Vaccines to protect against Covid-19, the new coronavirus infection
Covid-19, the disease caused by the SARS-CoV-2 coronavirus, affects people all over the world. However, companies and research institutes are developing vaccines. Two vaccines have now been approved in the EU.
At least 246 vaccine projects have started against Covid-19 since January 2020: The World Health Organization (WHO) currently counts 235 (listing as of Jan. 12, 2021). In addition, there are at least eleven other projects that it does not yet list. These are projects of the following companies and institutes:
- the start-up Prime Vector Technologies (PVT) (Tübingen)
- the start-up baseclick (Neuried near Munich) - RNA vaccine
- the start-up Belyntic (Berlin) in cooperation with a university - peptide vaccine
- the Viennese company Viravaxx and the University of Vienna
- the Viennese company Cebina with the University of Pécs (Hungary)
- the US company Sorrento Therapeutics
- the US company Elixirgen Therapeutics (RNA vaccine EXG-5003)
- the South Korean company SK Bioscience
- Tel Aviv University, Israel (RNA vaccine)
- the companies Dyadic and Epygen (USA and India) (subunit vaccine)
Development and production of Covid-19 vaccines in Germany
Internationally, Germany is one of the countries with a particularly large number of Covid-19 vaccine projects, as shown in the map above. A static map of these locations can also be downloaded.
In detail, the following companies and research institutions are working on vaccines:
- the companies BioNTech / Pfizer (Mainz, Idar-Oberstein, Marburg), two projects
- the company CureVac (Tübingen)
- the company Leukocare (Planegg) with ReiThera (Italy) and Univercells (Belgium) - vector virus vaccine that has been tested in Italy with volunteers since 24.08.
- the start-up Prime Vector Technologies (PVT) (Tübingen) - vector virus vaccine
- the company ARTES Biotechnology (Langenfeld, Rhineland) - Vaccine with virus-like particles (VLP)
- the start-up Belyntic (Berlin) in cooperation with a university - peptide vaccine
- the German Centre for Infection Research (Braunschweig) / Univ. Munich / Univ. Marburg / UKE Hamburg / IDT Biologika (Dessau-Roßlau) - MVA-based vaccine that has been tested with volunteers since October
- the German Centre for Infection Research / CanVirex (Braunschweig / Basel, Switzerland) - measles vaccine based on the measles virus
- University Hospital Tübingen - Peptide vaccine
- the start-up baseclick (Neuried near Munich) - RNA-based vaccine
- the ContiVir research project of the Max Planck Institute for Dynamics of Complex Technical Systems in Magdeburg - VLP vaccine
In addition, the following companies and research institutes play a supporting role in vaccine development or production:
- Rentschler Biopharma (Laupheim): takes over a production step for the vaccine from BioNTech/Pfizer
- Dermapharm (Brehna): is involved in the production of the vaccine by BioNTech/Pfizer
- Siegfried (Hameln): participates in filling and packaging of the vaccine from BioNTech/Pfizer
- Allergopharma (Reinbek) will participate in the production of the BioNTech/Pfizer vaccine in the future
- Vibalogics (Cuxhaven): produces component for Janssen's vaccine
- CEVEC Pharmaceuticals (Cologne): produces components for unnamed manufacturer
- Richter-Helm BioLogics (Hamburg): produces DNA material for Inovio (USA)
- WuXi (Wuppertal) will participate in the production of AstraZeneca's vaccine from the end of 2021 onwards
- the company Daiichi Sankyo Europe (Pfaffenhofen near Munich) and the University of Munich (Department of Pharmacy) contribute to the vaccine project of Daiichi-Sankyo (Japan) and the University of Tokyo
- Sanofi (Frankfurt a.M.): will fill vaccine from the cooperation between Sanofi and GSK
- R-Pharm Germany (Illertissen), subsidiary of the Russian company R-Pharm: will produce vaccine from AstraZeneca under licence
- Merck (Darmstadt): supports production of the vaccine by Oxford University/AstraZeneca and Baylor College (University of Texas, USA)
- Recipharm (Wasserburg): develops production processes for another company
- University of Giessen: participates in the OpenCorona consortium (lead: Karolinska Institute, Sweden), which is developing a DNA-based vaccine
- Tropical Institute of the University of Tübingen: will test inactivated vaccine of the Danish-Dutch-German PREVENT-nCoV consortium
In addition, plans are being pursued at the University Hospital of Tübingento develop a vector virus vaccine (using sednaviruses) against covid-19 that can be administered as a nasal spray. However, the project leaders expect it to take at least four years to develop the vaccine before it can be approved, and only if funding can be found for the project.
