Clinical trials for the vaccine were started in June 2020, with phaseIII involving around 43,000 people.[32] In January 2021, Janssen announced that 28 days after a completed vaccination, the vaccine was 66% effective in a one-dose regimen in preventing symptomatic COVID‑19, with an 85% efficacy in preventing severe COVID‑19[33][34][35] and 100% efficacy in preventing hospitalization or death caused by the disease.[36]
Because cases of thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome have been reported after receipt of the Janssen COVID‑19 vaccine, the US Centers for Disease Control and Prevention (CDC) recommends "preferential use of mRNA COVID‑19 vaccines over the Janssen COVID‑19 vaccine, including both primary and booster doses administered to prevent COVID‑19, for all persons aged 18 years of age and older. The Janssen COVID‑19 vaccine may be considered in some situations, including for persons with a contraindication to receipt of mRNA COVID‑19 vaccines."[41] In February 2022, Johnson & Johnson announced it has temporarily suspended production of the vaccine though they also noted that it will likely resume at some point in the future and that it will honor all pre-existing contracts that oblige Janssen to supply its vaccine by using the millions of already existing vaccine doses in its inventory where requested.[42]
Medical uses
The Janssen COVID‑19 vaccine is used to provide protection against infection by the SARS-CoV-2 virus in order to prevent COVID‑19 in people aged eighteen years and older.[36][1]
A vaccine is generally considered effective if the estimate is ≥50% with a >30% lower limit of the 95% confidence interval.[45] Efficacy is closely related to effectiveness, which is generally expected to slowly decrease over time.[46]
In October 2021, Janssen reported at a meeting of the US Food and Drug Administration Vaccines and Related Biological Products Advisory Committee (VRBPAC) that a single dose produced durable protection against severe disease and hospitalization for at least 6 months in the United States, even when Delta emerged, but also a global decrease in protection against moderate disease attributed to emerging variants outside the US. Janssen also reported that a booster dose given 2 months after the primary dose increased efficacy against symptomatic disease to 75% (95% CI, 55–87%) globally and to 94% (59–100%) in the US and that it also increased efficacy against severe disease to nearly 100% (33–100%) globally.[51][52]
Unpunctured vials may be stored between 9 and 25 °C (48 and 77 °F) for up to twelve hours,[30][53] and the vaccine can remain viable for months in a standard refrigerator.[62][63][64][65][66] It is not shipped[30][67] or stored frozen.[30]
In April 2020, Johnson & Johnson entered a partnership with Catalent to provide large-scale manufacturing of the Johnson & Johnson vaccine at Catalent's Bloomington, Indiana facility.[68] In July 2020, the partnership was expanded to include Catalent's facility in Anagni, Italy.[69]
In December 2020, Johnson & Johnson and Reig Jofre, a Spanish pharmaceutical company, entered into an agreement to manufacture the vaccine at Reig Jofre's Barcelona facility.[71]
In February 2021, Sanofi and Johnson & Johnson struck a deal for Sanofi to provide support and infrastructure at Sanofi's Marcy-l'Étoile, France facility to manufacture approximately twelve million doses of the Johnson & Johnson vaccine per month once authorized.[72]
In March 2021, Merck & Co and Johnson & Johnson struck a deal for Merck to manufacture the Johnson & Johnson vaccine at two facilities in the United States to help expand the manufacturing capacity of the vaccine using provisions of the Defense Production Act.[76] That same month, human error at a plant run by Emergent BioSolutions in Baltimore resulted in the spoilage of up to fifteen million doses of the Johnson & Johnson vaccine. The error, which was caught before the doses left the plant, delayed expected shipments of the Johnson & Johnson vaccine within the United States.[77] As the error had involved combining ingredients of the Johnson & Johnson vaccine with the AstraZeneca vaccine, the Biden administration gave control of the plant to Johnson & Johnson and said the plant should produce only the Johnson & Johnson vaccine to avoid further mix-ups.[78] In July 2021, the FDA authorized Emergent to resume production (but not distribution) of the Janssen vaccine.[79] 400million doses were destroyed.[80][81]
Adverse effects
