Antibody-Dependent Enhancement of SARS-CoV-2 Infection Is Mediated by the IgG Receptors FcγRIIA and FcγRIIIA but Does Not Contribute to Aberrant Cytokine Production by Macrophages

Maemura, Tadashi; Kuroda, Makoto; Armbrust, Tammy; Yamayoshi, Seiya; Halfmann, Peter; Kawaoka, Yoshihiro

doi:10.1128/mbio.01987-21

Cited by 74 publications

(79 citation statements)

References 29 publications

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“…Although an ADE of infection was observed in macrophages derived from monocytes infected with SARS-CoV-2, including its variants, the expression of proinflammatory cytokines/chemokines was not increased in macrophages. Thus, these antibodies do not contribute to excessive cytokine production by macrophages [58]. The preceding description reinforces the idea of ruling out a possible ADE in COVID-19, since unlike infections by some of the DENV viruses, SARS-CoV-2 predominantly infects the respiratory epithelium, not macrophages [57].…”

Section: Discussionsupporting

confidence: 68%

The Usefulness of Peripheral Blood Cell Counts to Distinguish COVID-19 from Dengue during Acute Infection

et al. 2022

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COVID-19 and dengue disease are challenging to tell apart because they have similarities in clinical and laboratory features during the acute phase of infection, leading to misdiagnosis and delayed treatment. The present study evaluated peripheral blood cell count accuracy to distinguish COVID-19 non-critical patients from non-severe dengue cases between the second and eleventh day after symptom onset. A total of 288 patients infected with SARS-CoV-2 (n = 105) or dengue virus (n = 183) were included in this study. Neutrophil, platelet, and lymphocyte counts were used to calculate the neutrophil–lymphocyte ratio (NLR), the platelet–lymphocyte ratio (PLR), and the neutrophil–lymphocyte*platelet ratio (NLPR). The logistic regression and ROC curves analysis revealed that neutrophil and platelet counts, NLR, LPR, and NLPR were higher in COVID-19 than dengue. The multivariate predictive model showed that the neutrophils, platelets, and NLPR were independently associated with COVID-19 with a good fit predictive value (p = 0.1041). The neutrophil (AUC = 0.95, 95% CI = 0.84–0.91), platelet (AUC = 0.89, 95% CI = 0.85–0.93) counts, and NLR (AUC = 0.88, 95% CI = 0.84–0.91) were able to discriminate COVID-19 from dengue with high sensitivity and specificity values (above 80%). Finally, based on predicted probabilities on combining neutrophils and platelets with NLR or NLPR, the adjusted AUC was 0.97 (95% CI = 0.94–0.98) to differentiate COVID-19 from dengue during the acute phase of infection with outstanding accuracy. These findings might suggest that the neutrophil, platelet counts, and NLR or NLPR provide a quick and cost-effective way to distinguish between dengue and COVID-19 in the context of co-epidemics in low-income tropical regions.

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Section: Discussionsupporting

confidence: 68%

The Usefulness of Peripheral Blood Cell Counts to Distinguish COVID-19 from Dengue during Acute Infection

et al. 2022

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“…62,63 It is unclear how widely Th2-type vaccine responses induced by coronavirus vaccines could lead to clinically meaningful immune complications, with no evidence of vaccine-associated enhanced respiratory disease (VAERD) or antibody-dependent enhancement (ADE) of virus infection and disease reported in any human trials for SARS-CoV-1, SARS-CoV-2, or Middle East Respiratory Syndrome (MERS) vaccines. 64,65 Regardless, the AAHI-SC2 vaccine clearly induces strong Th1-biased immunity suggesting a favorable immunogenicity profile for a SARS-CoV-2 vaccine.…”

Section: Lyophilized Aahi-sc2 Vaccine Is Thermostable Enabling Long-t...mentioning

confidence: 99%

A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability

Voigt¹,

Gerhardt

Hanson³

et al. 2022

Preprint

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mRNA vaccines were the first to be authorized for use against SARS-CoV-2 and have since demonstrated high efficacy against serious illness and death. However, limitations in these vaccines have been recognized due to their requirement for cold storage, short durability of protection, and lack of access in low-resource regions. We have developed an easily-manufactured, potent self-amplifying RNA (saRNA) vaccine against SARS-CoV-2 that is stable at room temperature. This saRNA vaccine is formulated with a nanostructured lipid carrier (NLC), providing enhanced stability, improved manufacturability, and protection against degradation. In preclinical studies, this saRNA/NLC vaccine induced strong humoral immunity, as demonstrated by high pseudovirus neutralization titers to the Alpha, Beta, and Delta variants of concern and induction of long-lived bone marrow-resident antibody secreting cells. Robust Th1-biased T-cell responses were also observed after prime or homologous prime-boost in mice. Notably, the saRNA/NLC platform demonstrated thermostability at room temperature for at least 6 months when lyophilized. Taken together, this saRNA delivered by NLC represents a potential improvement in RNA technology that could allow wider access to RNA vaccines for the current COVID-19 and future pandemics.

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“…In cases of SARS-CoV viruses, the antibodies that neutralized most variants were found to be able to enhance immune cell entry of the mutant virus, which, in turn, worsened the disease the vaccine was designed to protect against ( Tetro, 2020 ; Lee et al, 2020 ). Although ADE is not thought to contribute to excess cytokine production in the context of SARS-CoV-2, IgG ligation of Fc receptors has been shown to contribute to modest ADE of infection ( Maemura et al, 2021 ). Therefore, ADE can hamper vaccine development, as a vaccine may cause the production of suboptimal antibodies.…”

Section: Introductionmentioning

confidence: 99%

ACE2-Fc fusion protein overcomes viral escape by potently neutralizing SARS-CoV-2 variants of concern

Tsai¹,

Khalili²,

Gilchrist³

et al. 2022

Antiviral Research

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Antibody-Dependent Enhancement of SARS-CoV-2 Infection Is Mediated by the IgG Receptors FcγRIIA and FcγRIIIA but Does Not Contribute to Aberrant Cytokine Production by Macrophages

Abstract: Viruses infect cells mainly via specific receptors at the cell surface. Antibody-dependent enhancement (ADE) of infection is an alternative mechanism of infection for viruses to infect immune cells that is mediated by antibodies and IgG receptors (FcγRs).

Cited by 74 publications

References 29 publications

The Usefulness of Peripheral Blood Cell Counts to Distinguish COVID-19 from Dengue during Acute Infection

The Usefulness of Peripheral Blood Cell Counts to Distinguish COVID-19 from Dengue during Acute Infection

A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability

ACE2-Fc fusion protein overcomes viral escape by potently neutralizing SARS-CoV-2 variants of concern

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