| Autor: |
Bastard, Paul, Vazquez, Sara E., Liu, Jamin, Laurie, Matthew T., Wang, Chung Yu, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Zamecnik, Colin, Philippot, Quentin, Rosain, Jérémie, Catherinot, Emilie, Willmore, Andrew, Mitchell, Anthea M., Bair, Rebecca, Garçon, Pierre, Kenney, Heather, Fekkar, Arnaud, Salagianni, Maria, Poulakou, Garyphallia |
| Předmět: |
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| Zdroj: |
Science Immunology; 2023, Vol. 8 Issue 90, p1-14, 14p |
| Abstrakt: |
Life-threatening "breakthrough" cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population. Editor's summary: Autoantibodies that neutralize type I IFNs can cause severe COVID-19 infection, but it is unclear how this applies to SARS-CoV-2 vaccinated individuals. Here, Bastard et al. tested for the presence of antibodies neutralizing SARS-CoV-2 and type I IFN autoantibodies in 48 patients with two mRNA SARS-CoV-2 vaccine doses who experienced severe breakthrough infection. They found that about 20% of these patients had type I IFN autoantibodies and SARS-CoV-2 neutralizing antibodies. Thus, these findings suggest that the presence of type I IFN autoantibodies in SARS-CoV-2 vaccinated individuals correlates with severe infection and might present a druggable target to prevent severe breakthrough infection. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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