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J Med Virol . Antibody-dependent enhancement (ADE) of SARS-CoV-2 in patients exposed to MERS-CoV and SARS-CoV-2 antigens

tetano

Editor, Senior Moderator
J Med Virol


. 2024 May;96(5):e29628.
doi: 10.1002/jmv.29628. Antibody-dependent enhancement (ADE) of SARS-CoV-2 in patients exposed to MERS-CoV and SARS-CoV-2 antigens

Swapna Thomas[SUP] 1 2 [/SUP], Maria K Smatti[SUP] 1 [/SUP], Haya Alsulaiti[SUP] 1 3 [/SUP], Hadeel T Zedan[SUP] 1 4 [/SUP], Ali H Eid[SUP] 5 [/SUP], Ali A Hssain[SUP] 6 [/SUP], Laith J Abu Raddad[SUP] 7 [/SUP], Giusy Gentilcore[SUP] 8 [/SUP], Allal Ouhtit[SUP] 2 [/SUP], Asmaa A Althani[SUP] 1 3 [/SUP], Gheyath K Nasrallah[SUP] 1 4 [/SUP], Jean-Charles Grivel[SUP] 8 [/SUP], Hadi M Yassine[SUP] 1 4 [/SUP]



Affiliations
Abstract

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.

Keywords: COVID‐19; FcgRIIa; MERS‐CoV; SARS‐CoV‐2; antibody‐dependent enhancement; cross‐reactive antibodies; non‐neutralizing antibodies.

 
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