Status of vaccine development
Each project for a Covid 19 vaccine comprises seven parts, some of which overlap. They are shown in the graphic below:
The seven stages of vaccine development
Vaccines against Covid-19 - The worldwide development status in figures:
Until a few years ago, it would have taken 15 to 20 years from virus analysis to vaccine approval. New technologies and prior experience with vaccine projects against related viruses (see below) make a tremendous acceleration possible. Two vaccines have already been approved, and many others are currently being tested with volunteers, some of which are already in the final phase III trials. This is shown in the following table (for explanations of the vaccine types, see below):
|Company / Research institute||Vaccine||Vaccine type||Testing with volunteers||Production||Financial support||Sources|
|BioNTech / Pfizer // BioNTech / Fosun Pharma||BNT162b2||mRNA-based vaccine||Approval in the EU on 21/12/2020. Emergency approvals in UK (02/12/2020), in the US (11/12/2020). Further approvals in other countries. Phase III trial since 27.07.2020 in the USA, Brazil, Argentina, Germany, Turkey and South Africa; result: 95% efficacy in preventing covid 19 disease, also in seniors. In addition, phase I trial with Fosun Pharma in China. EU approval was preceded by "rolling review".||in Mainz / Idar-Oberstein / Marburg / Puurs (Belgium) / Kalamazoo (Michigan, USA) / Andover (Massachusetts, USA) / Chesterfield (Missouri, USA), also manufacturing steps at Rentschler Biopharma (Germany), Polymun (Austria), Dermapharm (Germany), Acuitas Therapeutics (Canada); filling at Siegfried (Hameln, Germany); sterile manufacturing services at Baxter BioPharma Solutions in Halle (Westphalia, Germany).||Horizon 2020 InnovFin, European Fund for Strategic Investments, BMBF||The Wall Street Journal Entry EU Clinical Trials Register, Pr.mitt. Pfizer, Crain's Detroit Business, Pr.mitt. BioNTech, Mitteldeutsche Zeitung, Wiener Zeitung, Pr. mitt. BioNTech/Pfizer, Pr .mitt. BioNTech, DGAP, Pr. mitt. Rentschler Biopharma, Pr .mitt. BioNTech/Pfizer; Pr. mitt. BioNTech/Pfizer, Pr.mitt. Pfizer/BioNTech, tagesschau.de, Pr.mitt. BioNTech/Pfizer; Pr.mitt. BioNTech/Pfizer, EMA, Pr .mitt. BioNTech, Pr.mitt. BioNTech|
|Moderna (USA)||mRNA-1273||mRNA-based vaccine||Approvalin the EU on 06.01.2021. Approval also in the USA and other countries. Phase III study showed efficacy of 94.1% in preventing covid-19 disease and 100% in preventing severe covid-19 disease. The companies had already submitted parts of the marketing authorization application to EMA in advance for "rolling review".||Manufactured at own facility in the US; by Lonza (in Portsmouth, New Hampshire [US], and in future in Visp [Switzerland]); formulation at Recipharm (France); filling at Recipharm (France), Catalent (US) and Rovi (Spain); lipid supply from Corden Pharma (facilities in Switzerland, France, US); distribution partners in Japan: Takeda||CEPI, BARDA||ABC News, Bloomberg, Forbes, Reuters, Pr.mitt. Moderna, Pr. mitt. Moderna, Fierce Pharma, FoxSanAntonio, Der Aktionär, Pr. mitt. Moderna, Pr.mitt . Moderna, BBC News, Pr.mitt . EMA, Pr.mitt. Moderna, tagesschau.de, EMA, Reuters|
