Immune Neutralization of Omicron

December 2021 marked the two-year anniversary of COVID-19 emerging [1] – a milestone that many did not anticipate. Yet even now, with over 320 million infections reported globally [2], “herd immunity” is a phrase repeated with less and less frequency. Currently, 76 countries are experiencing yet another rise in COVID-19 infections [3]. The majority of these cases can be attributed to the omicron variant, and current data suggests that immune neutralization of this variant may be weaker compared to other variants.

Scientists suspect that omicron’s ability to spread even in previously infected and vaccinated populations can be attributed to some degree of “immune evasion.” Antibodies from a previous infection, or even from the vaccine, might not be able to recognize the new version of the virus, which has an estimated 26 to 32 mutations in the S protein [4]. Therefore, the immune system must adapt all over again when learning to recognize and suppress omicron, decreasing the likelihood of neutralization.

Given that there are not yet vaccines which target the more novel variants of COVID-19, the question remains as to which antibodies confer the greatest immune neutralization of omicron. A small-scale study, published as a letter in the New England Journal of Medicine in January of 2022 [5], may provide preliminary answers.

Rössler et al. wrote from the Medical University of Innsbruck, of Innsbruck, Austria, where they had taken serum samples from patients previously infected with the alpha (n=10), beta (n=8), or delta (n=7) variants of the virus. They also obtained samples from patients who had received two doses of the Moderna (n=10), AstraZeneca (n=10), and Pfizer-BioNTech vaccine (n=20), as well as those who received one dose each of the AstraZeneca and Pfizer-BioNTech vaccine (n=20). Finally, patients who had been previously vaccinated but had experienced a breakthrough infection (n=5), as well as patients who were previously infected before getting vaccinated (n=5), were also included in the study population [5].

The authors used the obtained serum samples from each patient population to analyze neutralizing antibody titers against both the delta and omicron variants. As expected, serum samples from vaccinated patients neutralized the omicron variant far less effectively than the delta variant, supporting the immune evasion hypothesis. Cross-neutralization of the omicron variant was observed in serum samples of patients vaccinated with the Pfizer-BioNTech vaccine as well as in patients who received both the AstraZeneca and Pfizer-BioNTech vaccine. On the other hand, homologous AstraZeneca vaccine doses and Moderna vaccine doses (4-6 months after injection) were associated with little to no omicron neutralization. The same was true of patients infected with the other strains of the virus, although neutralizing antibody titers against the delta variant were detected in their serum samples. Interestingly, ninety percent of serum samples from patients who had a history of vaccination and infection were able to neutralize the omicron variant, suggesting that a more diverse antibody population confers improved protection against omicron. Each serum type was consistently more effective at neutralizing the delta variant when compared to the omicron variant.

Overall, Rössler et al. concluded that the most prominent types of antibody-conferred protection against COVID-19 failed to effectively and consistently neutralize the omicron variant. There is a need for an “updated” vaccine to better control the omicron variant and possible future variants. While their study was limited in scale and will need to be replicated, their findings are consistent with the larger epidemiological trends that have been observed on a global scale.

References 

1 Katella, K. (2021, March 9). Our pandemic year-A covid-19 timeline. Yale Medicine. Retrieved from https://www.yalemedicine.org/news/covid-timeline 

2 Coronavirus Cases:. (2021). Retrieved from https://www.worldometers.info/coronavirus/ 

3 Bhatia, G., Dutta, P. K., & McClure, J. (2022, January 26). Covid-19: The Latest Global Statistics, charts and maps. Reuters. Retrieved from https://graphics.reuters.com/world-coronavirus-tracker-and-maps/

4 SARS-COV-2 sequencing update 12 November – nicd.ac.za. (2021). Retrieved from https://www.nicd.ac.za/wp-content/uploads/2021/11/Update-of-SA-sequencing-data-from-GISAID-12-Nov_Final.pdf 

5 Rössler, A., Riepler, L., Bante, D., von Laer, D., & Kimpel, J. (2022). SARS-CoV-2 Omicron Variant Neutralization in Serum from Vaccinated and Convalescent Persons. The New England journal of medicine, NEJMc2119236. Advance online publication. doi:10.1056/NEJMc2119236