Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity Against SARS-CoV-2 After Natural Infection Is More Potent Than After Vaccination

Rieke, Gereon J; Bremen, Kathrin van; Bischoff, Jenny; Vinh, Michael To; Monin, Malte B; Schlabe, Stefan; Raabe, Jan; Kaiser, Kim M; Finnemann, Claudia; Odainic, Alexandru; Kudaliyanage, Anushka; Latz, Eicke; Strassburg, Christian P.; Boesecke, Christoph; Schmidt, Susanne V.; Krämer, Benjamin; Rockstroh, Jürgen K.; Nattermann, Jacob

doi:10.1093/infdis/jiac060

Cited by 20 publications

(21 citation statements)

References 13 publications

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“…However, the antibodies triggering ADCC were not the ones targeting the spike protein, the viral component used in many current vaccines. In fact, further experiments revealed that vaccination-induced antibodies targeting the spike protein poorly engaged natural killer cells, a result in line with a study showing that vaccination-induced antibodies are not as good at mediating ADCC compared to infection-induced antibodies ( Rieke et al, 2022 ). Fielding et al then went on to reveal that the antibodies involved in ADCC were those produced in reaction to other viral proteins expressed at the surface of infected cells.…”

supporting

confidence: 78%

Taking on SARS-CoV-2

Brlić

Brizić

2022

eLife

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supporting

confidence: 78%

Taking on SARS-CoV-2

Brlić

Brizić

2022

eLife

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“…COVID-19 vaccines in NHP ( 29 ) and humans ( 1 ) have reported important roles for both neutralizing and non-neutralizing antibodies in reducing viral infection and COVID-19 disease. Further investigation into the role of non-neutralizing antibody functions in protection, including ADCC are needed ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

A replicon RNA vaccine induces durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned

O’Connor

Hawman

Meade-White

et al. 2022

Preprint

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The global SARS-CoV-2 pandemic prompted rapid development of COVID-19 vaccines. Although several vaccines have received emergency approval through various public health agencies, the SARS-CoV-2 pandemic continues. Emergent variants of concern, waning immunity in the vaccinated, evidence that vaccines may not prevent transmission and inequity in vaccine distribution have driven continued development of vaccines against SARS-CoV-2 to address these public health needs. In this report, we evaluated a novel self-amplifying replicon RNA vaccine against SARS-CoV-2 in a pigtail macaque model of COVID-19 disease. We found that this vaccine elicited strong binding and neutralizing antibody responses. While binding antibody responses were sustained, neutralizing antibody waned to undetectable levels after six months but were rapidly recalled and conferred protection from disease when the animals were challenged 7 months after vaccination as evident by reduced viral replication and pathology in the lower respiratory tract, reduced viral shedding in the nasal cavity and lower concentrations of pro-inflammatory cytokines in the lung. Cumulatively, our data demonstrate in pigtail macaques that a self-amplifying replicon RNA vaccine can elicit durable and protective immunity to SARS-CoV-2 infection. Furthermore, these data provide evidence that this vaccine can provide durable protective efficacy and reduce viral shedding even after neutralizing antibody responses have waned to undetectable levels.

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“…Amongst these, NK cell mediated ADCC is the most potent and consistent. While VOC might escape neutralization by mutational changes in the receptor binding domains, NK cell mediated ADCC effector functions is more resilient and remain preserved across the variants [14][15][16][17] for longer periods 18 .…”

Section: Discussionmentioning

confidence: 99%

Augmenting vaccine efficacy against delta variant with ‘Mycobacterium-w’ mediated modulation of NK-ADCC and TLR-MYD88 pathways

Jaiswal

Saifullah²,

Arunachalam³

et al. 2022

Preprint

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Mycobacterium-w (Mw), was shown to boost adaptive natural killer (ANK) cells and protect against COVID-19 during the first wave of the pandemic. As a follow-up of the trial, 50 healthcare workers (HCW) who had received Mw in September 2020 and subsequently received at least one dose of ChAdOx1 nCoV-19 vaccine (Mw+ChAdOx1 group) were monitored for symptomatic COVID-19, during a major outbreak with the delta variant of SARS-CoV-2 (April-June, 2021), along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Despite 48% having received just a single dose of the vaccine in Mw+ChAdOx1 group, only 2 had mild COVID-19, compared to 36 infections in the ChAdOx1 group (HR-0.46, p=0.009). Transcriptomic studies revealed an enhanced adaptive NK cell-dependent ADCC in the Mw+ChAdOx1 group, along with downregulation of TLR2-MYD88 pathway and concomitant attenuation of downstream inflammatory pathways. This might have resulted in robust protection during the pandemic with the delta variant.

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Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity Against SARS-CoV-2 After Natural Infection Is More Potent Than After Vaccination

Cited by 20 publications

References 13 publications

Taking on SARS-CoV-2

Taking on SARS-CoV-2

A replicon RNA vaccine induces durable protective immunity from SARS-CoV-2 in nonhuman primates after neutralizing antibodies have waned

Augmenting vaccine efficacy against delta variant with ‘Mycobacterium-w’ mediated modulation of NK-ADCC and TLR-MYD88 pathways

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