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

Abstract

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.

Previous Infection Combined with Vaccination Produces Neutralizing Antibodies with Potency against SARS-CoV-2 Variants

“…It is unclear whether our observation relates to time elapsed after infection as proposed by that report, additional maturation due to vaccination, or both. In contrast to studies showing ongoing affinity maturation, a recent report suggests that potency declines after resolution of infection ( 10 ), suggesting that vaccination has a key role in this phenomenon. Our findings also agree with two other recent reports regarding vaccination after prior COVID-19; both Wang et al ( 11 ) and Goel et al ( 12 ) observed that the resulting antibodies gained breadth of coverage against spike variants.…”

“…Anti-RBD antibodies were evaluated with a quantitative enzyme-linked immunosorbent assay (ELISA) as recently described in detail ( 10 , 15 ). In brief, we utilized a modification of a previously reported ELISA ( 16 – 18 ) against recombinant receptor-binding domain (RBD) protein bound to a 96-well microtiter plate, using secondary goat anti-human IgG-, IgM-, or IgA-horseradish peroxidase-conjugated detector antibodies.…”

Update on COVID-19 vaccines and autoimmune-mediated rheumatic diseases

“…There was an average decline in efficacy of approximately 6% every 2 months [10]. Ibarrondo et al [11] reported that the antibodies developed from vaccination and natural mild infection showed similar characteristics in that their wane was slow but constant. There was an average decline of Reumatologia 2021; 59/4 antibody titers of approximately 90% in 3 months after infection or vaccination.…”

Six‐month longitudinal antibody kinetics of mRNA COVID‐19 vaccines

“…In a recent study a 6-month follow-up on the BNT162b2 vaccine showed that on average, the vaccine efficacy declined by approximately 6% every 2 months. 3 Ibarrondo et al, 4 reported that there was an average decline of antibody titers of approximately 90% in 3 months postinfection or vaccination. Naber et al, 5 reported that BNT162b2 vaccinated individuals demonstrated a significant decline in antibody levels 6 weeks after the second dose.…”