|AstraZeneca Life Science / Oxford University (UK)||ChAdOx1 nCoV-19 (AZD1222)||Vector virus vaccine (based on an adenovirus that cannot replicate in human cells)||In the approval process in the EU since 12/01/2021 with the prospect of evaluation by the end of January, as part of the marketing authorization application has already been previously worked through in the "rolling review". Approved in UK since 30.12. for "emergency supply". Licensed version "Covishield" of the Serum Institute of India approved in India since 02.01. for "emergency use". Previously studies in Brazil (since end of June), USA (since beginning of September) and UK. Interim result from phase III with healthy participants up to 55 years of age and dosage "first half, then full dose": 90 % efficacy; interim result from phase III with participants of any age, including those with previous illnesses, and dosage "twice full dose": 62 % efficacy.||Production in full or in individual manufacturing steps by AstraZeneca, Halix (Netherlands), Pall Life Science, Cobra Biologics (USA, UK, Sweden), Oxford Biomedica (UK), Novasep (Belgium), Albany Molecular (USA), Reig Jofre (Spain); in future also at the UK Vaccines Manufacturing and Innovations Centre (VMIC). Production under license also by Serum Institute of India (as "Covishield"), SK Bioscience (South Korea), R-Pharm (Russia + Germany), CSL (Australia), Siam Bioscience Group (Thailand), mAbxience (INSUD Group, Argentina).||CEPI, UK's Natl. Institute for Health Research, UK Research & Innovation, BARDA (USA)||The Guardian Online, Merck report, The Lancet, The Telegraph, inews, LiveScience, BBC, BBC, clinicaltrials.gov, Statnews, Fiercepharma Reuters, Oxford University, Reuters,Fierce Pharma, Pr.mitt. CSL, The Phuket News, NTV News, Pr.mitt. AstraZeneca, NTV, BBC, DAZ Online, Pr. mitt. Reig Jofre, Reuters, Pr.mitt . Novasep, Pr.mitt. EMA|
|Sinopharm / Wuhan Institute of Biological Products / Wuhan Institute of Virology of the Chinese Academy of Sciences||inactivated Novel Coronavirus Pneumonia (COVID-19) vaccine (Vero cells)||Vaccine with inactivated virus||in phase III in China, the United Arab Emirates and Bahrain and Peru; in an interim evaluation, the vaccine has an efficacy of 79% according to the publication of 29.12.2020; it was approved in China on 30.12.||tbd||n / a||Clinicaltrialsarena, ChiCTR, CGTN, Reuters, CNN, South China Morning Post|
|Sinovac Biotech||CoronaVac||Vaccine with inactivated virus||in Phase III in Brazil and other countries since 21.07.2020 (partnership with Instituto Butantan); interim results from studies indicate reliability between 50% and 91%; Hungary has signed supply agreement with Sinovac, according to media reports||tbd||n / a||Pr.mitt. Sinovac, Clinicaltrials.gov, CGTN, Fierce Pharma, clinicaltrials.gov, Reuters, Bangkok Post, BBC, CGTN|
|Beijing Institute of Biological Products / Sinopharm||tbd||Dead vaccine (inactivated viruses)||in phase III||in own facility||n / a||WHO, Reuters, Asharq Al-Awsat|
|Natl. Gamaleya Research Centre for Epidemiology and Microbiology (Russia), Ministry of Health of Russia||Gam-COVID-Vac = Sputnik V||Vector virus vaccine (adenovirus)||in Phase III trial since 31.08. in Russia, since 28.09. also in Belarus; already approved in Russia after Phase II||by Binnopharm (Russia)||n / a||Sputnik Germany, TASS, AA|