Review of Vaccine Adverse Events Reporting System (VAERS) safety monitoring data by the US Centers for Disease Control and Prevention (CDC) through 21 April 2021, (by which time 7.98million doses of the Janssen COVID‑19 vaccine had been administered), showed that "97% of reported reactions after vaccine receipt were nonserious, consistent with preauthorization clinical trials data."[82]
The most common side effects of the vaccine in the trials were usually mild or moderate, occurred within two days after vaccination, and got better within 1 or 2 days.[83][1][84]
The most common side effects are pain at the injection site, headache, tiredness, muscle pain, and nausea, affecting more than 1 in 10 people. Coughing, joint pain, fever, chills, redness, and swelling at the injection site occurred in less than 1 in 10 people.[1] Sneezing, tremor, throat pain, rash, sweating, muscle weakness, pain in the arms and legs, backache, weakness, and feeling generally unwell occurred in less than 1 in 100 people.[1] Rare side effects (that occurred in less than 1 in 1,000 people) are hypersensitivity (allergy) and itchy rash.[1]
An increased risk of the rare and potentially fatal thrombosis with thrombocytopenia syndrome (TTS) has been associated with mainly younger female recipients of the vaccine.[30][85] This syndrome, marked by formation of blood clots in the blood vessels in combination with low levels of blood platelets 4–28 days after the vaccines administration, occurred at a rate of about 7 per 1 million vaccinated women aged 18–49 years old and it occurs more rarely in other populations (i.e., women 50 years and older and men of all ages).[86]
Allergic reactions, including anaphylaxis, can occur in rare cases within a few minutes to one hour after receiving a dose.[1][87]
In May 2021, with 7.98 million doses administered, the CDC reported four cases of anaphylaxis after vaccination (none of which resulted in death) and 28 cases of cerebral venous sinus thrombosis (of which three resulted in death).[82]
In July 2021, the US fact sheet for the vaccine was updated to indicate that there may be an increased risk of Guillain-Barré syndrome during the 42 days following vaccination.[30][88][89] The European Medicines Agency (EMA) listed Guillain-Barré syndrome (GBS) as a very rare side effect of COVID‑19 Vaccine Janssen and added a warning in the product information.[90]
In August 2021, the Pharmacovigilance Risk Assessment Committee (PRAC) recommended updating the product information to the European Medicines Agency (EMA) that "cases of dizziness and tinnitus (ringing or other noises in one or both ears) are linked to the administration of COVID‑19 vaccine Janssen."[91] Tinnitus was later labeled as "very rare" in a final safety study by the manufacturer.[92]
In December 2021, the CDC accepted the recommendation from a panel of experts for a preference of using the Pfizer-BioNech and Moderna vaccines over the Janssen vaccine due to rare but serious blood clotting events.[93] In May 2022, the FDA limited the use of the Janssen vaccine to those over eighteen unable to access other vaccines or who are otherwise "medically ineligible" for other vaccine options.[94][95]
In June 2020, Johnson & Johnson and the National Institute of Allergy and Infectious Diseases (NIAID) confirmed that they planned to start clinical trials of the Ad26.COV2.S vaccine in September 2020, with the possibility of phaseI–IIa human clinical trials starting at an accelerated pace in the second half of July.[107][108][109]
A phase I–IIa clinical trial started with the recruitment of the first subject in July 2020 and enrolled study participants in Belgium and the US.[110] Interim results from the phaseI–IIa trial established the safety, reactogenicity, and immunogenicity of Ad26.COV2.S. With one dose, after 29 days, the vaccine ensured ninety percent of participants had enough antibodies required to neutralize the virus. After 57 days, that number reached one hundred percent. 1x1011 viral particles (high dose) provided an increase in the neutralizing-antibody titers compared to 5×1010 (low dose). After the second dose 56 days after the first dose among participants between the ages of 18 and 55 years, the incidence of grade 3 solicited systemic adverse events was much lower than that after the first immunization in both the low-dose and high-dose groups, a finding that contrasts with observations with respect to messenger RNA–based vaccines, for which the second dose has been associated with increased reactogenicity.[111][112] A substudy with 20 participants found that humoral and cell-mediated immune responses, including cytotoxic T cells, lasted for at least 8 months.[113][unreliable medical source?]
