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Clinical Trial
. 2021 Apr 20;325(15):1535-1544.
doi: 10.1001/jama.2021.3645.

Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19

Kathryn E Stephenson  1   2   3 , Mathieu Le Gars  4 , Jerald Sadoff  4 , Anne Marit de Groot  4 , Dirk Heerwegh  5 , Carla Truyers  5 , Caroline Atyeo  2   6 , Carolin Loos  2   7 , Abishek Chandrashekar  1 , Katherine McMahan  1 , Lisa H Tostanoski  1 , Jingyou Yu  1 , Makda S Gebre  1   6 , Catherine Jacob-Dolan  1   6 , Zhenfeng Li  1 , Shivani Patel  1 , Lauren Peter  1 , Jinyan Liu  1 , Erica N Borducchi  1 , Joseph P Nkolola  1 , Morgana Souza  1 , Chen Sabrina Tan  1   3 , Rebecca Zash  1   3 , Boris Julg  1   2 , Ruvandhi R Nathavitharana  3 , Roger L Shapiro  3 , Ahmed Abdul Azim  3 , Carolyn D Alonso  3 , Kate Jaegle  1 , Jessica L Ansel  1 , Diane G Kanjilal  1 , Caitlin J Guiney  1 , Connor Bradshaw  1 , Anna Tyler  1 , Tatenda Makoni  1 , Katherine E Yanosick  1 , Michael S Seaman  1 , Douglas A Lauffenburger  7 , Galit Alter  2 , Frank Struyf  5 , Macaya Douoguih  4 , Johan Van Hoof  4 , Hanneke Schuitemaker  4 , Dan H Barouch  1   2   3   6   8
Affiliations
Clinical Trial

Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19

Kathryn E Stephenson et al. JAMA. .

Abstract

Importance: Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines.

Objective: To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses.

Design, setting, and participants: Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S.

Interventions: Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 1010 viral particles or 1 × 1011 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group).

Main outcomes and measures: Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses.

Results: Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced.

Conclusion and relevance: In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine.

Trial registration: ClinicalTrials.gov Identifier: NCT04436276.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Stephenson reported receiving grants from the National Institutes of Health (NIH), Gilead, and Regeneron during the conduct of the study. Dr Le Gars reported receiving grants from the Biomedical Advanced Research and Development Authority (BARDA) during the conduct of the study, being an employee of Janssen Pharmaceuticals, and being a coinventor on related vaccine patents. Dr Sadoff reported receiving grants from BARDA , being an employee of Janssen, and having a patent for a COVID-19 vaccine pending, assigned to Janssen. Dr de Groot reported receiving grants from BARDA during the conduct of the study, being an employee of Janssen Infectious Diseases and Vaccines, and being coinventor on related vaccine patents. Dr Heerwegh reported receiving grants from Janssen Vaccines & Prevention during the conduct of the study; receiving personal fees from Janssen Vaccines & Prevention and restricted shares from Janssen Vaccines & Prevention outside the submitted work; and being coinventor on related vaccine patents. Dr Truyers reported receiving grants from BARDA for Ad26 COVID-19 vaccine development and being an employee of Johnson & Johnson. Dr Nkolola reported receiving contracted assignments from Janssen Vaccines & Prevention BV and grants from the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH, and BARDA during the conduct of the study. Dr Alonso reported receiving grants from Merck during the conduct of the study. Dr Alter reported being cofounder and consultant of Seromyx Systems Inc; receiving grants from Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Merck, Gilead, Novavax, Janssen, Sanofi, and the Bill and Melinda Gates Foundation outside the submitted work; and having a patent for Systems Serology Platform pending. Dr Struyf reported receiving grants from Janssen R&D during the conduct of the study ,being an employee of Janssen R&D, and being coinventor on related vaccine patents. Dr Douoguih reported receiving grants from BARDA during the conduct of the study, being an employee of Janssen, receiving company stocks outside the submitted work, and being coinventor on related vaccine patents. Dr Van Hoof reported being an employee of Janssen Pharmaceuticals and coinventor on related vaccine patents. Dr Schuitemaker reported receiving grants from BARDA during the conduct of the study, receiving personal fees from Janssen Vaccines & Prevention BV and Johnson & Johnson outside the submitted work, and being coinventor on related vaccine patents. Dr Barouch reported receiving grants from Janssen during the conduct of the study and grants from the NIH, Henry M. Jackson Foundation/Walter Reed Army Institute of Research, the Bill and Melinda Gates Foundation, Defense Advanced Research Projects Agency, Gilead, Intima, Alkermes, CureVac, South Africa Medical Research Council, amfAR, Ragon Institute, MassCPR, Sanofi, Legend, and Zentalis and personal fees from SQZ Biotech outside the submitted work; in addition, Dr Barouch had a patent for COVID-19 vaccines pending (no premarket royalties or payments of any kind from Janssen). No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Recruitment, Randomization, and Follow-up in a Study of Ad26.COV2.S Vaccine
BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); PCR, polymerase chain reaction; and vp, viral particles.
Figure 2.
Figure 2.. Kinetics and Magnitude of Binding and Neutralizing Antibodies (NAb) Following Ad26.COV2.S Vaccination
Spike- and receptor binding domain (RBD)–specific binding antibodies by enzyme-linked immunosorbent assay (ELISA) (A and B) and SARS-CoV-2 pseudovirus neutralizing antibody (psVNA) and Ad26 virus neutralizing antibody (Ad26 VNA) (C and D) responses following Ad26.COV2.S vaccination. Symbols represent different dosing groups postprime and postboost. The red bars indicate geometric mean titers and the dotted lines indicate lower limits of quantitation (LLOQ).
Figure 3.
Figure 3.. Systems Serology Following Ad26.COV2.S Vaccination
Polar plots showing the diversity of induced SARS-CoV-2 antibody characteristics and functions. The mean percentile of the spike- and receptor binding domain (RBD)–specific antibody features in each group are shown on day 29. Distance from the origin reflects the effect size. Each wedge represents a SARS-CoV-2 antibody feature, and the size of the wedge indicates the magnitude of the value. The colors represent the type of feature: orange, antibody Ig isotypes and subclasses; gray, Fc receptor (FcR) binding levels; and blue, antibody functions including antibody-dependent complement deposition (ADCD), antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent NK cell activation (ADNKA).
Figure 4.
Figure 4.. Antibody Cross-Reactivity Following Ad26.COV2.S Vaccination
Electrochemiluminescence assay (Meso Scale Discovery SARS-CoV-2 IgG Panel 2; K15369U-2) assessing binding antibody responses to the spike proteins from SARS-CoV-2 and SARS-CoV-1 following Ad26.COV2.S vaccination. The red bars indicate geometric mean responses.
Figure 5.
Figure 5.. Kinetics and Magnitude of Cellular Immune Responses Following Ad26.COV2.S Vaccination
Interferon (IFN)-γ and IL-4 enzyme-linked immunospot (ELISPOT) responses to assess TH1 and TH2 cellular immune responses (A and B) and IFN-γ central memory (CM) CD27+/CD45RA-/CD4+ and CD8+ T-cell responses by intracellular cytokine staining (ICS) assays (C) following Ad26.COV2.S vaccination. ICS assays were performed in a subset of participants with sufficient peripheral blood mononuclear cells (PBMCs) on days 71 and 85. The red bars indicate geometric mean responses.
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