In vivo determination of protective antibody thresholds for SARS-CoV-2 variants using mouse models

ABSTRACTNeutralizing antibody titers have been shown to correlate with immune protection against COVID-19 and can be used to estimate vaccine effectiveness. Numerous studies have explored the relationship between neutralizing antibodies and protection. However, there remains a lack of quantitative data directly assessing the minimum effective protective neutralizing antibody titer in in vivo. In this study, we utilized eight cohorts of participants with diverse immune backgrounds for evaluation of protective antibody response. To precisely assess the lower threshold of neutralizing antibody titers required for effective protection against SARS-CoV-2 infections, we employed plasma adoptive transfer from different cohorts into mice. This study demonstrated that neutralizing titers in the plasma of recipient mice correlated well with those in human donors, and a positive linear correlation was observed between the human and mouse recipients of transferred plasma neutralizing titer. A pseudotyped virus neutralizing titers greater than 7 was identified as the minimum threshold necessary to reduce viral titers in infected mice, establishing a crucial baseline for effective protection. Furthermore, despite the variability in immune backgrounds, these diverse cohorts' plasma exhibited a similar neutralizing antibody threshold necessary for protection. This finding has significant implications for vaccine design and the assessment of immune competence.