Durability of antibody responses elicited by a single dose of Ad26.COV2.S and substantial increase following late boosting

Sadoff, J.; Le Gars, M.; Cardenas, V.; Shukarev, G.; Vaissiere, N.; Heerwegh, D.; Truyers, C.; de Groot, A. M.; Scheper, G.; Hendriks, J.; Ruiz-Guinazu, J.; Struyf, F.; Van Hoof, J.; Douoguih, M.; Schuitemaker, H.

Background: We evaluated the durability of SARS-CoV-2 antibody levels elicited by the single dose Janssen COVID-19 vaccine, Ad26.COV2.S, and the impact on antibody responses of boosting with Ad26.COV2.S after 6 months in clinical trial participants. Methods: Spike-binding antibody and SARS-CoV-2 neutralizing antibody levels elicited by a single-dose Ad26.COV2.S (5x1010 viral particles [vp]) primary regimen and booster doses (5x1010 vp and 1.25x1010 vp) were assessed by ELISA and wild-type VNA in sera from participants in a Phase 1/2a clinical trial (Cohort 1a, 18-55 years old, N=25; Cohort 2a, 18-55 years old boosted at 6 months, N=17; Cohort 3, [≥]65 years old, N=22) and a Phase 2 clinical trial (18-55 and [≥]65-year old participants boosted at 6 months, total N=73). Neutralizing antibody levels were determined approximately 8 months after the primary vaccination in participants aged 18-55 years and approximately 9 months in participants aged [≥]65 years. Binding antibody levels were evaluated 6 months after primary vaccination and 7- and 28-days after booster doses in both age groups. Results: A single dose of Ad26.COV2.S elicited neutralizing antibodies that remained largely stable for approximately 8-9 months and binding antibodies that remained stable for at least 6 months irrespective of age group. A 5x1010 vp booster dose at 6 months post prime vaccination in 18-55-year-old adults elicited a steep and robust 9-fold increase at Day 7 post boost compared to Day 29 levels following the initial immunization. A lower booster dose of 1.25x1010 vp at 6 months in adults 18-55 and [≥]65 years of age also elicited a rapid and high increase of 6-7.7 fold at Day 28 post boost compared to Day 29 levels following the initial immunization, with similar magnitude of post-boost responses in both age groups. Conclusions: A single dose of Ad26.COV2.S, which demonstrated protection in a Phase 3 efficacy trial, elicited durable neutralizing and binding antibodies for at least 8 and 6 months, respectively, in adults >18 years of age at levels similar to Day 29 responses. A 5x1010 vp or 1.25x1010 vp booster dose at 6 months elicited rapid and robust increases in spike binding antibody levels. The anamnestic responses after booster immunization imply robust immune memory elicited by single-dose Ad26.COV2.S.