Durable Antibody Responses Elicited by 1 Dose of Ad26.COV2.S and Substantial Increase After Boosting: 2 Randomized Clinical Trials

Overview

Journal Vaccine

Specialty Allergy & Immunology

Date 2022 Jun 6

PMID 35667914

Authors

Jerald Sadoff

Mathieu Le Gars

Boerries Brandenburg

Vicky Cardenas

Georgi Shukarev

Nathalie Vaissiere

Dirk Heerwegh

Carla Truyers

Anne Marit de Groot

Mandy Jongeneelen

Krisztian Kaszas

Jeroen Tolboom

Gert Scheper

Jenny Hendriks

Javier Ruiz-Guinazu

Frank Struyf

Johan Van Hoof

Macaya Douoguih

Hanneke Schuitemaker

Affiliations

Soon will be listed here.

Abstract

Background: Ad26.COV2.S is a well-tolerated and effective vaccine against COVID-19. We evaluated durability of anti-SARS-CoV-2 antibodies elicited by single-dose Ad26.COV2.S and the impact of boosting.

Methods: In randomized, double-blind, placebo-controlled, phase 1/2a and phase 2 trials, participants received single-dose Ad26.COV2.S (5 × 10 viral particles [vp]) followed by booster doses of 5 × 10 vp or 1.25 × 10 vp. Neutralizing antibody levels were determined by a virus neutralization assay (VNA) approximately 8-9 months after dose 1. Binding and neutralizing antibody levels were evaluated by an enzyme-linked immunosorbent assay and pseudotyped VNA 6 months after dose 1 and 7 and 28 days after boosting.

Results: Data were analyzed from phase 1/2a participants enrolled from 22 July-18 December 2020 (Cohort 1a, 18-55 years [y], N = 25; Cohort 2a, 18-55y, N = 17; Cohort 3, ≥65y, N = 22), and phase 2 participants from 14 to 22 September 2020 (18-55y and ≥ 65y, N = 73). Single-dose Ad26.COV2.S elicited stable neutralizing antibodies for at least 8-9 months and stable binding antibodies for at least 6 months, irrespective of age. A 5 × 10 vp 2-month booster dose increased binding antibodies by 4.9- to 6.2-fold 14 days post-boost versus 28 days after initial immunization. A 6-month booster elicited a steep and robust 9-fold increase in binding antibody levels 7 days post-boost. A 5.0-fold increase in neutralizing antibodies was observed by 28 days post-boost for the Beta variant. A 1.25 × 10 vp 6-month booster elicited a 3.6-fold increase in binding antibody levels at 7 days post-boost versus pre-boost, with a similar magnitude of post-boost responses in both age groups.

Conclusions: Single-dose Ad26.COV2.S elicited durable antibody responses for at least 8 months and elicited immune memory. Booster-elicited binding and neutralizing antibody responses were rapid and robust, even with a quarter vaccine dose, and stronger with a longer interval since primary vaccination.

Trial Registration: ClinicalTrials.gov Identifier: NCT04436276, NCT04535453.

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