Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines

Bowen, John E.; Sprouse, Kaitlin R.; Walls, Alexandra C.; Mazzitelli, Ignacio; Logue, Jennifer; Franko, Nicholas; Ahmed, Kumail; Shariq, Asefa; Cameroni, Elisabetta; Gori, Andrea; Bori, Alessandra; Posavad, Christine M.; Dan, Jennifer M.; Zhang, Zeli; Weiskopf, Daniela; Sette, Alessandro; Crotty, Shane; Iqbal, Najeeha Talat; Corti, Davide; Geffner, Jorge; Grifantini, Renata; Veesler, David

doi:10.1101/2022.03.15.484542

Cited by 35 publications

(39 citation statements)

References 75 publications

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“…Vaccinated individuals infected with BA.1 can induce cross-reactive immunity to BA.2, and reinfection with BA.2 after BA.1 infection is rare ( 12–14 ). Protective efficacy by the first-generation vaccines against symptomatic COVID-19 after booster is also similar for BA.1 and BA.2 ( 15, 16 ). It remains important to understand the molecular characteristics of the BA.2 subvariant for developing effective intervention strategies.…”

Section: Introductionmentioning

confidence: 76%

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Structural and functional characteristics of SARS-CoV-2 Omicron subvariant BA.2 spike

Zhang

Tang

Gao

et al. 2022

Preprint

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The Omicron subvariant BA.2 has become the dominant circulating strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in many countries. We have characterized structural, functional and antigenic properties of the full-length BA.2 spike (S) protein and compared replication of the authentic virus in cell culture and animal model with previously prevalent variants. BA.2 S can fuse membranes more efficiently than Omicron BA.1, mainly due to lack of a BA.1-specific mutation that may retard the receptor engagement, but still less efficiently than other variants. Both BA.1 and BA.2 viruses replicated substantially faster in animal lungs than the early G614 (B.1) strain in the absence of pre-existing immunity, possibly explaining the increased transmissibility despite their functionally compromised spikes. As in BA.1, mutations in the BA.2 S remodel its antigenic surfaces leading to strong resistance to neutralizing antibodies. These results suggest that both immune evasion and replicative advantage may contribute to the heightened transmissibility for the Omicron subvariants.

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Section: Introductionmentioning

confidence: 76%

“…Protective efficacy by the first-generation vaccines against symptomatic COVID-19 after booster is also similar for BA.1 and BA.2 (15,16). It remains important to understand the molecular characteristics of the BA.2 subvariant for developing effective intervention strategies.…”

Section: Introductionmentioning

confidence: 99%

Structural and functional characteristics of SARS-CoV-2 Omicron subvariant BA.2 spike

Zhang

Tang

Gao

et al. 2022

Preprint

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“…A booster immunization or hybrid immunity strongly enhances neutralizing antibodies against both omicron variants. 11-13 However, these studies mainly analyzed samples from vaccinated individuals and little is known about neutralizing antibody profiles induced by BA.2 omicron infection in previously naïve individuals.…”

Section: Introductionmentioning

confidence: 99%

BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants

Rössler

Netzl

Knabl³

et al. 2022

Preprint

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BackgroundSeveral studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant and current vaccines and infection with pre-omicron variants provide limited protection against BA.1. Meanwhile, however, omicron BA.2 has become the dominant variant in many countries and has replaced BA.1. As BA.2 has several mutations especially in the receptor binding and the N terminal domain compared to BA.1, we analyzed whether BA.2 shows further immune escape relative to BA.1.MethodsWe characterized neutralization profiles against the new BA.2 omicron variant in plasma samples from a variety of individuals with different numbers of exposures to infection/vaccination, including samples from previously virus-naïve, BA.2 omicron-infected individuals. To illustrate antigenic differences of the two omicron sub-variants and pre-omicron variants we performed antigenic cartography and generated antibody landscapes.ResultsUnvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map, which included all Variants of Concern and both BA.1 and BA.2 omicron sub-variants, showed that both omicron sub-variants are distinct to pre-omicron variants, but that the two omicron variant are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the whole antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distinct variants.ConclusionsHere, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations.

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“…Our findings indicate that booster vaccination with mRNA and adenoviral-vectored vaccines could increase the neutralizing antibody titers and coverage against omicron BA.1 and BA.2. Consistent results showed an improvement in neutralization sensitivity against BA.1 and BA.2 after individuals were boosted with the mRNA vaccine [30,33]. Although both subvariants shared several common amino acid changes, the unique mutations found in each subvariant might affect the differences in neutralization potency [32].…”

Section: Discussionmentioning

confidence: 91%

Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination

Suntronwong

Kanokudom

Auphimai

et al. 2022

Preprint

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BackgroundThe coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion because it harbors mutations even in individuals with complete vaccination. Here, we examine the capability of the booster vaccination to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T-cell responses.MethodsA total of 167 participants primed with heterologous CoronaVac/AZD1222 were enrolled to receive AZD1222, BNT162b2, or mRNA-1273 as a booster dose. Reactogenicity was recorded. Binding antibody, neutralizing antibody (NAb) titers against omicron BA.1 and BA.2, and total interferon gamma (IFN-γ) post-booster responses were measured.ResultsA substantial loss in neutralizing potency to omicron variant was found at 4 to 5 months after receiving the heterologous CoronaVac/AZD1222. Following booster vaccination, a significant increase in binding antibodies and neutralizing activities toward delta and omicron variants was observed. Neutralization to omicron BA.1 and BA.2 were comparable, showing the highest titers after boosted mRNA-1273 followed by BNT162b2 and AZD1222. Notably, boosted individuals with mRNA vaccines could induce T cell response. Reactogenicity was mild to moderate without serious adverse events.ConclusionsOur findings highlight that the booster vaccination could overcome immunity wanes and provide adequate NAbs coverage against omicron BA.1 and BA.2.

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Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines

Cited by 35 publications

References 75 publications

Structural and functional characteristics of SARS-CoV-2 Omicron subvariant BA.2 spike

Structural and functional characteristics of SARS-CoV-2 Omicron subvariant BA.2 spike

BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants

Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination

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