Evaluation of the Diagnostic Performance of Two Automated SARS-CoV-2 Neutralization Immunoassays following Two Doses of mRNA, Adenoviral Vector, and Inactivated Whole-Virus Vaccinations in COVID-19 Naive Subjects

Background: Limited data are available on humoral responses determined by automated neutralization tests following the administration of the three different types of COVID-19 vaccinations. Thus, we here evaluated anti-SARS-CoV-2 neutralizing antibody titers via two different neutralization assays in comparison to total spike antibody levels. Methods: Healthy participants (n = 150) were enrolled into three subgroups who were tested 41 (22-65) days after their second dose of mRNA (BNT162b2/mRNA-1273), adenoviral vector (ChAdOx1/Gam-COVID-Vac) and inactivated whole-virus (BBIBP-CorV) vaccines, with no history or serologic evidence of prior SARS-CoV-2 infection. Neutralizing antibody (N-Ab) titers were analyzed on a Snibe Maglumi((R)) 800 instrument and a Medcaptain Immu F6((R)) Analyzer in parallel to anti-SARS-CoV-2 S total antibody (S-Ab) levels (Roche Elecsys((R)) e602). Results: Subjects who were administered mRNA vaccines demonstrated significantly higher SARS-CoV-2 N-Ab and S-Ab levels compared to those who received adenoviral vector and inactivated whole-virus vaccinations (p < 0.0001). N-Ab titers determined by the two methods correlated with each other (r = 0.9608; p < 0.0001) and S-Ab levels (r = 0.9432 and r = 0.9324; p < 0.0001, respectively). Based on N-Ab values, a new optimal threshold of Roche SAb was calculated (166 BAU/mL) for discrimination of seropositivity showing an AUC value of 0.975 (p < 0.0001). Low post-vaccination N-Ab levels (median value of 0.25 mu g/mL or 7.28 AU/mL) were measured in those participants (n = 8) who were infected by SARS-CoV-2 within 6 months after immunizations. Conclusion: Both SARS-CoV-2 N-Ab automated assays are effective to evaluate humoral responses after various COVID-19 vaccines

Automated summary

This study evaluated humoral responses after different types of COVID-19 vaccinations by analyzing anti-SARS-CoV-2 neutralizing antibody titers using two different neutralization assays and comparing them to total spike antibody levels. The results showed that individuals who received mRNA vaccines had significantly higher levels of SARS-CoV-2 neutralizing antibodies and spike antibodies compared to those who received adenoviral vector and inactivated whole-virus vaccines. The neutralizing antibody values can be used to determine seropositivity, and low levels were observed in individuals who were infected with SARS-CoV-2 within 6 months after vaccination.