|CanSino Biologics (China) / Beijing Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China||Ad5-nCoV||Vector virus vaccine (adenovirus type 5)||in Phase III trials in Pakistan and Russia; trial planned in Saudi Arabia; planned trial in Canada cancelled||with the National Research Council of Canada (NRC) (cell line HEK293) in Montreal (Canada)||Government of Canada (for production in Canada)||Nature Reviews Drug Discovery, Clinicaltrials.gov registry entryPr.mitt. Natl. Research Councel Canada, Hindustan Times, Reuters, TrialSiteNews|
|Janssen (Johnson&Johnson)||Ad26.COV2-S||Vector virus vaccine||in Phase III trial since Sept. 23; parts of marketing application in "rolling submission" already submitted to EMA in advance. Phase III trial ongoing in USA, Brazil, Chile, Colombia, Mexico, Peru, South Africa, Ukraine and Philippines. Meanwhile, the Phase II trial is ongoing in the Netherlands, Germany (UKE, Charité Berlin, Uniklinik Rostock) and Spain.||in own facilities in Bümpliz (Switzerland) and Leiden (Netherlands) / by Catalent Biologics (USA) / supplied by Emergent BioSolutions (USA) / supplied for vaccine for clinical trials by Vibalogics (Cuxhaven) / probably also manufactured by Aspen Pharmacare (South Africa)||US Biomedical Advanced Research and Development Authority (BARDA)||News Johnson&Johnson, Article Johnson&Johnson, Langenthaler Tagblatt, Biopharma Reporter, Biopharma Reporter, FiercePharma, Pr.mitt. Vibalogics Pr.mitt. Janssen, Biopharma Reporter, S&P Global Market Intelligence, MOPO, clinicaltrials.gov, Pr.mitt. Janssen, CNN, Reuters, Pr.mitt. EMA|
|Novavax||NVX-CoV2373||Dead vaccine with genetically engineered viral antigen (nanoparticle technology) and saponin-based adjuvant||in Phase III trial in UK since end of September, in USA since December; also planned for Mexico||by Emergent BioSolutions (USA) and in future by subsidiary Praha Vaccines (Czech Republic). Adjuvant supplied by AGC Biologics (USA and Denmark) and PolyPeptide Group (USA and Sweden) and antigen by Fujifilm Diosynth (UK) and Biofabri (Spain), SK Bioscience (South Korea) and Takeda Pharmaceuticals (Japan). Filling also by Par Sterlie Products (USA). Under license also antigen production and filling by Serum Institute of India (India).||CEPI, US Government (Operation Warp Speed)||Pr.mitt. Novavax, clinicaltrials.gov, Pr.mitt. Novavax, Novavax quarterly report, ABC News, Pr.mitt. Novavax, Handelsblatt; Pr. mitt. Novavax, pr.mitt . Novavax, NDTV, Reuters|
|Bharat Biotech / Indian Council of Medical Research / Natl. Institute of Virology (India)||Covaxin (BBV152)||Vector virus vaccine||In phase III in India since Nov. 12, 2020 (target: 26,000 participants); approved for "emergent use" in India since Jan. 02, 2021, although efficacy results have not yet been published||n / a||n / a||Pr.mitt. Bharat Biotech, expresspharma.in, Zeenews, Reuters, NDTV, Hindustan Times|
|Anhui Zhifei Longcom Biopharmaceutical / Institute of Microbiology, Chinese Academy of Sciences||n / a||Subunit vaccine (antigen and adjuvant)||in phase III since 30.11.2020||n / a||n / a||CNBCTV18, CHICTR|
|Research Institute for Biological Safety Problems / Natl. Scientific Center for Phthisiopulmonology of the Republic of Kazakhstan (Kazakhstan)||QazCovid-in||Vaccine with inactivated SARS-CoV2||in phase III trial in Kazakhstan since 25.12.2020||n / a||n / a||clinicaltrials.gov, clinicaltrials.gov|
