SARS-CoV-2 Related Antibody-Dependent Enhancement Phenomena In Vitro and In Vivo

Nakayama, Emi E.; Shioda, Tatsuo

doi:10.3390/microorganisms11041015

Cited by 15 publications

(8 citation statements)

References 160 publications

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“…It is not clear whether the finding that secondary infection resulted in more severe outcomes than the primary infection in a veteran cohort [72] can be generalized to a younger population. If the anti-S antibody cannot neutralize the secondary infection due to the decay of antibodies and/or escape the mutation of newly emerged variants such as BA.2.86 [73], the acquired anti-N antibody could be one of the causes of IL-6 induction [74]. Higher cytokine levels can promote a state of hyperinflammation that is harmful to host cells [75].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of IL-6 Production Induced by SARS-CoV-2 Nucleocapsid Protein and Bangladeshi COVID-19 Patients’ Sera

Hasan,

Rahim,

Nakayama

et al. 2023

Viruses

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Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 that can have detrimental effects on multiple organs and accelerate patient mortality. This study, which encompassed 130 confirmed COVID-19 patients who were assessed at three different time points (i.e., 3, 7, and 12 days) after the onset of symptoms, investigated interleukin-6 (IL-6) enhancement induced by a viral nucleocapsid (N) protein from a myeloid cell line. Disease severity was categorized as mild, moderate, or severe. The severe cases were characterized as having significant elevations in serum IL-6, C-reactive protein, D-dimer, ferritin, creatinine, leukocytes, and neutrophil-to-lymphocyte ratio and decreased hemoglobin, hematocrit, and albumin levels compared with mild and moderate cases. To evaluate IL-6-inducing activity, heat-inactivated sera from these patients were incubated with and without the N protein. The findings showed a progressive increase in IL-6 production in severe cases upon N protein stimulation. There was a strong correlation between anti-N antibodies and levels of IL-6 secreted by myeloid cells in the presence of N protein and sera, indicating the crucial role that the anti-N antibody plays in inducing IL-6 production. Uncontrolled IL-6 production played a pivotal role in disease pathogenesis, exacerbating both disease severity and mortality. Efficiently targeting the N protein could potentially be employed as a therapeutic strategy for regulating the immune response and alleviating inflammation in severe cases.

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Section: Discussionmentioning

confidence: 99%

Enhancement of IL-6 Production Induced by SARS-CoV-2 Nucleocapsid Protein and Bangladeshi COVID-19 Patients’ Sera

Hasan,

Rahim,

Nakayama

et al. 2023

Viruses

Self Cite

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“…This was reported in both convalescent sera and sera collected from acute patients. Several papers indicated that pre‐existing immunity could shape the immune response to SARS‐CoV‐2 harmfully or beneficially 41 . Hence, the order of exposure to different CoV may lead to ADE response in some individuals.…”

Section: Discussionmentioning

confidence: 99%

Antibody‐dependent enhancement (ADE) of SARS‐CoV‐2 in patients exposed to MERS‐CoV and SARS‐CoV‐2 antigens

Thomas,

Smatti,

Alsulaiti

et al. 2024

Journal of Medical Virology

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This study evaluated the potential for antibody‐dependent enhancement (ADE) in serum samples from patients exposed to Middle East respiratory syndrome coronavirus (MERS‐CoV). Furthermore, we evaluated the effect of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination on ADE in individuals with a MERS infection history. We performed ADE assay in sera from MERS recovered and SARS‐CoV‐2‐vaccinated individuals using BHK cells expressing FcgRIIa, SARS‐CoV‐2, and MERS‐CoV pseudoviruses (PVs). Further, we analyzed the association of ADE to serum IgG levels and neutralization. Out of 16 MERS patients, nine demonstrated ADE against SARS‐CoV‐2 PV, however, none of the samples demonstrated ADE against MERS‐CoV PV. Furthermore, out of the seven patients exposed to SARS‐CoV‐2 vaccination after MERS‐CoV infection, only one patient (acutely infected with MERS‐CoV) showed ADE for SARS‐CoV‐2 PV. Further analysis indicated that IgG1, IgG2, and IgG3 against SARS‐CoV‐2 S1 and RBD subunits, IgG1 and IgG2 against the MERS‐CoV S1 subunit, and serum neutralizing activity were low in ADE‐positive samples. In summary, samples from MERS‐CoV‐infected patients exhibited ADE against SARS‐CoV‐2 and was significantly associated with low levels of neutralizing antibodies. Subsequent exposure to SARS‐CoV‐2 vaccination resulted in diminished ADE activity while the PV neutralization assay demonstrated a broadly reactive antibody response in some patient samples.

