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

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-naı̈ve
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-naı̈ve
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-naı̈ve
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-naı̈ve 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.