Limited neutralisation of the SARS-CoV-2 Omicron subvariants BA.1 and BA.2 by convalescent and vaccine serum and monoclonal antibodies

Wilhelm, Alexander; Widera, Marek; Grikscheit, Katharina; Toptan, Tuna; Schenk, Barbara; Pallas, Christiane; Metzler, Melinda; Kohmer, Niko; Hoehl, Sebastian; Marschalek, Rolf; Herrmann, Eva; Helfritz, Fabian; Wolf, Timo; Goetsch, Udo; Ciesek, Sandra

doi:10.1016/j.ebiom.2022.104158

Cited by 139 publications

(76 citation statements)

References 64 publications

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“…Antibody-mediated neutralization of authentic SARS-CoV-2 variants was performed as described before [40] using heat inactivated and serially diluted plasma samples (1:2). Samples were incubated with 4000 TCID50/mL of each SARS-CoV-2 variants.…”

Section: Methodsmentioning

confidence: 99%

Cellular and humoral immunity towards parental SARS-CoV-2 and variants of concern after two doses of the NVX-CoV2373-vaccine in comparison to homologous BNT162b and mRNA1273 regimens

Hielscher

Schmidt

Klemis

et al. 2022

Preprint

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The NVX-CoV2373-vaccine has recently been licensed, although data on vaccine-induced humoral and cellular immunity towards the parental strain and variants of concern (VOCs) in comparison to dual-dose mRNA-regimens are limited. In this observational study including 66 participants, we show that NVX-CoV2373-induced IgG-levels were lower than after vaccination with BNT162b2 or mRNA-1273 (n=22 each, p=0.006). Regardless of the vaccine and despite different IgG-levels, neutralizing activity towards VOCs was highest for Delta, followed by BA.2 and BA.1. Interestingly, spike-specific CD8 T-cell levels after NVX-CoV2373-vaccination were significantly lower and were detectable in 3/22 (14%) individuals only. In contrast, spike-specific CD4 T-cells were induced in 18/22 (82%) individuals. However, CD4 T-cell levels were lower (p<0.001), had lower CTLA-4 expression (p<0.0001) and comprised less multifunctional cells co-expressing IFNγ, TNFα and IL-2 (p=0.0007) as compared to mRNA-vaccinated individuals. Unlike neutralizing antibodies, NVX-CoV2373-induced CD4 T cells cross-reacted to all tested VOCs from Alpha to Omicron, which may hold promise to protect from severe disease.

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Section: Methodsmentioning

confidence: 99%

Cellular and humoral immunity towards parental SARS-CoV-2 and variants of concern after two doses of the NVX-CoV2373-vaccine in comparison to homologous BNT162b and mRNA1273 regimens

Hielscher

Schmidt

Klemis

et al. 2022

Preprint

Self Cite

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“…In the future, administration of long-lasting monoclonal antibody preparations might also enable passive immunization to be provided in patients with refractory immunization failure. Of note, although several antibody preparations with a high neutralization capacity against Alpha, Beta and Gamma SARS-CoV-2 VOC were not protective against Omicron, the monoclonal antibody sotrovimab provided in vitro neutralization against Delta and some subvariants of Omicron 171 – 173 .…”

Section: Strategies To Improve Vaccination Responsesmentioning

confidence: 99%

Vaccination in patients with kidney failure: lessons from COVID-19

2022

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Infection is the second leading cause of death in patients with chronic kidney disease (CKD). Adequate humoral (antibody) and cellular (T cell-driven) immunity are required to minimize pathogen entry and promote pathogen clearance to enable infection control. Vaccination can generate cellular and humoral immunity against specific pathogens and is used to prevent many life-threatening infectious diseases. However, vaccination efficacy is diminished in patients with CKD. Premature ageing of the immune system and chronic systemic low-grade inflammation are the main causes of immune alteration in these patients. In the case of SARS-CoV-2 infection, COVID-19 can have considerable detrimental effects in patients with CKD, especially in those with kidney failure. COVID-19 prevention through successful vaccination is therefore paramount in this vulnerable population. Although patients receiving dialysis have seroconversion rates comparable to those of patients with normal kidney function, most kidney transplant recipients could not generate humoral immunity after two doses of the COVID-19 vaccine. Importantly, some patients who were not able to produce antibodies still had a detectable vaccine-specific T cell response, which might be sufficient to prevent severe COVID-19. Correlates of protection against SARS-CoV-2 have not been established for patients with kidney failure, but they are urgently needed to enable personalized vaccination regimens.

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“…Nasopharyngeal swabs derived authentic SARS-CoV-2 isolates and original sample material were used for specificity testing as described previously [9]. All cell culture work involving infectious SARS-CoV-2 was performed under biosafety level 3 (BSL-3) conditions.…”

Section: Specificity Testing Using Authentic Sars-cov-2 Isolatesmentioning

confidence: 99%

Early Detection of SARS-CoV-2 Omicron BA.4/5 in German wastewater

Wilhelm

Schoth

Meinert-Berning

et al. 2022

Preprint

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Wastewater-based SARS-CoV-2 epidemiology (WBE) has been established as an important tool to support individual testing strategies. Omicron sub-variants BA.4/5 have spread globally displacing the predeceasing variants. Due to the severe transmissibility and immune escape potential of BA.4/5, early monitoring was required to asses and implement countermeasures in time. In this study, we monitored the prevalence of SARS-CoV-2 BA.4/5 at six municipal wastewater treatment plants (WWTPs) in the Federal State of North-Rhine-Westphalia (NRW, Germany) in May and June 2022. Initially, L452R-specific primers/probes originally designed for SARS-CoV-2 Delta detection were validated using inactivated authentic viruses and evaluated for their suitability to detect BA.4/5. Subsequently, the assay was used for RT-qPCR analysis of RNA purified from wastewater obtained twice a week at six WWTPs. The occurrence of L452R carrying RNA was detected in early May 2022 and the presence of BA.4/5 was confirmed by variant-specific single nucleotide polymorphism PCR (SNP-PCR) targeting E484A/F486V. Finally, the mutant fractions were quantitatively monitored by digital PCR confirming BA.4/5 as the majority variant by 5th June 2022. In conclusions, the successive workflow using RT-qPCR, variant-specific SNP-PCR, and RT-dPCR demonstrates the strength of WBE as a versatile tool to rapidly monitor variant spreading independent of individual test capacities.

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Limited neutralisation of the SARS-CoV-2 Omicron subvariants BA.1 and BA.2 by convalescent and vaccine serum and monoclonal antibodies

Cited by 139 publications

References 64 publications

Cellular and humoral immunity towards parental SARS-CoV-2 and variants of concern after two doses of the NVX-CoV2373-vaccine in comparison to homologous BNT162b and mRNA1273 regimens

Cellular and humoral immunity towards parental SARS-CoV-2 and variants of concern after two doses of the NVX-CoV2373-vaccine in comparison to homologous BNT162b and mRNA1273 regimens

Vaccination in patients with kidney failure: lessons from COVID-19

Early Detection of SARS-CoV-2 Omicron BA.4/5 in German wastewater

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