|Inovio (USA)||INO-4800||DNA-based vaccine administered by electroporation||since 16.11.2020 in Phase II part of a Phase II/III trial in the USA||by Richter-Helm BioLogics (Germany), VGXI (USA), Ology Bioservices (USA), Advaccine (China, for China); Advaccine also participates in studies and may later commercialize the vaccine in China||CEPI, US Department of Defense||Inovio, Inovio, Clinicaltrials.gov registry entry, Pr.mitt. Inovio, Pr. mitt. Inovio, Pr.mitt. Inovio/Advaccine|
|Medicago (Canada) / GSK||CoVLP||Dead vaccine with virus-like particles from antigens produced in plants and adjuvant from GSK||since 19.11.2020 in phase II part of a phase II/III trial in Canada||n / a||n / a||Medicago, Financial News, Pr.mitt. Medicago/GSK|
|Vector Virology Institute (Russia)||EpiVacCorona||inactivated vaccine with peptide antigens||Approved in Russia on Oct. 14, 2020, following phase II trial||n / a||n / a||Clinicaltrialsarena, clinicaltrials.gov, TASS|
|CureVac||CVnCoV||mRNA-based vaccine||in Phase IIb/III study in Europe and Latin America since 14.12.2020||in own facility in Tübingen; mRNA production also by Wacker in Amsterdam; formulation by Polymun (Austria); filling and packaging by Fareva (France); Tesla will build mobile production facilities||CEPI, EU Commission, Federal Government (KfW Bank)||Pr.mitt. CureVac, Grenzecho, Pr.mitt. CureVac, Pr. mitt. CureVac, dpa, Pr. mitt. CureVac, Fierce Pharma, Mitteldeutsche Zeitung; Pr.mitt. Curevac, FAZ, Pr.mitt. Curevac, Pr. mitt. CureVac and Fareva, Pr.mitt. CureVac, Polymun|
|AnGes (Japan) / Osaka University / Takara Bio||AG0302-COVID19||DNA-based vaccine with adjuvant||in Phase II/III in Japan since November 23rd||by Takara Bio Inc. (Japan)||n / a||Japan Times, Japan Times, clinicaltrials.gov, clinicaltrials.gov|
|Shenzhen Kangtai Biological Products / Beijing Minhai Biotechnology||n / a||inactivated SARS-CoV-2 (produced with Vero cells)||since 27.10. in Phase II in China||n / a||n / a||CHICTR|
|Beijing Wantai Biological Pharmacy / Xiamen University||DelNS1-2019-nCoV-RBD-OPT1||Vector virus vaccine based on influenza virus (intranal spray)||in phase II trial in China since approx. 17.11.2020||n / a||n / a||CHICTR|
|West China Hospital, Sichuan University||recombinant SARS-CoV-2 vaccine (Sf9 cell)||Inactivated vaccine with genetically engineered protein antigen and adjuvant||Phase II trial in China since 17.11.2020||n / a||n / a||Chinese Clinical Trial Registry, clinicaltrials.gov|
|Israel Institute for Biological Research (IIBR) of the Israeli Ministry of Defense||Brilife||Vector virus vaccine based on the virus VSV||in phase II part(since approx. 16.12.2020) of a phase I/II study in Israel||n / a||n / a||The Jerusalem Post, Haaretz, MENAFM, The Jerusalem Post|
|AstraZeneca / R-Pharm||AZD1222||Combination of two vector virus vaccines: ChAdOx1 (from AstraZeneca) and rAd26-S (adenovirus type 26 component of the Gam-COVID-Vac vaccine). The vaccines are injected 28 days apart.||In phase II (since 29/12/2020) in Azerbaijan.||n / a||n / a||clinicaltrials.gov|
|Zydus Cadila Healthcare (India)||ZyCoV-D||DNA-based vaccine (plasmid)||In phase I/II since 07/14/2020, in Singapore; phase III trial approved.||n / a||n / a||CTRI, News18, Pr.mitt. Zydus Cadila|
