Ad26.COV2.S or JNJ-78436735 is a COVID-19 vaccine candidate developed by Janssen Vaccines, which is part of Johnson & Johnson (J&J) in the Netherlands and Beth Israel Deaconess Medical Center (BIDMC).[1] It is a human adenovirus viral vector vaccine.[2] On January 29, 2021, Janssen announced that it was 66% effective in a one-dose regimen in preventing symptomatic COVID-19, with an 85% efficacy in preventing severe COVID-19.[3][4][5] It can remain stable for an estimated timeframe of two years at -20°C (-4°F). The vaccine can be stored at least for three months in a refrigerator at temperatures of 2-8°C (36°F-46°F).[6]
Vaccine characteristics
The J&J vaccine can remain viable for months in a standard refrigerator.[7] Unlike the Pfizer–BioNTech COVID-19 vaccine and Moderna COVID-19 vaccine that previously received EUAs, the J&J COVID-19 vaccine is a single dose instead of two doses, and does not need to be shipped frozen.[8]
Development
Johnson & Johnson committed over US$1 billion toward the development of a not-for-profit COVID-19 vaccine in partnership with the Biomedical Advanced Research and Development Authority (BARDA) Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS).[9][10] J&J stated that its vaccine project would be "at a not-for-profit level" as the company viewed it as "the fastest and the best way to find all the collaborations in the world to make this happen."[11]
Janssen Vaccines, in partnership with Beth Israel Deaconess Medical Center (BIDMC), is responsible for developing the vaccine candidate, based on the same technology used to make its Ebola vaccine.
Clinical trials
Phase I-II
In June 2020, J&J and the National Institute of Allergy and Infectious Diseases (NIAID) confirmed its intention to start a clinical trials of J&J's vaccine in September 2020, with the possibility of Phase 1/2a human clinical trials starting at an accelerated pace in the second half of July.[12][13][14]
A Phase 1-2a clinical trial started with the recruitment of the first subject on July 15, 2020 and enrolled study participants in Belgium and the US. Interim results published from the Phase 1-2a trial established the safety, reactogenecity and immunogenecity of Ad26.COV2.S.[15][16]
Phase III
A Phase 3 clinical trial called ENSEMBLE started enrollment in September 2020 and completed enrollment on December 17, 2020. It was designed as a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of a single-dose vaccine versus placebo in adults 18 years old and older. Study participants received a single intramuscular injection of Ad26.COV2.S at a dose level of 5×1010 virus particles on Day 1.[17] The trial was paused on October 12, 2020, because a volunteer became ill,[18] but the company said it found no evidence that the vaccine had caused the illness and announced on October 23, 2020 that it would resume the trial.[19][20] On January 29, 2021 Janssen announced safety and efficacy data from an interim analysis of ENSEMBLE trial data, which demonstrated the vaccine was 66% effective at preventing the combined endpoints of moderate and severe COVID-19 at 28 days post-vaccination among all volunteers. The interim analysis was based on 468 cases of symptomatic COVID-19 among 43,783 adult volunteers in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa, and the United States. No deaths related to COVID-19 were reported in the vaccine group, while 5 deaths in the placebo group were related to COVID-19.[6] During the trial, no anaphylaxis was observed in participants.[6]
A second Phase 3 clinical trial called ENSEMBLE 2 started enrollment on November 12, 2020. ENSEMBLE 2 differs from ENSEMBLE in that its study participants will receive two intramuscular (IM) injections of Ad26.COV2.S vaccine, one on Day 1 and the next on Day 57.[21]
Manufacturing
In April 2020, J&J entered a partnership with Catalent who will provide large-scale manufacturing of J&J's vaccine at Catalent's Bloomington, Indiana facility.[22] In July 2020, the partnership was expanded to include Catalent's Anagni, Italy facility.[23]
In July 2020, J&J pledged to deliver up to 300 million doses of its vaccine to the U.S., with 100 million upfront and an option for 200 million more. The deal, worth more than $1 billion, will be funded by the Biomedical Advanced Research and Development Authority (BARDA) and the U.S. Defense Department.[24][25] The deal was confirmed on 5 August.[26]
In September 2020, Grand River Aseptic Manufacturing agreed with J&J to support the manufacture of the vaccine, including technology transfer and fill and finish manufacture, at its Grand Rapids, Michigan facility.[27]
In December 2020 J&J and Reig Jofre, a Spanish pharmaceutical company, entered into an agreement to manufacture the vaccine at Reig Jofre's Barcelona facility.[28] If the European Medicines Agency grants approval to the vaccine by March 2021, a European Union regulator said that J&J could start supplying vaccines to EU countries starting on April 2021.[29][30]
In August 2020, J&J signed a contract with the U.S. federal government for US$1 billion, agreeing to deliver 100 million doses of the vaccine to the U.S. following the U.S. Food and Drug Administration (FDA) grant of approval or emergency use authorization (EUA) for the vaccine.[25] Under its agreement with the U.S. government, J&J was targeted to produce 12 million doses by the end of February 2021, more than 60 million doses by the end of April 2021, and more than 100 million doses by the end of June 2021. However, in January 2021, J&J acknowledged manufacturing delays would likely prevent it from meeting its contract of 12 million doses delivered to the U.S. by the end of February.[31]
Regulatory approval process
Beginning on December 1, 2020, clinical trial of the vaccine candidate has been undergoing a "rolling review" process by the European Medicines Agency's Committee for Medicinal Products for Human Use, a step to expedite EMA consideration of an expected conditional Marketing Authorisation Application.[29][32]
On February 4, 2021, J&J applied to the U.S. Food and Drug Administration (FDA) for an EUA, and the FDA announced that its Vaccines and Related Biological Products Advisory Committee would meet on February 26 to consider the application.[7][8][33] J&J previously announced that it planned to ship the vaccine immediately following authorization.[6]
On February 11, 2021, J&J first approval EUA from Saint Vincent and the Grenadines by the Government of Saint Vincent and the Grenadines.[34]
Impact
Given the J&J vaccine is a single dose and has a lower cost, it is expected that the vaccine will play an important role in low and middle-income countries.[35] With lower costs as well as requirements of storage and distribution in comparison to the COVID-19 vaccines by Pfizer and Moderna, the J&J vaccine will be more easily transported, stored, and administered.[36] South African health minister Zweli Mkhize announced on 9 February 2021 to sell or swap its one million doses of AstraZeneca vaccine. Mkhize said South Africa would begin using Ad26.COV2.S the week of 15 February.[37]
References
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