Immunogenicity of the Ad26.COV2.S COVID-19 Vaccine | Vaccination | JN Learning | AMA Ed Hub [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

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 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

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.

References
1.
Abbink  P , Lemckert  AA , Ewald  BA ,  et al.  Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D.   J Virol. 2007;81(9):4654-4663. doi:10.1128/JVI.02696-06PubMedGoogle ScholarCrossref
2.
Wrapp  D , Wang  N , Corbett  KS ,  et al.  Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.   Science. 2020;367(6483):1260-1263. doi:10.1126/science.abb2507PubMedGoogle ScholarCrossref
3.
Bos  R , Rutten  L , van der Lubbe  JEM ,  et al.  Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses.   NPJ Vaccines. 2020;5:91. doi:10.1038/s41541-020-00243-xPubMedGoogle ScholarCrossref
4.
Tostanoski  LH , Wegmann  F , Martinot  AJ ,  et al.  Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters.   Nat Med. 2020;26(11):1694-1700. doi:10.1038/s41591-020-1070-6PubMedGoogle ScholarCrossref
5.
Mercado  NB , Zahn  R , Wegmann  F ,  et al.  Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques.   Nature. 2020;586(7830):583-588. doi:10.1038/s41586-020-2607-zPubMedGoogle ScholarCrossref
6.
Sadoff  J , Le Gars  M , Shukarev  G ,  et al.  Interim results of a phase 1-2a trial of Ad26.COV2.S COVID-19 vaccine.   N Engl J Med. 2021. doi:10.1056/NEJMoa2034201PubMedGoogle Scholar
7.
Chandrashekar  A , Liu  J , Martinot  AJ ,  et al.  SARS-CoV-2 infection protects against rechallenge in rhesus macaques.   Science. 2020;369(6505):812-817. doi:10.1126/science.abc4776PubMedGoogle ScholarCrossref
8.
Yu  J , Tostanoski  LH , Peter  L ,  et al.  DNA vaccine protection against SARS-CoV-2 in rhesus macaques.   Science. 2020;369(6505):806-811. doi:10.1126/science.abc6284PubMedGoogle ScholarCrossref
9.
Chung  AW , Kumar  MP , Arnold  KB ,  et al.  Dissecting polyclonal vaccine-induced humoral immunity against HIV using systems serology.   Cell. 2015;163(4):988-998. doi:10.1016/j.cell.2015.10.027PubMedGoogle ScholarCrossref
10.
Walsh  EE , Frenck  RW  Jr , Falsey  AR ,  et al.  Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates.   N Engl J Med. 2020;383(25):2439-2450. doi:10.1056/NEJMoa2027906PubMedGoogle ScholarCrossref
11.
Widge  AT , Rouphael  NG , Jackson  LA ,  et al; mRNA-1273 Study Group.  Durability of responses after SARS-CoV-2 mRNA-1273 vaccination.   N Engl J Med. 2021;384(1):80-82.PubMedGoogle ScholarCrossref
12.
Anderson  EJ , Rouphael  NG , Widge  AT ,  et al; mRNA-1273 Study Group.  Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults.   N Engl J Med. 2020;383(25):2427-2438. doi:10.1056/NEJMoa2028436PubMedGoogle ScholarCrossref
13.
Jackson  LA , Anderson  EJ , Rouphael  NG ,  et al; mRNA-1273 Study Group.  An mRNA vaccine against SARS-CoV-2: preliminary report.   N Engl J Med. 2020;383(20):1920-1931. doi:10.1056/NEJMoa2022483PubMedGoogle ScholarCrossref
14.
Folegatti  PM , Ewer  KJ , Aley  PK ,  et al; Oxford COVID Vaccine Trial Group.  Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.   Lancet. 2020;396(10249):467-478. doi:10.1016/S0140-6736(20)31604-4PubMedGoogle ScholarCrossref
15.
Ramasamy  MN , Minassian  AM , Ewer  KJ ,  et al; Oxford COVID Vaccine Trial Group.  Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.   Lancet. 2021;396(10267):1979-1993. doi:10.1016/S0140-6736(20)32466-1PubMedGoogle ScholarCrossref
16.
Logunov  DY , Dolzhikova  IV , Zubkova  OV ,  et al.  Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia.   Lancet. 2020;396(10255):887-897. doi:10.1016/S0140-6736(20)31866-3PubMedGoogle ScholarCrossref
17.
Zhu  FC , Guan  XH , Li  YH ,  et al.  Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial.   Lancet. 2020;396(10249):479-488. doi:10.1016/S0140-6736(20)31605-6PubMedGoogle ScholarCrossref
18.
Zhu  FC , Li  YH , Guan  XH ,  et al.  Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial.   Lancet. 2020;395(10240):1845-1854. doi:10.1016/S0140-6736(20)31208-3PubMedGoogle ScholarCrossref
19.
Keech  C , Albert  G , Cho  I ,  et al.  Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine.   N Engl J Med. 2020;383(24):2320-2332. doi:10.1056/NEJMoa2026920PubMedGoogle ScholarCrossref
20.
Baden  LR , El Sahly  HM , Essink  B ,  et al; COVE Study Group.  Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.   N Engl J Med. 2021;384(5):403-416.PubMedGoogle ScholarCrossref
21.
Polack  FP , Thomas  SJ , Kitchin  N ,  et al; C4591001 Clinical Trial Group.  Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine.   N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577PubMedGoogle ScholarCrossref
22.
Voysey  M , Clemens  SAC , Madhi  SA ,  et al; Oxford COVID Vaccine Trial Group.  Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.   Lancet. 2021;397(10269):99-111.PubMedGoogle ScholarCrossref
23.
McMahan  K , Yu  J , Mercado  NB ,  et al.  Correlates of protection against SARS-CoV-2 in rhesus macaques.   Nature. 2021;590(7847):630-634.PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
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
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

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