Phase III
A phase III clinical trial called ENSEMBLE started enrollment in September 2020 and completed enrollment in December 2020.[28] It was designed as a randomized, double-blind, placebo-controlled clinical trial intended to evaluate the safety and efficacy of a single-dose vaccine versus placebo in adults aged 18 years of age and older. Study participants received a single intramuscular injection of Ad26.COV2.S at a dose level of 5×1010 virus particles on day one.[114] The trial was paused in October 2020, because a volunteer became ill,[115][106] but the company said it found no evidence that the vaccine had caused the illness and announced in October 2020 that it would resume the trial.[116][117] In January 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 five deaths in the placebo group were related to COVID‑19.[118] During the trial, no anaphylaxis was observed in participants.[118]
A second phase III clinical trial called ENSEMBLE2 started enrollment in November 2020. ENSEMBLE2 differed from ENSEMBLE in that its study participants received two intramuscular (IM) injections of Ad26.COV2.S, one on day1 and the next on day 57.[119] Early results indicated 85% efficacy against severe/critical disease.[113][47] Plasma from 8 participants showed greater neutralization activity against the Delta variant than against Beta.[113]
Authorizations
Graphs are unavailable due to technical issues. Updates on reimplementing the Graph extension, which will be known as the Chart extension, can be found on Phabricator and on MediaWiki.org.
Beginning in December 2020, clinical trial of the vaccine candidate has been undergoing a "rolling review" process by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA), a step to expedite EMA consideration of an expected conditional marketing authorization.[120][121] In February 2021, Janssen applied to the EMA for conditional marketing authorization of the vaccine.[5][122] The European Commission approved the COVID‑19 Vaccine Janssen in March 2021.[1][40] In Finland, the Janssen vaccine is only offered for those aged 65 and over.[123][124]
United States
In February 2021, Janssen Biotech applied to the US Food and Drug Administration (FDA) for an emergency use authorization (EUA), and the FDA announced that its Vaccines and Related Biological Products Advisory Committee (VRBPAC) would meet in February to consider the application.[62][67][125][126] In February, ahead of the VRBPAC meeting, briefing documents from Janssen and the FDA were issued; the FDA document recommends granting the EUA, concluding that the results of the clinical trials and the safety data are consistent with FDA EUA guidance for COVID‑19 vaccines.[53][127][128][129] At the 26 February meeting, VRBPAC voted unanimously (22–0) to recommend that an EUA for the vaccine be issued.[130] The FDA granted the EUA for the vaccine the following day.[32][37][131] In February, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommended the use of the vaccine for those aged 18 and older.[132][38]
In April 2021, the CDC and the FDA issued a joint statement recommending that use of the Janssen vaccine be suspended, due to reports of six cases of cerebral venous sinus thrombosis—a "rare and severe" blood clot—in combination with low levels of blood platelets (thrombocytopenia), in six women between the ages of 18 and 48 who had received the vaccine.[133] The symptoms occurred 6–13 days after they had received the vaccination, and it was reported that one woman had died and a second woman had been hospitalized in critical condition.[134][135][136]
In April, the FDA and the CDC determined that the recommended pause regarding the use of the Janssen COVID‑19 Vaccine in the US should be lifted and use of the vaccine should resume.[137][138] The EUA and the fact sheets were updated to reflect the risks of thrombosis-thrombocytopenia syndrome (TTS).[137]
The FDA granted an emergency use authorization and the CDC issued a standing order for the use of the vaccine.[36][32][37][83][87]
In June 2023, the FDA revoked the emergency use authorization for the Janssen COVID-19 vaccine at the request of its manufacturer.[20][21]
In December 2020, Johnson & Johnson entered into an agreement in principle with the GAVI vaccine alliance to support the COVAX Facility. In February 2021, Johnson & Johnson submitted its formal request and data package to the World Health Organization for an Emergency Use Listing (EUL); an EUL is a requirement for participation in COVAX. Johnson & Johnson anticipated providing up to five hundred million doses through 2022 for COVAX.[63][140][141] The World Health Organization issued an EUL for the Janssen COVID‑19 vaccine Ad26.COV2.S vaccine in March 2021.[142][143]
In February 2021, the vaccine received emergency authorization in South Africa.[144][145][146] In April 2021, South Africa suspended its rollout of the vaccine.[147] The program resumed in April 2021.
