Humoral Immune Correlates Analysis of Four Vaccines Against SARS-CoV-2 in Rhesus Macaques

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Correlates of protection (COP) are crucial for evaluating vaccine efficacy.
• Assessing COP helps understand immune responses to vaccines against SARS-CoV-2.

Purpose of the Study:

• To identify and validate immune markers as correlates of protection against SARS-CoV-2.
• To evaluate the predictive power of immune responses for viral load reduction across different vaccines.

Main Methods:

• 126 Rhesus macaques were randomized to placebo or one of four COVID-19 vaccines (mRNA-1273, Ad26.COV2.S, NVX-CoV2373, CoV2 preS dTM+AS03).
• Immune markers (neutralization assays, electrochemiluminescence immunoassay) and viral load measures (RT-qPCR in swabs and lavage) were assessed.
• Statistical models were used to determine the correlation between immune markers and viral load reduction.

Main Results:

• High correlations were observed between all immune marker measurements (≥0.86) and viral load measurements (≥0.87).
• Immune markers significantly predicted viral load reduction, with adjusted R-squared values up to 0.52.
• Simple models using immune markers explained over 80% of variability in viral load reduction, outperforming models including vaccine dose parameters.

Conclusions:

• Neutralizing titers and antibody binding levels serve as reliable correlates of protection for SARS-CoV-2 vaccines.
• These immune markers effectively predict reduced viral load across diverse vaccine platforms.
• The findings support the use of immune markers for vaccine efficacy assessment and development.