|Arcturus Therapeutics (USA) / DukeNUS Medical School (Singapore)||COVID-19 RIGID (ARCT-021)||mRNA-based vaccine (self-replicating mRNA)||Phase I/II trial in Singapore since 04.08.||by Catalent (USA) and Recipharm (headquarters in Sweden); formulation by Polymun (Austria)||n / a||PM Arcturus Therapeutics, quarterly report Arcturus Therapeutics, Pr.mitt. DukeNUS, clinicaltrials.gov, pr.mitt. Recipharm, Polymun|
|Instituto Finlay de Vacunas (Cuba)||FINLAY-FR-1 anti SARS-CoV-2||inactivated vaccine with protein antigen and adjuvant||Phase I/II study in Cuba since 24.08.2020||n / a||n / a||Registro Público Cubano des Ensayos Clínicos|
|Sanofi / GSK||n / a||Inactivated vaccine with antigen and adjuvant produced by genetic engineering (with baculoviruses)||in phase I/II trial in the USA since 03.09.2020; start of a phase IIb trial planned from February 2021, after revision of the composition of the vaccine with regard to efficacy also in seniors||in own facilities and at Unigen (Japan)||U.S. government||Pr.mitt. Sanofi/GSK, Pr.mitt. Sanofi, clinicaltrials.gov, FAZ.net|
|Genexine / Binex / GenNBio / Int. Vaccine Inst. / Korea Advanced Inst. of Science & Technology (KAIST) / Pohang Univ. of Science and Technology (POSTECH)||GX-19||DNA-based vaccine||in phase I/II since 17.06.2020 in South Korea||by Binex||n / a||inquirer.net, Korea Biomedical Review, Reuters|
|Spy Biotech/Serum Institute of India||RBD SARS-CoV-2 HBsAg VLP vaccine||Subunit vaccine with genetically engineered viral proteins||in phase I/II trial in Australia since 22.08.2020||n / a||n / a||ANZCTR|
|Institute of Medical Biology / Chinese Academy of Medical Sciences||n / a||Vaccine with inactivated virus||Phase I/II in China||tbd||n / a||WHO|
|Institut Pasteur / Themis (an MSD company) / Univ. of Pittburgh||V591 (TMV-083)||Vector virus vaccine (based on measles virus)||Phase I/II trial in France and Belgium, since 10/08/2020.||n / a||n / a||Clinicaltrials.gov|
|Serum Institute of India / Accelagen||tbd||Vaccine with virus-like particles from Receptor Binding Domain (RBD) SARS-CoV-2 and Hepatitis B Surface Antigen (HBsAg)||in Phase I/II trial in Australia since 22.08.2020||n / a||n / a||anzctr.org/au|
|Biological E (India)||n / a||Subunit vaccine using Receptor Binding Domain of SARS-CoV-2 as antigen.||Phase I/II study in India since 16.11.2020||n / a||by CEPI||CTRI, Pr.mitt. Biological E|
|Center for Genetic Engineering and Biotechnology (CIGB) (Cuba)||CIGB-669||Subunit vaccine||since 07.12.2020 in phase I/II study in Cuba||n / a||n / a||RPCEC|
|Center for Genetic Engineering and Biotechnology (CIGB) (Cuba)||CIGB-66||Subunit vaccine||in phase I/II trial in Cuba since 07.12.2020||n / a||n / a||RPCEC|
|Valneva (France and UK)||VLA2001||Vaccine with inactivated viruses, with adjuvant||in phase I/II trial, since 16.12.2020 in UK||at own plant in Livingston (UK)||Government of UK||Pr.mitt. of UK government, Pr.mitt. of UK government, Pr.mitt. Valneva|
|Shenzhen Geno-Immune Medical Institute||LV-SMENP-DC||Vaccine with dendritic cells||since 24.03.2020 in phase I/II in China||n / a||n / a||clinicaltrials.gov|
|Nanogen Biopharmaceutical (Vietnam)||Nanocovax||Subunit vaccine with recombinant antigen + adjuvant||Phase I/II study since 10.12.2020 in Vietnam||n / a||n / a||Nanogen, Nanogen|