In February 2021, Bahrain authorized the vaccine for emergency use.[148][149]
In February 2021, the South Korean Ministry of Food and Drug Safety began a review of Johnson & Johnson's application for approval of its vaccine.[150]
In late November 2020, Johnson & Johnson submitted a rolling review application to Health Canada for approval of its vaccine.[151]
In March 2021, the vaccine received emergency authorization in Colombia.[152]
In March 2021, the vaccine was authorized under interim order in Canada.[153]
In April 2021, the Australian government stated that it would not be purchasing the Janssen vaccine, as it "does not intend to purchase any further adenovirus vaccines at this time".[154][155] The Therapeutic Goods Administration granted provisional approval for use of the Janssen vaccine in Australia in June 2021.[6][7]
In April 2021, the vaccine received emergency use authorization in the Philippines.[156][157]
In May 2021, the vaccine received conditional marketing authorization in the United Kingdom.[17][18][19][158][105]
In June 2021, the vaccine received emergency use authorization in Chile. The vaccine will be provided via COVAX.[159]
In June 2021, Malaysia's National Pharmaceutical Regulatory Agency (NPRA) issued conditional registration for emergency use of the vaccine.[160]
In June 2021, COVID‑19 Janssen Ad26.COV2.S was granted provisional approval in Australia.[6][7]
In July 2021, the vaccine received provisional approval for use for people aged 18 and above in New Zealand.[161][162]
In August 2021, Health and Family Welfare Minister of India announced that Johnson and Johnson single-dose vaccine was approved for emergency use in India through a supply agreement with homegrown vaccine maker Biological E. Limited.[163]
In November 2021, the vaccine's authorization under interim order in Canada was transitioned to approval for use under the country's Food and Drug Regulations.[11][12][13]
In August 2023, the COVID-19 Vaccine Janssen was removed from the Australian Register of Therapeutic Goods at the request of Janssen-Cilag Pty Ltd.[165] The vaccine was never supplied in Australia.[165]
About 19.4million doses of the Janssen COVID-19 vaccine were administered in the EU/EEA from authorization to 26 June 2022.[169]
Economics
Given the Janssen vaccine is a single dose and has a lower cost, it was expected to play an important role in low and middle-income countries.[170] Since it is a single dose vaccine, it has been a popular vaccine to distribute to the homeless,[171][172][173][174] the incarcerated,[175][176][174] and refugee populations.[177][176][174][178] This is due to the fact that it is difficult for these aforementioned demographics to be contacted for vaccines that require a second dose. With lower costs and lower requirements of storage and distribution in comparison to the COVID‑19 vaccines by Pfizer and Moderna, the Janssen vaccine is more easily transported, stored, and administered.[179] South African health minister Zweli Mkhize announced on 9February 2021 that the country would sell or swap its one million doses of AstraZeneca vaccine.[180] Once it did so, South Africa began vaccination using the Janssen vaccine in February 2021,[146] marking the vaccine's first use outside of a clinical trial.[181]
In August 2020, Johnson & Johnson signed a contract with the US federal government for $1billion, agreeing to deliver one hundred million doses of the vaccine to the US following the Food and Drug Administration (FDA) grant of approval or emergency use authorization (EUA) for the vaccine.[183] Under its agreement with the US government, Johnson & Johnson was targeted to produce twelve million doses by the end of February 2021, more than sixty million doses by the end of April 2021, and more than one hundred million doses by the end of June 2021. However, in January 2021, Johnson & Johnson acknowledged manufacturing delays would likely prevent it from meeting its contract of twelve million doses delivered to the US by the end of February.[185] In February 2021, through congressional testimony by a company executive, Johnson & Johnson indicated that the company could deliver twenty million doses to the US government by the end of March and one hundred million doses in the first half of 2021.[186]
