[Skip to Content]
[Skip to Content Landing]

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

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is the Ad26.COV2.S vaccine immunogenic in humans, how quickly does it raise antibody responses, and what types of immune responses are elicited?

Findings  This randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S enrolled 25 participants. Antibodies were detected in vaccine recipients by day 8 and were observed in all vaccine recipients by day 57 after a single immunization. T-cell responses were also generated in vaccine recipients.

Meaning  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.

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

Sign in to take quiz and track your certificates

Buy This Activity
Our websites may be periodically unavailable between 7:00pm CT December 9, 2023 and 1:00am CT December 10, 2023 for regularly scheduled maintenance.

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Dan H. Barouch, MD, PhD, Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 330 Brookline Ave, E/CLS-1043, Boston, MA 02215 (dbarouch@bidmc.harvard.edu).

Accepted for Publication: February 25, 2021.

Published Online: March 11, 2021. doi:10.1001/jama.2021.3645

Author Contributions: Dr Barouch had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Stephenson, Le Gars, Sadoff, de Groot, Truyers, Jaegle, Struyf, Douoguih, Van Hoof, Schuitemaker, Barouch.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Stephenson, Yu, Li, Jaegle, Kanjilal, Schuitemaker, Barouch.

Critical revision of the manuscript for important intellectual content: Stephenson, Le Gars, Sadoff, de Groot, Heerwegh, Truyers, Atyeo, Loos, Chandrashekar, McMahan, Tostanoski, Gebre, Jacob-Dolan, Patel, Peter, Liu, Borducchi, Nkolola, Souza, Tan, Zash, Julg, Nathavitharana, Shapiro, Abdul Azim, Alonso, Ansel, Guiney, Bradshaw, Tyler, Makoni, Yanosick, Seaman, Lauffenburger, Alter, Struyf, Douoguih, Van Hoof, Schuitemaker, Barouch.

Statistical analysis: Stephenson, Le Gars, Heerwegh, Truyers, Loos, Tostanoski.

Obtained funding: Stephenson, Barouch.

Administrative, technical, or material support: Stephenson, Le Gars, Sadoff, de Groot, Chandrashekar, McMahan, Gebre, Patel, Peter, Liu, Borducchi, Souza, Tan, Julg, Nathavitharana, Abdul Azim, Alonso, Ansel, Kanjilal, Guiney, Bradshaw, Tyler, Makoni, Yanosick, Seaman, Alter.

Supervision: Stephenson, Chandrashekar, Nkolola, Souza, Tan, Julg, Jaegle, Ansel, Lauffenburger, Alter, Struyf, Douoguih, Van Hoof, Schuitemaker, Barouch.

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.

Funding/Support: This study was funded by Janssen Vaccines & Prevention BV, the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, MassCPR, the NIH (CA260476), and BARDA (HHS0100201700018C).

Role of the Funder/Sponsor: The sponsors were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation and review of the manuscript. The sponsors were not involved in the decision to submit the manuscript for publication and did not have the right to veto publication or to control the decision regarding to which journal the paper was submitted.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We thank the participants and staff at the Center for Virology and Vaccine Research Clinical Trials Unit, the Harvard Catalyst Clinical Research Center, and Janssen Vaccines & Prevention.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close