SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection
Author:
Cele Sandile, Jackson Laurelle, Khoury David S., Khan Khadija, Moyo-Gwete Thandeka, Tegally Houriiyah, San James Emmanuel, Cromer Deborah, Scheepers Cathrine, Amoako Daniel, Karim Farina, Bernstein Mallory, Lustig Gila, Archary Derseree, Smith Muneerah, Ganga Yashica, Jule Zesuliwe, Reedoy Kajal, Hwa Shi-Hsia, Giandhari Jennifer, Blackburn Jonathan M., Gosnell Bernadett I., Karim Salim S. Abdool, Hanekom Willem, von Gottberg Anne, Bhiman Jinal, Lessells Richard J., Moosa Mahomed-Yunus S., Davenport Miles P.ORCID, de Oliveira TulioORCID, Moore Penny L.ORCID, Sigal AlexORCID, ,
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.
Publisher
Cold Spring Harbor Laboratory
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