In February 2021, Johnson & Johnson announced that it planned to ship the vaccine immediately following authorization.[118]
In March 2021, the Canadian government placed an order with Johnson & Johnson for ten million doses, with an option to purchase up to twenty-eight million more; on 5March, the vaccine became the fourth to receive Health Canada approval.[187]
Shipments of the vaccine were scheduled to start in the second half of April 2021, with a commitment to deliver at least two hundred million doses to the EU in 2021.[188]
The European distribution of the vaccine was slightly delayed until the EMA decided that rare cases of vaccine-induced blood clots did not outweigh the benefits of helping to fight the COVID‑19 pandemic.[189]
Controversies
The United States Conference of Catholic Bishops expressed concern about the vaccine because the cell line Per.C6, which is used in development and production, was originally derived from the retinal tissue of an 18-week-old fetus electively aborted in 1985.[190][191][192][193] Although the use of fetal tissue in vaccine development has become common since the 1930s, especially with cell-based vaccines, there are currently alternatives that do not carry the same potential ethical concerns as the Janssen vaccine.[194][195] Some bioethicists dismiss that ethical concerns to using cells derived from ethically compromised sources should be addressed or alternatives sought.[196] Others advance the view that the cells used for COVID‑19 vaccines are thousands of generations removed from their source material and do not contain any fetal tissue.[190][191]
In December 2020, the Vatican published a note approved by Pope Francis, stating that "...all [COVID-19] vaccinations recognized as clinically safe and effective can be used in good conscience..."[190][197] However, the key objection to using these vaccines still remains.[198][197][199]
In September 2021, after criticism that doses of its single-shot COVID‑19 vaccine produced in Aspen Pharmacare's facility in South Africa were being exported to Europe, millions of doses that had been shipped to Europe and stored in warehouses will be returned to Africa, and newly manufactured doses will be shipped to African countries.[200]
^21 September 2020 to 22 January 2021 in the United States, South Africa and Brazil.[30][47]
^Wuhan-H1 variant D614G.[48] Corresponds to 96% of the strains the United States during the study.
^Effectiveness from a study with 97,787 participants from 27 February to 22 July 22, 2021 in the United States.[49]
^Generally includes mild symptoms such as olfactory or taste disorders and moderate symptoms such as pneumonia.
^ abGenerally understood as requiring some form of hospitalization (from supplemental oxygen therapy to ICU admission). The same statistical variable includes cases of death.
^A confidence interval was not provided, so it is not possible to know the accuracy of this measurement.
^Effectiveness against hospitalization from a preliminary study with 477,000 healthcare workers.[50]
^ abcd"COVID-19 Vaccine Janssen". Therapeutic Goods Administration (TGA). 25 June 2021. Archived from the original on 28 August 2021. Retrieved 28 August 2021.
^ abc"COVID-19 vaccine: Janssen". Therapeutic Goods Administration (TGA). 27 August 2021. Archived from the original on 28 August 2021. Retrieved 28 August 2021.
^ abc"FDA Roundup: June 2, 2023". U.S. Food and Drug Administration (Press release). 2 June 2023. Archived from the original on 3 June 2023. Retrieved 2 June 2023.
^ abClinical trial number NCT04505722 for "A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Mediated COVID-19 in Adult Participants (ENSEMBLE)" at ClinicalTrials.gov
^ abc"FDA Letter of Authorization"(PDF). U.S. Food and Drug Administration (FDA). 27 February 2021. Archived from the original on 10 March 2021. Retrieved 28 February 2021. ...letter is in response to a request from Janssen Biotech, Inc. that the Food and Drug Administration (FDA) issue an Emergency Use Authorization (EUA)...
