Antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers

Multiple studies of vaccinated and convalescent cohorts have demonstrated that serum neutralizing antibody (nAb) titers correlate with protection against coronavirus disease 2019 (COVID-19). However, the induction of multiple layers of immunity after severe acute respiratory syndrome coronavirus 2 (...

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Bibliographic Details
Published in:Science translational medicine 2023-03, Vol.15 (688), p.eadg2783-eadg2783
Main Authors: Schmidt, Pete, Narayan, Kristin, Li, Yong, Kaku, Chengzi I, Brown, Michael E, Champney, Elizabeth, Geoghegan, James C, Vásquez, Maximiliano, Krauland, Eric M, Yockachonis, Thomas, Bai, Shuangyi, Gunn, Bronwyn M, Cammarata, Anthony, Rubino, Christopher M, Ambrose, Paul, Walker, Laura M
Format: Article
Language:English
Subjects:
Adult
Antibodies
Antibodies, Monoclonal - therapeutic use
Antibodies, Neutralizing
Antibodies, Viral
Coronaviruses
COVID-19
COVID-19 vaccines
Humans
Monoclonal antibodies
Pharmacokinetics
Prophylaxis
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Vaccination
Vaccines
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Summary:Multiple studies of vaccinated and convalescent cohorts have demonstrated that serum neutralizing antibody (nAb) titers correlate with protection against coronavirus disease 2019 (COVID-19). However, the induction of multiple layers of immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure has complicated the establishment of nAbs as a mechanistic correlate of protection (CoP) and hindered the definition of a protective nAb threshold. Here, we show that a half-life-extended monoclonal antibody (adintrevimab) provides about 50% protection against symptomatic COVID-19 in SARS-CoV-2-naïve adults at serum nAb titers on the order of 1:30. Vaccine modeling results support a similar 50% protective nAb threshold, suggesting that low titers of serum nAbs protect in both passive antibody prophylaxis and vaccination settings. Extrapolation of adintrevimab pharmacokinetic data suggests that protection against susceptible variants could be maintained for about 3 years. The results provide a benchmark for the selection of next-generation vaccine candidates and support the use of broad, long-acting monoclonal antibodies as alternatives or supplements to vaccination in high-risk populations.
ISSN:1946-6234
1946-6242
1946-3242
DOI:10.1126/scitranslmed.adg2783