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“…The loss of infectivity of target virus in neutralization assays due to nonspecific binding of antibodies or due to high concentrations of (heterologous) serum components interfering with the infection process at the surface of susceptible cells may lead to false-positive VNT titers for sera [ 38 , 39 ]. In addition, the antibody-dependent enhancement (ADE) of virus infection in VNT assays due to the binding of sub- and non-neutralizing antibodies to virus particles may enhance viral infections [ 40 ]. We, therefore, developed neutralization assays for BCV, SARS-CoV-2 and TGEV using high ascending virus concentrations, a fixed serum dilution of 1:50 instead of serial dilutions and incubated virus–serum mixtures in a serum-free culture medium.…”

Section: Discussionmentioning

confidence: 99%

Cross-Reactivity of Human, Wild Boar, and Farm Animal Sera from Pre- and Post-Pandemic Periods with Alpha- and Βeta-Coronaviruses (CoV), including SARS-CoV-2

Hulst,

Kant,

Harders-Westerveen

et al. 2023

Viruses

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Panels of pre- and post-pandemic farm animals, wild boar and human sera, including human sera able to neutralize SARS-CoV-2 in vitro, were tested in serological tests to determine their cross-reactivity with β- and α-CoV originating from farm animals. Sera were tested in neutralization assays with high ascending concentrations (up to 1 × 104 TCID50 units/well) of β-CoV Bovine coronavirus (BCV), SARS-CoV-2, and porcine α-CoV-transmissible gastroenteritis virus (TGEV). In addition, sera were tested for immunostaining of cells infected with β-CoV porcine hemagglutinating encephalomyelitis (PHEV). Testing revealed a significantly higher percentage of BCV neutralization (78%) for sera of humans that had experienced a SARS-CoV-2 infection (SARS-CoV-2 convalescent sera) than was observed for human pre-pandemic sera (37%). Also, 46% of these human SARS-CoV-2 convalescent sera neutralized the highest concentration of BCV (5 × 103 TCID50/well) tested, whereas only 9.6% of the pre-pandemic sera did. Largely similar percentages were observed for staining of PHEV-infected cells by these panels of human sera. Furthermore, post-pandemic sera collected from wild boars living near a densely populated area in The Netherlands also showed a higher percentage (43%) and stronger BCV neutralization than was observed for pre-pandemic sera from this area (21%) and for pre- (28%) and post-pandemic (20%) sera collected from wild boars living in a nature reserve park with limited access for the public. High percentages of BCV neutralization were observed for pre- and post-pandemic sera of cows (100%), pigs (up to 45%), sheep (36%) and rabbits (60%). However, this cross-neutralization was restricted to sera collected from specific herds or farms. TGEV was neutralized only by sera of pigs (68%) and a few wild boar sera (4.6%). None of the BCV and PHEV cross-reacting human pre-pandemic, wild boar and farm animal sera effectively neutralized SARS-CoV-2 in vitro. Preexisting antibodies in human sera effectively neutralized the animal β-CoV BCV in vitro. This cross-neutralization was boosted after humans had experienced a SARS-CoV-2 infection, indicating that SARS-CoV-2 activated a “memory” antibody response against structurally related epitopes expressed on the surface of a broad range of heterologous CoV, including β-CoV isolated from farm animals. Further research is needed to elucidate if a symptomless infection or environmental exposure to SARS-CoV-2 or another β-CoV also triggers such a “memory” antibody response in wild boars and other free-living animals.

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SARS-CoV-2 Related Antibody-Dependent Enhancement Phenomena In Vitro and In Vivo

Cited by 15 publications

References 160 publications

Enhancement of IL-6 Production Induced by SARS-CoV-2 Nucleocapsid Protein and Bangladeshi COVID-19 Patients’ Sera

Enhancement of IL-6 Production Induced by SARS-CoV-2 Nucleocapsid Protein and Bangladeshi COVID-19 Patients’ Sera

Antibody‐dependent enhancement (ADE) of SARS‐CoV‐2 in patients exposed to MERS‐CoV and SARS‐CoV‐2 antigens

Cross-Reactivity of Human, Wild Boar, and Farm Animal Sera from Pre- and Post-Pandemic Periods with Alpha- and Βeta-Coronaviruses (CoV), including SARS-CoV-2

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