Neutralizing Antibody Levels as a Correlate of Protection Against <scp>SARS‐CoV</scp>‐2 Infection: A Modeling Analysis
Guillaume Lingas, Delphine Planas, Hélène Péré, Françoise Porrot, Florence Guivel‐Benhassine, Isabelle Staropoli, Darragh Duffy, Nicolas Chapuis, Camille Gobeaux, David Veyer, Constance Delaugerre, Jérôme Le Goff, Prunelle Getten, Jérôme Hadjadj, Adèle Bellino, Béatrice Parfait, Jean‐Marc Tréluyer, Olivier Schwartz, Jérémie Guedj, Solen Kernéis, Benjamin Terrier
Abstract
Although anti‐severe acute respiratory syndrome‐coronavirus 2 antibody kinetics have been described in large populations of vaccinated individuals, we still poorly understand how they evolve during a natural infection and how this impacts viral clearance. For that purpose, we analyzed the kinetics of both viral load and neutralizing antibody levels in a prospective cohort of individuals during acute infection with alpha variant. Using a mathematical model, we show that the progressive increase in neutralizing antibodies leads to a shortening of the half‐life of both infected cells and infectious viral particles. We estimated that the neutralizing activity reached 90% of its maximal level within 11 days after symptom onset and could reduce the half‐life of both infected cells and circulating virus by a 6‐fold factor, thus playing a key role to achieve rapid viral clearance. Using this model, we conducted a simulation study to predict in a more general context the protection conferred by pre‐existing neutralization titers, due to either vaccination or prior infection. We predicted that a neutralizing activity, as measured by 50% effective dose > 10 3 , could reduce by 46% the risk of having viral load detectable by standard polymerase chain reaction assays and by 98% the risk of having viral load above the threshold of infectiousness. Our model shows that neutralizing activity could be used to define correlates of protection against infection and transmission.