tetano
Editor, Senior Moderator
Front Immunol
. 2022 Jan 11;12:813240.
doi: 10.3389/fimmu.2021.813240. eCollection 2021.
Two Opposing Roles of SARS-CoV-2 RBD-Reactive Antibodies in Pre-Pandemic Plasma Samples From Elderly People in ACE2-Mediated Pseudovirus Infection
Kyu-Young Sim[SUP] 1 2 [/SUP], Gwang-Hoon Ko[SUP] 2 [/SUP], So-Eun Bae[SUP] 1 [/SUP], Kyu Yeong Choi[SUP] 3 [/SUP], Jung Sup Lee[SUP] 3 4 5 [/SUP], Byeong C Kim[SUP] 3 6 [/SUP], Kun Ho Lee[SUP] 3 5 7 [/SUP], Mi-Ryoung Song[SUP] 2 [/SUP], Sung-Gyoo Park[SUP] 1 [/SUP]
Affiliations
Abstract
A novel coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged and caused an outbreak of unusual viral pneumonia. Several reports have shown that cross-reactive antibodies against SARS-CoV-2 also exist in people unexposed to this virus. However, the neutralizing activity of cross-reactive antibodies is controversial. Here, we subjected plasma samples from SARS-CoV-2-unexposed elderly Korean people (n = 119) to bead-based IgG antibody analysis. SARS-CoV-2 S1 subunit-reactive IgG antibody analysis detected positive signals in some samples (59 of 119, 49.6%). SARS-CoV-2 receptor-binding domain (RBD)-reactive antibody levels were most significantly correlated with human coronavirus-HKU1 S1 subunit-reactive antibody levels. To check the neutralizing activity of plasma samples, the SARS-CoV-2 spike pseudotype neutralizing assay was used. However, the levels of cross-reactive antibodies did not correlate with neutralizing activity. Instead, SARS-CoV-2 pseudovirus infection was neutralized by some RBD-reactive plasma samples (n = 9, neutralization ≥ 25%, P ≤ 0.05), but enhanced by other RBD-reactive plasma samples (n = 4, neutralization ≤ -25%, P ≤ 0.05). Interestingly, the blood plasma groups with enhancing and neutralizing effects had high levels of SARS-CoV-2 RBD-reactive antibodies than the plasma group that had no effect. These results suggest that some SARS-CoV-2 RBD-reactive antibodies from pre-pandemic elderly people exert two opposing functions during SARS-CoV-2 pseudovirus infection. In conclusion, preformed RBD-reactive antibodies may have two opposing functions, namely, protecting against and enhancing viral infection. Analysis of the epitopes of preformed antibodies will be useful to elucidate the underlying mechanism.
Keywords: SARS-CoV-2; cross-reactive antibodies; neutralizing activity; pre-pandemic samples; receptor binding domain (RBD).
. 2022 Jan 11;12:813240.
doi: 10.3389/fimmu.2021.813240. eCollection 2021.
Two Opposing Roles of SARS-CoV-2 RBD-Reactive Antibodies in Pre-Pandemic Plasma Samples From Elderly People in ACE2-Mediated Pseudovirus Infection
Kyu-Young Sim[SUP] 1 2 [/SUP], Gwang-Hoon Ko[SUP] 2 [/SUP], So-Eun Bae[SUP] 1 [/SUP], Kyu Yeong Choi[SUP] 3 [/SUP], Jung Sup Lee[SUP] 3 4 5 [/SUP], Byeong C Kim[SUP] 3 6 [/SUP], Kun Ho Lee[SUP] 3 5 7 [/SUP], Mi-Ryoung Song[SUP] 2 [/SUP], Sung-Gyoo Park[SUP] 1 [/SUP]
Affiliations
- PMID: 35087532
- PMCID: PMC8787138
- DOI: 10.3389/fimmu.2021.813240
Abstract
A novel coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged and caused an outbreak of unusual viral pneumonia. Several reports have shown that cross-reactive antibodies against SARS-CoV-2 also exist in people unexposed to this virus. However, the neutralizing activity of cross-reactive antibodies is controversial. Here, we subjected plasma samples from SARS-CoV-2-unexposed elderly Korean people (n = 119) to bead-based IgG antibody analysis. SARS-CoV-2 S1 subunit-reactive IgG antibody analysis detected positive signals in some samples (59 of 119, 49.6%). SARS-CoV-2 receptor-binding domain (RBD)-reactive antibody levels were most significantly correlated with human coronavirus-HKU1 S1 subunit-reactive antibody levels. To check the neutralizing activity of plasma samples, the SARS-CoV-2 spike pseudotype neutralizing assay was used. However, the levels of cross-reactive antibodies did not correlate with neutralizing activity. Instead, SARS-CoV-2 pseudovirus infection was neutralized by some RBD-reactive plasma samples (n = 9, neutralization ≥ 25%, P ≤ 0.05), but enhanced by other RBD-reactive plasma samples (n = 4, neutralization ≤ -25%, P ≤ 0.05). Interestingly, the blood plasma groups with enhancing and neutralizing effects had high levels of SARS-CoV-2 RBD-reactive antibodies than the plasma group that had no effect. These results suggest that some SARS-CoV-2 RBD-reactive antibodies from pre-pandemic elderly people exert two opposing functions during SARS-CoV-2 pseudovirus infection. In conclusion, preformed RBD-reactive antibodies may have two opposing functions, namely, protecting against and enhancing viral infection. Analysis of the epitopes of preformed antibodies will be useful to elucidate the underlying mechanism.
Keywords: SARS-CoV-2; cross-reactive antibodies; neutralizing activity; pre-pandemic samples; receptor binding domain (RBD).