SUMMARY

• The Janssen COVID-19 Vaccine has been granted an Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA). The Janssen COVID-19 Vaccine has not been approved or licensed by FDA, but has been authorized for emergency use by FDA, under an EUA for active immunization to prevent Coronavirus Disease 2019 (COVID-19) in individuals 18 years of age and older for whom other FDA-authorized or approved COVID-19 vaccines are not accessible or clinically appropriate, and in individuals 18 years of age and older who elect to receive the Janssen COVID-19 Vaccine because they would otherwise not receive a COVID-19 vaccine. The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of the medical product under Section 564(b)(1) of the Federal Food, Drug, and Cosmetic Act unless the declaration is terminated or authorization revoked sooner.^{1, 2}
• The Janssen COVID-19 Vaccine is a viral vector vaccine that utilizes Janssen’s proprietary AdVac^® and PER.C6^® technologies.³
  • AdVac is based on the development and production of adenovirus vectors (gene carriers). It can be used together with PER.C6 technology to develop recombinant vaccines against life-threatening infectious diseases.
  • PER.C6 provides a manufacturing system for high-yield, faster and large-scale production of vaccines and monoclonal antibodies. It is especially useful for vaccine manufacturing that requires the production of hard-to-grow viruses.
• AdVac uses an adenovirus as a vector (a carrier) of the genetic code of an antigen (SARS-CoV-2 antigen) called the spike protein and then manufactured for large-scale production through PER.C6. After the Janssen COVID-19 Vaccine is injected, the SARS-CoV-2 antigen triggers production of antibodies and a resulting immune response. The vaccine does not cause infection with either COVID-19 or the adenovirus that is used as the vector. Additionally, the genetic material delivered by the viral vector does not integrate into a person’s deoxyribonucleic acid (DNA).^4-6
• The Janssen COVID-19 Vaccine is not a live virus vaccine.⁷
• For additional information on Janssen’s AdVac and PER.C6 technologies, please visit: https://www.janssen.com/infectious-diseases-and-vaccines/vaccine-technology and https://www.janssen.com/emea/emea/janssen-vaccine-technologies.
• For general information on COVID-19 viral vector vaccines, please visit: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/viralvector.html.

BACKGROUND

AdVac Platform

Ad26.COV2.S is a monovalent vaccine composed of a recombinant, replication-incompetent human Ad26 vector, constructed to encode the SARS-CoV-2 S protein sequence (from the isolate Wuhan-Hu-1, GenBank accession number: MN908947), stabilized in its prefusion conformation.⁸

Adenoviruses are nonenveloped viruses composed of an icosahedral nucleocapsid and a single double-stranded linear DNA genome. There are at least 88 human adenovirus types⁹, divided into subgroups A-G based on neutralization by antisera, and genotyping.⁸

Recombinant, replication-incompetent adenoviral vectors are attractive candidates for expression of foreign genes for a number of reasons. The viral vector is replication incompetent so the viral DNA cannot replicate and will over time be cleared from the cells/tissues, e.g. due to cell division, or due to removal of transduced cells by the immune system. Viral vector DNA can be detected in tissues at very low levels for weeks until a few months after vaccination in animal models. Antigen expression data for the S protein are not available, but in animals the expression of another antigen delivered with the Ad26 vector cannot be detected after 1-2 weeks.¹⁰ The adenoviral genome is well characterized and comparatively easy to manipulate. Adenoviruses exhibit broad tropism, infecting a variety of dividing and non-dividing cells. The adenoviral vaccine (AdVac) vector platform allows for high-yield production of replication-incompetent adenovirus vectors. The adenovirus E1 region is deleted to render the vector replication-incompetent and create space for transgenes, with viral replication taking place in cells that complement for the E1 deletion in the virus genome.¹¹

Janssen selected Ad26 as the vector for the COVID-19 vaccine because of the substantial nonclinical and clinical evidence from Janssen’s other vaccine development programs that also make use of Ad26. Participants, including people from different age groups (elderly, children and infants), human immunodeficiency virus (HIV)-positive individuals, pregnant and breast-feeding women, have been vaccinated with Ad26-based vaccines in several completed and ongoing clinical studies and vaccination programs, revealing a favorable safety profile. Across programs, Ad26-based vaccines demonstrate the capacity to elicit strong humoral immune responses with both neutralizing activity and non-neutralizing antibody functionalities, and cellular immune responses involving both CD8+ T cells and CD4+ T cells, the latter with predominantly a T helper 1 (TH1) phenotype, irrespective of the transgene encoded immunogens.^{8, 12-22}

In July 2020, the first Ad26-based vaccine was granted Marketing Authorization in Europe by the European Commission. Zabdeno^® (Ad26.ZEBOV), as part of the Zabdeno, Mvabea vaccine regimen, was authorized under exceptional circumstances for active immunization for prevention of disease caused by Ebola virus (Zaire ebolavirus species) in individuals ≥1 year of age.^{8, 23}

To date, no consistent pattern of obvious impact of baseline Ad26 neutralizing antibodies on immune responses elicited by Ad26-based vaccines has been observed. Data obtained with Janssen’s Ad26-based Zika-, HIV-, and COVID-19 vaccine candidates demonstrate the ability to increase the immune response elicited by the first dose with subsequent doses of the same Ad26-based vaccine.^{14, 15, 19, 24-26} In addition, data from the Ad26-based Zika vaccine candidate and from the respiratory syncytial virus (RSV) vaccine candidate development programs demonstrate the ability of Ad26-based vaccines to induce a durable immune response up to at least 1 year and 2 years post-vaccination, respectively.^{8, 25}

PER.C6 Cell Line

The PER.C6 cell line is used in the production of adenovirus vectors. Derived from human embryonic retinal cells, PER.C6 has been successfully used in Good Manufacturing Practices (GMP) and grow to high densities in serum-free suspension culture.^{10, 27}

Ad26 vectored COVID-19 vaccine encoding the SARS-CoV-2 spike (S) protein is produced in the PER.C6 TetR Cell Line and by recombinant DNA technology.²⁸

Literature Search

A literature search of Ovid MEDLINE^®, EMBASE^®, BIOSIS^®, and DERWENT databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 06 July 2022.