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

Thomas, Swapna; Smatti, Maria K.; Alsulaiti, Haya; Zedan, Hadeel T.; Eid, Ali H.; Hssain, Ali A.; Abu Raddad, Laith J.; Gentilcore, Giusy; Ouhtit, Allal; Althani, Asmaa A.; Nasrallah, Gheyath K.; Grivel, Jean‐Charles; Yassine, Hadi M.

doi:10.1002/jmv.29628

Cited by 2 publications

(1 citation statement)

References 45 publications

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“…The immunization of monkeys with three doses of MultiTEP-RBD471-493 with AdvaxCpG adjuvant induced high IgG binding titers but low sVNT and pVNT titers. Indeed, there are published data by others suggesting antibody-dependent enhancement (ADE) at high serum concentrations, a phenomenon seen in the presence of predominantly non-neutralizing antibodies [ 45 , 46 ]. However, it is important to note that ADE has not been conclusively demonstrated in vivo for this particular context.…”

Section: Discussionmentioning

confidence: 99%

MultiTEP-Based Vaccines Targeting SARS-CoV-2 Spike Protein IgG Epitopes Elicit Robust Binding Antibody Titers with Limited Virus-Neutralizing Activity

Antonyan,

Chilingaryan,

Zagorski

et al. 2024

Pathogens

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Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The disruptions caused by the pandemic underscore the need for a universal vaccine against respiratory betacoronaviruses. Our group previously developed the universal platform for vaccine development, MultiTEP, which has been utilized in this study to generate a range of SARS-CoV-2 epitope vaccine candidates. We prepared and characterized 18 vaccines incorporating small peptide fragments from SARS-CoV-2 Spike protein fused with the MultiTEP sequence using overlapping PCR. Wild-type mice were immunized intramuscularly with the immunogen formulated in AdvaxCpG adjuvant. Serum antibodies were detected by ELISA, surrogate neutralization, and pseudovirus neutralization assays. Finally, the most promising vaccine candidate was administered to three non-human primates. All vaccines generated high titers of spike-binding IgG antibodies. However, only three vaccines generated antibodies that blocked RBD binding to the ACE2 receptor in a surrogate virus neutralization assay. However, none of the vaccines induced antibodies able to neutralize pseudotype viruses, including after the administration of the lead vaccine to NHPs. MultiTEP-based COVID-19 vaccines elicited robust, IgG-binding responses against the Spike protein in mice and non-human primates, but these antibodies were not neutralizing, underscoring the need to refine this approach further.

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Section: Discussionmentioning

confidence: 99%

MultiTEP-Based Vaccines Targeting SARS-CoV-2 Spike Protein IgG Epitopes Elicit Robust Binding Antibody Titers with Limited Virus-Neutralizing Activity

Antonyan,

Chilingaryan,

Zagorski

et al. 2024

Pathogens

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Enhanced Assessment of Cross-Reactive Antigenic Determinants within the Spike Protein

Lechuga,

Temerozo,

Napoleão-Pêgo

et al. 2024

IJMS

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Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses regarding SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear B-cell epitopes in its spike glycoprotein with an SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. The bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), which was confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA for anti-SARS-CoV-2 antibodies. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infections of monocytes was observed in vitro with pre-pandemic Dengue-positive sera. A significant increase in viral load was measured compared to that of the controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. Cross-reactivity against peptides from spike proteins was observed for the pre-pandemic sera. This study highlights the importance of identifying specific epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future infections on diseases and their impact on vaccinations and immunodiagnostics.

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

Cited by 2 publications

References 45 publications

MultiTEP-Based Vaccines Targeting SARS-CoV-2 Spike Protein IgG Epitopes Elicit Robust Binding Antibody Titers with Limited Virus-Neutralizing Activity

MultiTEP-Based Vaccines Targeting SARS-CoV-2 Spike Protein IgG Epitopes Elicit Robust Binding Antibody Titers with Limited Virus-Neutralizing Activity

Enhanced Assessment of Cross-Reactive Antigenic Determinants within the Spike Protein

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