Several studies have reported that, in binding and pseudovirus neutralization assays, exposure to CoVs or vaccination against them induces cross-reactive antibodies, including against the latest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, plasma from the pre-coronavirus disease (COVID-19) pandemic times could not neutralize live SARS-CoV-2.

Occasionally, the results of binding assays are referred to as neutralizing, but the relevance of binding assays is different from the neutralization of viruses by antibodies. For example, recent studies have reported that antibodies against SARS-CoV-2 could bind to seasonal CoVs, and it remains unclear whether these cross-reactive antibodies could neutralize the seasonal CoVs.

Antibody concentrates were prepared from the plasma of SARS-CoV-2-naïve donors (pre-pandemic), plasma from COVID-19-recovered donors (post-COVID), or vaccinated donors (pandemic). The collected plasma specimens were used to prepare immunoglobulin (IG) lots through a licensed process, which were then tested to neutralize SARS-CoV-2 and human CoVs (HCoVs) such as OC43 and NL63. The pre-pandemic and pandemic IG were prepared from the plasma of donors in the United States (US) from April to June 2020 and July to September 2021, respectively. Post-COVID IG was obtained from donors from Austria or the US.

A previously established protocol determined neutralizing antibody (nAb) titers against SARS-CoV-2. Similarly, nAb titers against both HCoVs were evaluated. In brief, the serially diluted (IG) specimens were incubated with either HCoV at 103 median tissue culture infectious dose (TCID50) per milliliter (ml). The cytopathic effect was studied after 9 – 11 days of incubation of HCoV-NL63 on LLC-MK2 cells and 6 – 8 days of HCoV-OC43 on MRC-5 cells. The resultant 50% virus neutralization (µNT50) was estimated using the Spearman-Karber method and subsequently normalized to an internal control. The nAb potency was compared between pre-pandemic, pandemic, and post-COVID IG lots.

From September 2020 to October 2021, about 326 IG lots were prepared and screened for nAbs against SARS-CoV-2 and HCoVs. The IG preparations from September 2020 had a mean nAb titer of 2 IU/ml against SARS-CoV-2, which cross-reactive increased to 4210 IU/ml for IG lots prepared in October 2021. Nevertheless, the nAb titers against HCoVs remained relatively stable during this period.

Neutralization of SARS-CoV-2, HCoV-NL63 and HCoV-OC43 by immunoglobulin (IG) released September 2020 – September 2021 (N=326; 13–31 lots/month). SARS-CoV-2 neutralization was normalized to WHO International Standard 20/136 and reported as international units/milliliter (IU/ml). HCV titers were normalized to an internal standard and reported as µNT50 titer [norm. 1:X]. Shown are geometric mean titer ± 95% confidence intervals.

Neutralization of SARS-CoV-2, HCV-NL63 and HCoV-OC43 by immunoglobulin (IG) released September 2020 – September 2021 (N=326; 13–31 lots/month). SARS-CoV-2 neutralization was normalized to WHO International Standard 20/136 and reported as international units/milliliter (IU/ml). HCV titers were normalized to an internal standard and reported as µNT50 titer [norm. 1:X]. Shown are geometric mean titer ± 95% confidence intervals.

Consistent with several other reports, the authors did not observe SARS-CoV-2 neutralization by IG preparations from plasma of pre-pandemic donors. Although post-COVID IG lots potently neutralized SARS-CoV-2, IG preparations from vaccinated donors were nearly 4-fold more potent. The pre-pandemic IG neutralized HCoVs with high potency.

In contrast, post-COVID and pandemic IG lots significantly and potently neutralized SARS-CoV-2. The neutralizing activity of post-COVID and pandemic IG against HCoVs was comparable to that of pre-pandemic IG lots.

Source: This news is originally published by news-medical

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