Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection

Abstract

The explosive spread of the Omicron SARS-CoV-2 variant underscores the importance of analyzing the cross-protection from previous non-Omicron infection. We developed a high-throughput neutralization assay for Omicron SARS-CoV-2 by engineering the Omicron spike gene into an mNeonGreen USA-WA1/2020 SARS-CoV-2 (isolated in January 2020). Using this assay, we determined the neutralization titers of patient sera collected at 1- or 6-months after infection with non-Omicron SARS-CoV-2. From 1- to 6-month post-infection, the neutralization titers against USA-WA1/2020 decreased from 601 to 142 (a 4.2-fold reduction), while the neutralization titers against Omicron-spike SARS-CoV-2 remained low at 38 and 32, respectively. Thus, at 1- and 6-months after non-Omicron SARS-CoV-2 infection, the neutralization titers against Omicron were 15.8- and 4.4-fold lower than those against USA-WA1/2020, respectively. The low cross-neutralization against Omicron from previous non-Omicron infection supports vaccination of formerly infected individuals to mitigate the health impact of the ongoing Omicron surge.

SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron

“…Nevertheless, Omicron neutralizing antibody titers rapidly increase after a third immunization (Liu et al, 2021;Planas et al, 2021;Schmidt et al, 2021;Sokal et al, 2021b), most likely due to the presence of memory B cells that recognized Omicron RBD, as observed here. Memory B cells may have important contributions in protective immunity by making anamnestic neutralizing antibody responses after infection (Cameroni et al, 2021;Carren ˜o et al, 2021;Cele et al, 2021;Doria-Rose et al, 2021;Gagne et al, 2021;Garcia-Beltran et al, 2021;Zou et al, 2021).…”

Efficient Neutralization of SARS-CoV-2 Omicron and Other VOCs by a Broad Spectrum Antibody 8G3

“…The mutation related changes greatly affects the transmissibility of the virus, the symptoms of infection, and host immune response [17][18][19] . In addition to general immune evasion from neutralizing antibodies, Omicron also broadly caused dramatic reduction in the protective efficacy of vaccines and sera [20][21][22] [22][23][24], which leads to a reduction in the options of responding to the SARS-CoV-2 pandemic and forces the generation of more passive prevention policies. Many neutralizing antibodies are disabled due to the large number of and widely scattered mutation sites in the N-terminal domain (NTD) and RBD region of the Omicron variant 23,24 .…”

SARS-CoV-2 Variants and Vaccination

“…The above studies were all performed on the same set of human sera collected 2 or 4 weeks after the administration of two doses of the Pfizer vaccine (Fig 2 ). Many other studies have also demonstrated that the neutralization titers of infected and vaccinated people are significantly lower against Omicron than the WT virus [17,18]. However, as described above, a third dose of the Pfizer vaccine increases the magnitude and breadth of neutralization, thus leading to robust neutrali zation against the Omicron variant [18,46,47].…”

“…In addition, Omicron can escape many monoclonal antibodies and evade vaccineelicited neutralization [1416]. Furthermore, infection with previ ous non Omicron variants does not appear to elicit robust neutralization against Omicron [17]. However, booster vac cination (e.g., a third dose of the Pfizer/BioNTech vaccine or a booster dose of the Moderna vaccine) elicits good neu tralization against Omicron [18], thus supporting a booster vaccination strategy.…”