^Krause P, Fleming TR, Longini I, Henao-Restrepo AM, Peto R (September 2020). "COVID-19 vaccine trials should seek worthwhile efficacy". Lancet. 396 (10253): 741–743. doi:10.1016/S0140-6736(20)31821-3. PMC7832749. PMID32861315. WHO recommends that successful vaccines should show an estimated risk reduction of at least one-half, with sufficient precision to conclude that the true vaccine efficacy is greater than 30%. This means that the 95% CI for the trial result should exclude efficacy less than 30%. US Food and Drug Administration guidance includes this lower limit of 30% as a criterion for vaccine licensure.
^Zhukova A, Blassel L, Lemoine F, Morel M, Voznica J, Gascuel O (November 2020). "Origin, evolution and global spread of SARS-CoV-2". Comptes Rendus Biologies. 344 (1). French Academy of Sciences: 57–75. doi:10.5802/crbiol.29. PMID33274614. S2CID227283362. Sequences containing the G614 version, together with two mutations at the RNA level, constitute the G clade of GISAID, named B1 by the PANGOLIN system.
^"Janssen COVID-19 Vaccine (Ad26.COV2.S)". 14 October 2021. Archived from the original on 24 August 2021. Retrieved 23 August 2021. 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. 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
^"Drug Levels and Effects". COVID-19 vaccines. Bethesda (MD): National Library of Medicine (US). 2006. PMID33355732. Archived from the original on 30 June 2021. Retrieved 15 October 2021.
^"Janssen Letter Granting EUA Amendment"(PDF). U.S. Food and Drug Administration (FDA). 12 July 2021. Archived from the original on 12 July 2021. Retrieved 13 July 2021. Reports of adverse events following use of the Janssen COVID-19 Vaccine under emergency use authorization suggest an increased risk of Guillain-Barré syndrome during the 42 days following vaccination.
^Clinical trial number NCT04614948 for "A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults (ENSEMBLE 2)" at ClinicalTrials.gov
^"COVID-19 vaccines safety update"(PDF). 3 August 2022. Archived(PDF) from the original on 3 August 2022. Retrieved 3 August 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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Third most populous city of Scotland This article is about the city in Scotland. For other uses, see Aberdeen (disambiguation). City and council area in ScotlandAberdeen Aiberdeen (Scots)Obar Dheathain (Scottish Gaelic)City and council areaAberdeen HarbourAberdeen Town HouseMarischal CollegeHis Majesty's TheatreAberdeen Arts Centre Coat of armsFlag of Aberdeen City Council[1]Nicknames: Granite City, The Silver City by Sea, Oil Capital of EuropeAberdeenAberdeen locality ...
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Untuk musim terkini, lihat Asia's Next Top Model, Siklus 6. Asia's Next Top ModelPembuatTyra BanksJuriSekarang:Cindy BishopYu TsaiDahulu:Nadya Hutagalung[1]Georgina WilsonDaniel BoeyTodd Anthony TylerAdam WilliamsMike RosenthalJoey Mead KingAlex PerryKelly TandionoCara McIlroyNegara asal Singapura Malaysia ThailandJmlh. musim6Jmlh. episode75ProduksiDurasi43 - 45 menitRumah produksiIce-TV (siklus 1) Fox Networks Group (siklus 2-7) activeTV (siklus 2) Beach House Pict...
Logo The Takamatsu-Kotohira Electric Railroad Co., Ltd. (高松琴平電気鉄道株式会社, Takamatsu-Kotohira Denki Tetsudō Kabushiki-gaisha) (or Kotoden) is a transportation company in Kagawa Prefecture, which is on the island of Shikoku, Japan. With headquarters in Takamatsu, the company operates three passenger railway lines, as well as bus subsidiaries. It was established on the 1st of November 1943. In 2021, it reported sales of ¥2,881,000,000 with a capitalization of ¥250,000,000...