to the Editor:
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, several new viral variants have emerged, making the virus more contagious. However, effective immune defense has not been observed, and vaccines have been effective. Recently, the B.126.96.36.1999 (Omicron) variant has been described, which the World Health Organization has classified as a variant of concern on November 26, 2021.1
The oomicron variant is characterized by a large number of mutations, with 26 to 32 changes in the spike(s) protein.2 Given that many of these mutations are in regions known to confer immunity, we studied whether serum samples were obtained from individuals who had been vaccinated against SARS-CoV-2 or Those who had recovered from SARS-CoV-2 infection (ie, convalescents) would be able to neutralize the omicron variant. The observation that the Omicron variant is more likely to cause reinfection than the previous variants suggests some level of immunity to escape.3
We took serum samples from people who were infected with the B.1.1.7 (alpha), B.1.351 (beta), or B.1.617.2 (delta) variants of SARS-CoV-2 and who received the mRNA-1273 vaccine. (SpikeVax, Moderna), the ChAdOx1-S vaccine (also known as ChAdOx1 nCoV-19; Vaxjeveria, AstraZeneca), or the BNT162b2 vaccine (Comirnaty, Pfizer-BioNTech) or had received heterozygous vaccination (ie , one dose each) with the ChAdOx1-S and BNT162b2 vaccines. For all serum samples, we determined the titers of neutralizing antibodies against alpha, beta, delta and omicron variants using a focus-forming assay with a previously described replication-competent SARS-CoV-2 virus.4 We also obtained serum samples from individuals who became infected and were subsequently vaccinated (convalescent-vaccinated) or vaccinated and subsequently had successful infection (vaccine-convalescent). We analyzed neutralizing antibody titers against Delta and Omicron variants in these samples.
A total of 10 participants were infected with the alpha version, 8 with the beta version, and 7 with the delta version. Ten participants had received two doses of mRNA-1273 vaccine, 10 ChAdOx1-S vaccine, and 20 BNT162b2 vaccine; 20 participants had received heterozygous vaccination with the ChAdOx1-S and BNT162b2 vaccines. In addition, 5 participants were infected and subsequently received one or two doses of BNT162b2 vaccine, and 5 were vaccinated with two doses of mRNA-1273, ChAdOx1-S, or BNT162b2 vaccine and subsequently He was successfully infected. The characteristics of the participants are shown in Tables S1 to S3 in the Supplementary Appendix available with the full text of this paper at NEJM.org.
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 Had. BNT162b2 vaccine (panel D) or the B.1.1.7 (alpha) variant (panel E), B.1.351 (beta) variant (panel F), or B.1.617.2 (delta) variant (panel G). Samples were analyzed for 50% neutralization titers (IC.)50) against alpha (blue), beta (orange), delta (purple), and omicron (red) variants. Bars represent the mean and symbol of 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. IC of serum samples from participants who became infected and were subsequently vaccinated (convalescent-vaccination; open bars) or who were vaccinated and subsequently had infection (vaccine-infection; shaded bars) was analyzed for.50 against Delta and Omicron variants (panel h). In the left part of panel H (convalescent-vaccination), open circles indicate participants who received one dose of BNT162B2 vaccine after infection, and closed circles who received two doses of BNT162B2 vaccine; On the right (vaccination-convalescent), closed circles indicate participants who were vaccinated with two doses of BNT162b2 vaccine prior to infection, stars those who were vaccinated with two doses of ChAdOx1-S vaccine and those people who had been vaccinated with two doses of the mRNA-1273 vaccine.
Serum samples from vaccinated individuals neutralized the Omicron type to a much smaller extent than any other type (alpha, beta, or delta) analyzed (figure 1 and Table S4). We found some cross-neutralization of the Omicron variant in samples obtained from individuals who received either homozygous BNT162b2 vaccination or heterozygous ChAdOx1-S-BNT162b2 vaccination, but not in samples from individuals who received homozygous ChAdOx1-S vaccination Was. We did not find neutralizing antibodies against type Omicron in serum samples obtained 4 to 6 months after receiving the second dose of mRNA-1273 vaccine. However, in this group, the interval between receipt of the second dose and sampling was longer than in the other vaccination-regimen groups, for which serum samples were obtained only 1 month after the second dose was received. We did not analyze serum samples from individuals who had received the third dose of the vaccine. Serum samples that were obtained from convalescent participants did not largely neutralize the Omicron variant, although cross-neutralization was observed against other variants. However, 9 out of 10 serum samples that were obtained from convalescent-vaccinated or vaccinated-convalescent participants were able to neutralize the Omicron variant, although to a lesser extent than the delta variant.
The Omicron variant has already become the dominant variant in many countries and is causing considerable illness and death, although possibly to a lesser extent than previous variants. Although receiving a third dose (booster) of the BNT162b2 vaccine may increase the level of cross-neutralizing antibodies in the Omicron variant,5 Based on the data from the current study, there is a need for rapid development of new, different types of vaccines.
Annika Rosler, M.Sc.
Lydia Rippler, MSc.
David Bunte, MD
Dorothy Von Laer, MD
Janine Kimpel, Ph.D.
Medical University of Innsbruck, Innsbruck, Austria
Disclosure forms provided by the authors are available along with the full text of this letter at NEJM.org.
This letter was published on NEJM.org on January 12, 2022.
1. World Health Organization. Omicron’s Classification (B.1.1.529): SARS-CoV-2 Concern. November 26, 2021 (https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern).
2. Network for Genomic Surveillance in South Africa (NGS-SA). SARS-CoV-2 sequencing update. November 26, 2021 (https://www.nicd.ac.za/wp-content/uploads/2021/11/Update-of-SA-sequencing-data-from-GISAID-26-Nov_Final.pdf).
3. Pulliaman JRC, Van Schalwick C, Govind Na, and others. The risk of re-infection of SARS-CoV-2 is associated with the emergence of the Omicron variant in South Africa. December 2, 2021 (https://www.medrxiv.org/content/10.1101/2021.11.11.21266068v2). preprint
4. rippler, rosler A, Proud, and others. Comparison of four SARS-CoV-2 neutralization assays. Vaccines (Basel) 2020;9:13,13,
5. Careno JM, Alshamri H, tcheu ju, and others. Activity of convalescent and vaccine serum against the SARS-CoV-2 omicron. Nature (in press) (https://www.nature.com/articles/d41586-021-03846-z).