Durable antibody responses elicited by 1 dose of Ad26.COV2.S and substantial increase after boosting: 2 randomized clinical trials

Jerald Sadoff; Mathieu Le Gars; Boerries Brandenburg; Vicky Cárdenas; Georgi Shukarev; Nathalie Vaissiere; Dirk Heerwegh; Carla Truyers; Anne Marit de Groot; Mandy Jongeneelen; Krisztian Kaszas; Jeroen Tolboom; Gert Scheper; Jenny Hendriks; Javier Ruiz-Guiñazú; Frank Struyf; Johan Van Hoof; Macaya Douoguih; Hanneke Schuitemaker

doi:10.1016/j.vaccine.2022.05.047

Durable antibody responses elicited by 1 dose of Ad26.COV2.S and substantial increase after boosting: 2 randomized clinical trials

Vaccine. 2022 Jul 30;40(32):4403-4411. doi: 10.1016/j.vaccine.2022.05.047. Epub 2022 Jun 3.

Authors

Jerald Sadoff¹, Mathieu Le Gars², Boerries Brandenburg², Vicky Cárdenas³, Georgi Shukarev², Nathalie Vaissiere⁴, Dirk Heerwegh⁴, Carla Truyers⁴, Anne Marit de Groot², Mandy Jongeneelen², Krisztian Kaszas², Jeroen Tolboom², Gert Scheper², Jenny Hendriks², Javier Ruiz-Guiñazú⁴, Frank Struyf⁴, Johan Van Hoof², Macaya Douoguih², Hanneke Schuitemaker²

Affiliations

¹ Janssen Vaccines and Prevention, Leiden, The Netherlands. Electronic address: jsadoff@its.jnj.com.
² Janssen Vaccines and Prevention, Leiden, The Netherlands.
³ Janssen Research and Development, Spring House, PA, USA.
⁴ Janssen Research and Development, Beerse, Belgium.

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 × 10¹⁰ viral particles [vp]) followed by booster doses of 5 × 10¹⁰ vp or 1.25 × 10¹⁰ 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 × 10¹⁰ 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 × 10¹⁰ 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.

Keywords: Ad26.COV2.S; Antibody; COVID-19; Enzyme-linked immunosorbent assay; Vaccine; Virus neutralization assay.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Ad26COVS1*
Antibodies, Neutralizing
Antibodies, Viral
Antibody Formation
COVID-19 Vaccines
COVID-19* / prevention & control
Humans
Randomized Controlled Trials as Topic
SARS-CoV-2

Substances

Ad26COVS1
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines

Supplementary concepts

SARS-CoV-2 variants

Associated data