SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents

García-Valtanen, Pablo; Hope, Christopher; Masavuli, Makutiro G.; Yeow, Arthur Eng Lip; Balachandran, Harikrishnan; Mekonnen, Zelalem; Al-Delfi, Zahraa; Abayasingam, Arunasingam; Agapiou, David; Stella, Alberto Ospina; Aggarwal, Anupriya; Bouras, George; Gummow, Jason; Ferguson, Catherine; O’Connor, Stephanie; McCartney, Erin M.; Lynn, David J.; Maddern, Guy; Gowans, Eric J.; Reddi, Benjamin; Shaw, David R.; Kok-Lim, Chuan; Beard, Michael R.; Weiskopf, Daniela; Sette, Alessandro; Turville, Stuart; Bull, Rowena A.; Barry, Simon C.; Grubor‐Bauk, Branka

doi:10.1016/j.xcrm.2022.100651

Cited by 30 publications

(32 citation statements)

References 80 publications

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“…Mutated RBD proteins in our study, representing the Beta, Gamma and Delta VoC, all demonstrated reduced antibody recognition. 20,21,[23][24][25] Hence, we can use the antibody and Bmem cell responses to these VoC as a model of variants that partially escape the current Wuhan based BNT162b2 vaccination. We show that the second vaccine dose increased the capacity of antibodies and Bmem to bind VoC.…”

Section: Discussionmentioning

confidence: 99%

“…22 Still, antibody recognition of Beta and Gamma are more greatly impacted than Delta. 20,[23][24][25][26][27] In previously-infected individuals, one vaccine dose elicits neutralizing levels of antibody to VoC to the same degree as two doses in naive individuals. 14 This suggests that reactivation of pre-existing Bmem to undergo a secondary GC response improves recognition of VoCs.…”

Section: Introductionmentioning

confidence: 99%

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Double-dose mRNA vaccination to SARS-CoV-2 progressively increases recognition of variants-of-concern by Spike RBD-specific memory B cells

Hartley

Edwards

Varese

et al. 2022

Preprint

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Background: SARS-CoV-2 vaccination with BNT162b2 (Pfizer BioNTech) has been shown to be 95% effective. Double-dose vaccination generates high levels of spike-specific antibodies, memory B cells (Bmem) and T cells. However, variants of concern (VoC) with mutations in the spike Receptor Binding Domain (RBD) can evade antibody responses. Booster vaccinations improve antibody recognition of VoC, but it is unclear if this is due to higher total antibodies or their capacity to bind VoC. We here addressed the capacity of surface Ig on single Wuhan-specific Bmem after first and second dose BNT162b2 vaccination to recognize variant RBD. Methods: Samples were collected from 30 healthy COVID-19 naive individuals pre-BNT162b2 vaccination, 3 weeks post-dose 1 and 4-weeks post-dose 2. Plasma antibodies and Bmem were evaluated using recombinant RBD proteins of the Wuhan, Gamma and Delta strains. Results: All individuals generated a robust antibody response to BNT162b2 vaccination with all participants producing neutralizing antibodies following dose 2. IgM+ and IgG+ RBD-specific Bmem were generated after one vaccine dose, and those expressing IgG1 increased in absolute number after dose 2. The majority of RBD-specific Bmem bound the Gamma and/or Delta variants, and this proportion significantly increased after the second dose. Conclusion: The second dose of BNT162b2 increases the number of circulating Ig-class switched RBD-specific Bmem. Importantly, the second dose of vaccination is required for a high frequency of RBD-specific Bmem to recognize Gamma and Delta variants. This suggests that dose 2 not only increases the number of RBD-specific Bmem but also the affinity of the Bmem to overcome the point mutations in VoC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Double-dose mRNA vaccination to SARS-CoV-2 progressively increases recognition of variants-of-concern by Spike RBD-specific memory B cells

Hartley

Edwards

Varese

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Several reports have emerged, shedding light on a possible compromise of NAb response, and humoral responses in general, with the emergence of variants ( 52 ). Even though we did not carry out neutralizing assay using other variants, several authors have observed that the antibody response breadth in individuals with different clinical spectra of COVID-19 is reduced against variants of concern, even in severe COVID-19 ( 5 , 53 ). Interestingly, the neutralizing activity against all variants increases after vaccination highlighting their importance as public health policies ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, it is known that viral proteins such as ORF3b and NSP-3 blocked IFN-I pathway and NSP-1, -10, and -16 shutdown host mRNA translation machinery thus contributing to viral pathogenesis ( 4 ). Furthermore, viral evolution has been concentrated in Spike protein, with mutations conferring higher affinity to the cellular receptor, therefore the new variants seem to be more transmissible, ability to evade immunity but its less virulent ( 5 , 6 ). Several host factors have been associated with higher severity as age, gender, presence of comorbidities, and magnitude and characteristics of the innate and adaptive immune responses ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages

et al. 2022

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BackgroundThe COVID-19 pandemic remains a global health problem. As in other viral infections, the humoral immune response against SARS-CoV-2 is thought to be crucial for controlling the infection. However, the dynamic of B cells in the clinical spectrum of this disease is still controversial. This study aimed to characterize B cell subsets and neutralizing responses in COVID-19 patients according to disease severity through a one-month follow-up.MethodsA cohort of 71 individuals with SARS-CoV-2 infection confirmed by RT-PCR were recruited and classified into four groups: i) asymptomatic; ii) symptomatic outpatients; iii) hospitalized in ward, and iv) intensive care unit patients (ICU). Samples were taken at days 0 (inclusion to the study), 7 and 30. B cell subsets and neutralizing antibodies were assessed using multiparametric flow cytometry and plaque reduction neutralization, respectively.ResultsOlder age, male gender and body mass index over 25 were common factors among hospitalized and ICU patients, compared to those with milder clinical presentations. In addition, those requiring hospitalization had more comorbidities. A significant increase in the frequencies of CD19+ cells at day 0 was observed in hospitalized and ICU patients compared to asymptomatic and symptomatic groups. Likewise, the frequency of plasmablasts was significantly increased at the first sample in the ICU group compared to the asymptomatic group, but then waned over time. The frequency of naïve B cells decreased at days 7 and 30 compared to day 0 in hospitalized and ICU patients. The neutralizing antibody titers were higher as the severity of COVID-19 increased; in asymptomatic individuals, it was strongly correlated with the percentage of IgM+ switched memory B cells, and a moderate correlation was found with plasmablasts.ConclusionThe humoral immune response is variable among SARS-CoV-2 infected people depending on the severity and time of clinical evolution. In severe COVID-19 patients, a higher plasmablast frequency and neutralizing antibody response were observed, suggesting that, despite having a robust humoral immunity, this response could be late, having a low impact on disease outcome.

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“…Despite the availability of COVID-19 vaccines, clinical evidence shows that emerging mutations result in unexpected escape from vaccine effect ( 3 ). The protection of existing vaccines may be affected over time against the highly infectious Omicron variant ( 4 ). Currently, few specific antiviral medications have been approved for treating COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Preclinical findings: The pharmacological targets and molecular mechanisms of ferulic acid treatment for COVID-19 and osteosarcoma via targeting autophagy

Pang

Yi²,

Luo³

et al. 2022

Front. Endocrinol.

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The variant virus-based 2019 coronavirus disease (COVID-19) pandemic has reportedly impacted almost all populations globally, characterized by a huge number of infected individuals. Clinical evidence proves that patients with cancer are more easily infected with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) because of immunologic deficiency. Thus, there is an urgent need to develop candidate medications to treat patients with cancer plus COVID-19, including those with osteosarcoma (OS). Ferulic acid, a latent theriacal compound that has anti-tumor and antivirus activities, is discovered to have potential pharmacological use. Thus, in this study, we aimed to screen and determine the potential therapeutic targets of ferulic acid in treating patients with OS plus COVID-19 as well as the pharmacological mechanisms. We applied a well-established integrated methodology, including network pharmacology and molecular docking technique, to detail target prediction, network construction, gene ontology, and pathway enrichment in core targets. The network pharmacology results show that all candidate genes, by targeting autophagy, were the core targets of ferulic acid in treating OS and COVID-19. Through molecular docking analysis, the signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 1 (MAPK1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) were identified as the pharmacological targets of ferulic acid in treating OS. These preclinical findings from bioinformatics analysis altogether effectively determined the pharmacological molecules and mechanisms via targeting autophagy, demonstrating the therapeutic effectiveness of ferulic acid against COVID-19 and OS.

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SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents

Cited by 30 publications

References 80 publications

Double-dose mRNA vaccination to SARS-CoV-2 progressively increases recognition of variants-of-concern by Spike RBD-specific memory B cells

Double-dose mRNA vaccination to SARS-CoV-2 progressively increases recognition of variants-of-concern by Spike RBD-specific memory B cells

Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages

Preclinical findings: The pharmacological targets and molecular mechanisms of ferulic acid treatment for COVID-19 and osteosarcoma via targeting autophagy

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