Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages

Xia, Hongjie; Yeung, Jason; Kalveram, Birte; Bills, Cody J.; Chen, John Yun-Chung; Kurhade, Chaitanya; Zou, Jing; Widen, Steven G.; Mann, Brian R.; Kondor, Rebecca; Davis, C. Todd; Zhou, Bin; Wentworth, David E.; Xie, Xuping; Shi, Pei–Yong

doi:10.1080/22221751.2022.2161422

Cited by 15 publications

(12 citation statements)

References 42 publications

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“…Another limitation of our research may be the fact that the Enzyme-Linked Immunosorbent Assay (ELISA) assay was coated with a particular Omicron subvariant (BA.1) limiting the generalizability of our finding to other Omicron subvariants. However, antigenic mapping studies revealed Omicron subvariants to be antigenically distinct to previous VOCs (44)(45)(46), and individuals responding to the BA.1 subvariant have been shown to exhibit more comparable humoral immune response among other Omicron subvariants as opposed to more antigenically distinct pre-Omicron variants and vice versa (44,47). This relation between Omicron subvariants is also reflected in clinical data, showing a similar disease severity among Omicron subvariants (26).…”

Section: Strengths and Limitationsmentioning

confidence: 84%

Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination

Harthaller,

Falkensammer,

Bante

et al. 2023

Front. Immunol.

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IntroductionThe rapid evolution of SARS-CoV-2 has posed a challenge to long-lasting immunity against the novel virus. Apart from neutralizing function, binding antibodies induced by vaccination or infection play an important role in containing the infection. MethodsTo determine the proportion of wild-type (WT)–generated antibodies recognizant of more recent variants, plasma samples from either SARS-CoV-2 WT-infected (n = 336) or double-mRNA (Comirnaty)–vaccinated individuals (n = 354, age and sex matched to the convalescent group) were analyzed for binding antibody capacity against the S1 protein of the BA.1 omicron variant. ResultsOverall, 38.59% (95% CI, 37.01– 40.20) of WT-generated antibodies recognized Omicron BA.1 S1 protein [28.83% (95% CI, 26.73–30.91) after infection and 43.46% (95% CI, 41.61–45.31) after vaccination; p < 0.001]. Although the proportion of WT-generated binding and neutralizing antibodies also binding to BA.1 is substantially reduced, the avidity of the remaining antibodies against the Omicron variant was non-inferior to that of the ancestral virus: Omicron: 39.7% (95% CI: 38.1–41.3) as compared to the avidity to WT: 27.0% (95% CI, 25.5–28.4), respectively (p < 0.001). Furthermore, we noticed a modestly yet statistically significant higher avidity toward the Omicron epitopes among the vaccinated group (42.2%; 95% CI, 40.51–43.94) as compared to the convalescent counterparts (36.4%; 95% CI, 33.42–38.76) (p = 0.003), even after adjusting for antibody concentration. DiscussionOur results suggest that an aspect of functional immunity against the novel strain was considerably retained after WT contact, speculatively counteracting the impact of immune evasion toward neutralization of the strain. Higher antibody levels and cross-binding capacity among vaccinated individuals suggest an advantage of repeated exposure in generating robust immunity.

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Section: Strengths and Limitationsmentioning

confidence: 84%

Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination

Harthaller,

Falkensammer,

Bante

et al. 2023

Front. Immunol.

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“…Infectious virus from experiments was quantified using plaque assays performed as previously described using Vero E6-TMPRSS2 cells [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

“…HAE cells were infected with a mix of the WA1 or mutant virus with an equal MOI of 0.4 and samples were collected as previously described [ 30 ]. For analysis, RNA was purified from each sample and cDNA fragments corresponding to codon positions 72–147 of nsp6 were generated using the SuperScript™ IV One-Step RT–PCR System.…”

Section: Methodsmentioning

confidence: 99%

Mutations in SARS-CoV-2 variant nsp6 enhance type-I interferon antagonism

Bills

Xia

Chen

et al. 2023

Emerging Microbes & Infections

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve after its emergence. Given its importance in viral infection and vaccine development, mutations in the viral Spike gene have been studied extensively; however, the impact of mutations outside the Spike gene are poorly understood. Here, we report that a triple deletion (ΔSGF or ΔLSG) in nonstructural protein 6 (nsp6) independently acquired in Alpha and Omicron sublineages of SARS-CoV-2 augments nsp6-mediated antagonism of type-I interferon (IFN-I) signaling. Specifically, these triple deletions enhance the ability of mutant nsp6 to suppress phosphorylation of STAT1 and STAT2. A parental SARS-CoV-2 USA-WA1/2020 strain containing the nsp6 ΔSGF deletion (ΔSGF-WA1) shows reduced susceptibility to IFN-I treatment in vitro , outcompetes the parental strain in human primary airway cultures, and increases virulence in mice; however, the ΔSGF-WA1 virus is less virulent than the Alpha variant (which has the nsp6 ΔSGF deletion and additional mutations in other genes). Analyses of host responses from ΔSGF-WA1-infected mice and primary airway cultures reveal activation of pathways indicative of a cytokine storm. These results provide evidence that mutations outside the Spike protein affect virus-host interactions and may alter pathogenesis of SARS-CoV-2 variants in humans.

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“…All cells were maintained at 37°C with 5% CO2. The infectious clones derived USA-WA1/2020 SARS-CoV-2, ∆3678, and the BA.5 variant were generated as previously described [7,17,18].…”

Section: Methodsmentioning

confidence: 99%

A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity

Adam

Kalveram

Chen

et al. 2023

Preprint

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An attenuated SARS-CoV-2 virus with modified viral transcriptional regulatory sequences and deletion of open-reading frames 3, 6, 7 and 8 (∆3678) was previously reported to protect hamsters from SARS-CoV-2 infection and transmission. Here we report that a single-dose intranasal vaccination of ∆3678 protects K18-hACE2 mice from wild-type or variant SARS-CoV-2 challenge. Compared with wild-type virus infection, the ∆3678 vaccination induces equivalent or higher levels of lung and systemic T cell, B cell, IgA, and IgG responses. The results suggest ∆3678 as an attractive mucosal vaccine candidate to boost pulmonary immunity against SARS-CoV-2.

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Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages

Cited by 15 publications

References 42 publications

Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination

Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination

Mutations in SARS-CoV-2 variant nsp6 enhance type-I interferon antagonism

A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity

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