SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection

Abstract

The emergence of SARS-CoV-2 Omicron, first identified in Botswana and South Africa, may compromise vaccine effectiveness and the ability of antibodies triggered by previous infection to protect against re-infection (1). Here we investigated whether Omicron escapes antibody neutralization in South Africans, either previously SARS-CoV-2 infected or uninfected, who were vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa and compared plasma neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation, observing that Omicron still required ACE2 to infect. For neutralization, blood samples were taken soon after vaccination, so that vaccine elicited neutralization was close to peak. Neutralization capacity of the D614G virus was much higher in infected and vaccinated versus vaccinated only participants but both groups had 22-fold Omicron escape from vaccine elicited neutralization. Previously infected and vaccinated individuals had residual neutralization predicted to confer 73% protection from symptomatic Omicron infection, while those without previous infection were predicted to retain only about 35%. Both groups were predicted to have substantial protection from severe disease. These data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly boosting, could maintain reasonable effectiveness against Omicron. A waning neutralization response is likely to decrease vaccine effectiveness below these estimates. However, since protection from severe disease requires lower neutralization levels and involves T cell immunity, such protection may be maintained.

Figure 1:. ACE2 dependence and neutralization of the Omicron variant by Pfizer BNT162b2 elicited immunity

(A) Images of infection foci in titration of live SARS-CoV-2 Omicron virus on H1299-ACE2 and H1299 parental cells. Numbers above well images denote viral stock dilution. Scale bar is 2mm. (B) Quantified number of foci as a function of Omicron virus stock dilution. Mean and standard deviation of 6 replicates from 2 independent experiments. (C) Neutralization of Omicron virus compared to D614G ancestral virus by plasma from participants vaccinated with BNT162b2 and previously SARS-CoV-2 infected (green) or vaccinated only (orange). Numbers in black above each virus strain are geometric mean titers (GMT) of the reciprocal plasma dilution (FRNT50) resulting in 50% reduction in the number of infection foci. Red horizontal line denotes most concentrated plasma used. 21 samples were tested from 19 participants in 2 independent experiments, where n=6 were vaccinated only and n=13 were vaccinated and previously infected. p=4.8 × 10⁻⁵ as determined by the Wilcoxon rank sum test. (D) Geometric means and 95% confidence intervals of fold-changes between participant FRNT50 values for ancestral D614G versus Omicron neutralization. Purple denotes all participants, green denotes vaccinated previously infected and orange denotes vaccinated only. (E) Prediction of vaccine efficacy against symptomatic infection (left) and severe disease (right) based on Omicron neutralization results.