mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

Abstract

Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured the neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild-type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that received their primary series recently (<3 months), distantly (6–12 months), or an additional “booster” dose, while accounting for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinees. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron, only 4–6-fold lower than wild type, suggesting enhanced cross-reactivity of neutralizing antibody responses. In addition, we find that Omicron pseudovirus infects more efficiently than other variants tested. Overall, this study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.

Omicron variant showed lower neutralizing sensitivity than other SARS-CoV-2 variants to immune sera elicited by vaccines after boost

“…However, the good news is that more and more evidence exhibited that three doses of heterologous or homologous booster vaccination had a 25-100-fold-increase in neutralizing titres compared to two-dose vaccinations[ 6–8 ]. And the prior history of infection was associated with high levels of neutralization titres in vaccinated individuals[ 8 ].…”

Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein

“…This fitness advantage has been tentatively linked with a substantial ability to evade immunity from previous infection ( Pulliam et al, 2021 ), which might be consistent with the high number of non-synonymous mutations and indels observed in the S gene compared with the reference SARS-CoV-2 genome. These include a number of previously described RBD mutations associated with the aforementioned VOC, such as T478K and N501Y, plus E484A, which suggested significant immune evasion properties, later confirmed by a number of in vitro studies ( Cele et al, 2021 ; Garcia-Beltran et al, 2021 ; Schmidt et al, 2021 ; Willett et al, 2022 ). Based on early epidemiological data and on the growing number of imported cases reported abroad, on December 1 st , 2021 WHO included B.1.1.529 in the list of VOCs under the “omicron” designation.…”

“…This unusual pattern of mutations results in significant immune escape in vitro and in an enhanced reinfection potential in vivo ( Cele et al, 2021 ; Garcia-Beltran et al, 2021 ; Schmidt et al, 2021 ; Willett et al, 2022 ). Moreover, omicron displays an altered cellular tropism and cell entry mechanism, which depends on the acquisition of an enhanced ability to rely on the TMPRSS2-independent endosomal route ( Peacock et al, 2022 ; Willett et al, 2022 ).…”

Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability

“…The COVID-19 pandemic, resulting from the zoonotic infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to rage on, fueled by continuously evolving variants, which are making current licensed vaccines less effective (Araf et al, 2022;Doria-Rose et al, 2021;Edara et al, 2021;Garcia-Beltran et al, 2022;Liu et al, 2021). Vaccines capable of neutralizing all SARS-CoV-2 variants for the foreseeable future are of high interest.…”

“…Evolving SARS-CoV-2 variants, such as Delta and Omicron, evade these antibodies by mutations that reduce or knockout antibody binding, but maintain or even enhance infectivity (Garcia-Beltran et al, 2022;Liu et al, 2021;Sievers et al, 2022;Syed et al, 2022). Antibodies against most other regions on the spike are generally poorly neutralizing to non-neutralizing; several antibodies, however, such as antibody S2P6 (Pinto et al, 2021) have been reported to neutralize diverse strains of beta coronaviruses through recognition of a stem-helix supersite of vulnerability in the S2 subunit (Hsieh et al, 2021;Li et al, 2022;Sauer et al, 2021;Zhou et al, 2021).…”