each) with ChAdOx1-S vaccine and BNT162b2. For all serum samples, we determined neutralizing antibody titers against alpha, beta, delta and omicron variants using a focus-forming assay with replication-competent SARS-CoV-2 viruses, as previously described.4 We also obtained serum samples from people who became infected and were subsequently vaccinated (convalescent-vaccine) or vaccinated and subsequently had a breakthrough infection (vaccine-convalescent). We analyzed neutralization antibody titer against delta and omicron variables in these samples.

A total of 10 participants infected with the alpha variant, 8 infected with the beta variant, and 7 infected with the delta variant. Ten participants received two doses of the mRNA-1273 vaccine, 10 of the ChAdOx1-S vaccine, and 20 of the BNT162b2 vaccine; 20 participants received a heterozygous vaccine with ChAdOx1-S and BNT162b2 vaccines. In addition, 5 participants were infected and subsequently received 1 or 2 doses of BNT162b2 vaccine, and 5 participants were vaccinated with 2 doses of mRNA-1273, ChAdOx1-S or BNT162b2 vaccine and then developed a breakthrough infection. Participant characteristics in Tables S1 through S3 are presented in the Supplementary Appendix, available with the full text of this letter at NEJM.org.

Neutralization of the variable B.1.1.529 (Omicron) in comparison with the other variables of interest.

Serum samples were obtained from participants who received two doses of mRNA-1273 vaccine (panel A), two doses of ChAdOx1-S vaccine (panel B), heterozygous ChAdOx1-S-BNT162b2 vaccination (panel C), or two doses of BNT162b2 vaccine (panel C). (panel D) or who have recovered from infection (ie, convalescent) with the B.1.1.7 (alpha) variant (panel E), the B.1.351 (beta) variant (panel F), or the B.1.617.2 (delta) variant Alt (panel G). Samples were analyzed for 50% equivalent titers (IC .).50) versus alpha (blue), beta (orange), delta (purple), and omicron (red) variables. Bars indicate means and symbols for individual serum samples. Samples from the same participant are connected by lines. The dashed line in each panel indicates the detection limit. Numbers in panels A to G indicate the proportion of serum samples that were positive (>1:16) for the omicron variant. Serum samples from participants who were infected and subsequently vaccinated (convalescent vaccine, open bars) or who were vaccinated and subsequently had a breakthrough infection (convalescent vaccine; shaded bars) were analyzed for interstitial cystitis50 vs delta and omicron variables (panel H). In the left part of panel H (convalescence – vaccination), open circles indicate participants who received one dose of BNT162b2 vaccine after infection, and closed circles those who received two doses of BNT162b2 vaccine; In the right pane (vaccination – convalescence), closed circles indicate participants who were vaccinated with two doses of BNT162b2 vaccine prior to infection, stars of those vaccinated with two doses of ChAdOx1-S vaccine, and the square of those vaccinated with two doses of mRNA-1273 vaccine.

Serum samples from vaccinated subjects neutralized the omicron variable to a much lower degree than any other analyzed variable (alpha, beta or delta) (shape 1 and Table S4). We found some cross-neutralization of the omicron variant in samples obtained from subjects who received either the homozygous BNT162b2 vaccination or the heterozygous ChAdOx1-S-BNT162b2 vaccination but not in samples from subjects who received the homozygous ChAdOx1-S vaccine. We did not find neutralizing antibodies to the omicron variant in serum samples obtained 4–6 months after receiving the second dose of mRNA-1273 vaccine. However, in this group, the interval between receiving the second dose and sampling was longer than in the other vaccination regimen groups, as serum samples were obtained only 1 month after receiving the second dose. We did not analyze serum samples from subjects who received a third dose of the vaccine. Serum samples obtained from convalescent participants did not significantly neutralize the omicron variable, although cross-neutralization against other variables was observed. However, 9 of the 10 serum samples obtained from convalescent participants—vaccinated or vaccinated—were able to neutralize the omicron variable, albeit to a lesser degree than the delta variable.

The omicron variant has already become the dominant variant in many countries and causes significant disease and death, although perhaps to a somewhat lesser degree than previous variants. Although receiving a third (booster) dose of BNT162b2 vaccine may increase the level of omicron-neutralizing cross-antibody,5 On the basis of the data in the current study, the rapid development of new, variant vaccines is warranted.

Annika Rossler, MA
Lydia Rippler, MA
David Panty, MD
Dorothy Von Laer, MD
Janine Kimball, Ph.D.
Medical University of Innsbruck, Innsbruck, Austria
[email protected]

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This message was originally published on January 12, 2022 at NEJM.org.

  1. 1. World Health Organization. Omicron classification (B 1.1.529): A SARS-CoV-2 variant of concern. November 26And 2021 (https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern).

  2. 2. South African Genomic Surveillance Network (NGS-SA). SARS-CoV-2 sequence update. November 26And 2021 (https://www.nicd.ac.za/wp-content/uploads/2021/11/Update-of-SA-sequencing-data-from-GISAID-26-Nov_Final.pdf).

  3. 3. Pulliamn JRCAnd Van Schalkwyk SeeAnd Govender, and others. Increased risk of reinfection with SARS-CoV-2 associated with the emergence of the omicron variant in South Africa. December 2And 2021 (https://www.medrxiv.org/content/10.1101/2021.11.11.21266068v2). pre-print.

  4. 4. Repler LAnd Rossler AAnd Proud of, and others. Comparison of four SARS-CoV-2 neutralization assays. Vaccines (Basel) 2020; 9:1313.

  5. 5. Carino JimAnd Al-Shammari hAnd Qiu Ji, and others. Activity of convalescent serum and vaccine against SARS-CoV-2 Umicron. Nature (in press) (https://www.nature.com/articles/d41586-021-03846-z).

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