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Primary, Recall, and Decay Kinetics of SARS-CoV-2 Vaccine Antibody Responses.

Ibarrondo FJ, Hofmann C, Fulcher JA, Goodman-Meza D, Mu W, Hausner MA, Ali A, Balamurugan A, Taus E, Elliott J, Krogstad P, Tobin NH, Ferbas KG, Kitchen SG, Aldrovandi GM, Rimoin AW, Yang OO. Primary, Recall, and Decay Kinetics of SARS-CoV-2 Vaccine Antibody Responses. ACS nano. 2021 Jun 23.

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Studies of two SARS-CoV-2 mRNA vaccines suggested that they yield 95% protection from symptomatic infection at least short-term, but important clinical questions remain. It is unclear how vaccine-induced antibody levels quantitatively compare to the wide spectrum induced by natural SARS-CoV-2 infection. Vaccine response kinetics and magnitudes in persons with prior COVID-19 compared to virus-na ve persons are not well-defined. The relative stability of vaccine-induced versus infection-induced antibody levels is unclear. We addressed these issues with longitudinal assessments of vaccinees with and without prior SARS-CoV-2 infection using quantitative enzyme-linked immunosorbent assay (ELISA) of anti-RBD antibodies. SARS-CoV-2-na ve individuals achieved levels similar to mild natural infection after the first vaccination; a second dose generated levels approaching severe natural infection. In persons with prior COVID-19, one dose boosted levels to the high end of severe natural infection even in those who never had robust responses from infection, increasing no further after the second dose. Antiviral neutralizing assessments using a spike-pseudovirus assay revealed that virus-na ve vaccinees did not develop physiologic neutralizing potency until the second dose, while previously infected persons exhibited maximal neutralization after one dose. Finally, antibodies from vaccination waned similarly to natural infection, resulting in an average of 90% loss within 90 days. In summary, our findings suggest that two doses are important for quantity and quality of humoral immunity in SARS-CoV-2-na ve persons, while a single dose has maximal effects in those with past infection. Antibodies from vaccination wane with kinetics very similar to that seen after mild natural infection; booster vaccinations will likely be required.

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