|Shionogi||n / a||Subunit vaccine with viral antigen and adjuvant produced by genetic engineering (with baculoviruses)||Phase I/II study since approx. 15.12.2020 in Japan||by Api Co., Ltd, through its company UNIGEN Inc.||n / a||Pr.mitt. Shionogi|
|Imperial College London / VacEquity Global Health||LNP-nCoVsaRNA||RNA-based vaccine (with self-propagating RNA)||in Phase I; Phase III trial involving Indonesian medical institutions is planned||tbd; multiple manufacturers planned; formulation by Polymun (Austria)||Government of UK, COVID-19 Response Fund of Imperial College London Alumni, Morningside Ventures (Hong Kong)||Imperial College, Imperial College, Thomson Reuters Foundation News; Imperial College London, Imperial College London, Imperial College London, Polymun|
|Beijing Minhai Biotechnology||SARS-CoV-2 Vaccine (Vero Cells)||Vaccine with inactivated virus propagated in Vero cells||Phase I in China||tbd||n / a||WHO|
|Clover Biopharmaceuticals / GSK / Dynavax||SCB-2019||Subunit vaccine (antigen: genetically engineered trimeric spike protein; adjuvant: either from GSK or from Dynavax)||Phase I in Australia since mid-June with positive results; Phase II/III trial with GSK adjuvanted version of vaccine planned||in own facility in China||CEPI||Canberra Times, Reuters, Pr.mitt. Clover, Fierce, clinicaltrials.gov|
|Walvax Biotechnology / People's Liberation Army (PLA) Academy of Military Sciences / Suzhou Abogen Biosciences||ARCoV||mRNA-based vaccine||in phase I since 02.07.2020 in Adelaide, Australia||n / a||n / a||China Global Television Network Online|
|Vaxine (Australia) / Medytox / Flinders University (Australia)||COVAX-19||Inactivated vaccine with genetically engineered viral protein||Phase I (conducted in China) completed; Phase II planned||n / a||n / a||ABC News, News.com|
|ReiThera (Italy) / Leukocare (Germany) / Univercells (Belgium)||GRAd-COV2||Vector virus vaccine (Gorilla Adenoviral Vector)||in Phase I since 24.08., in Italy||in Belgium at Univercells||Italian Ministry of Research with the CNR and the Lazio Region||Pr.mitt. ReiThera/Leukocare/Univercells, Rainews, BioSpace, Pr.mitt. Reithera|
|Adimmune (Taiwan)||AdimrSC-2f||Subunit vaccine with adjuvant||In Phase I trial since Aug. 24, 2020 in Taiwan.||n / a||n / a||clinicaltrials.gov|
|COVAXX||UB-612 COVID-19 vaccine||Peptide-based vaccine (multitope vaccine)||in phase I trial in Taiwan since approx. 01.09.2020; phase I/II trials in the USA and phase II/III trials in Brazil planned||n / a||n / a||clinicaltrials.gov, Pr.Mitt. COVAXX; Pr.mitt. COVAXX|
|German Center for Infection Research (DZIF) / Univ. Munich / Univ. Marburg / UKE||MVA-SARS-2-S||Vector virus vaccine based on MVA viruses||In phase I trial since beginning of October at the University Hospital Eppendorf, Hamburg. Insufficient immunization was found. Possibilities for improvement are being sought.||at IDT Biologika (Dessau-Roßlau)||BMBF (supports production and study capacity)||Pr.mitt. of the consortium, Pr.Mitt. IDT Biologika, Mitteldeutsche Zeitung, Hamburger Morgenpost, clinicaltrials.gov; Pr.mitt. DZIF, NDR, Pr.mitt. DZIF|
|Vaxart||VXA-CoV2-1||tablet-based vector virus vaccine (based on adenovirus)||in Phase I since October in the USA||n / a||US government (Operation Warpspeed)||bioRXiv; Pr.mitt. Vaxart, clinicaltrials.gov|
|Medigen with National Institutes of Health (USA) and Dynavax||MVC-COV1901||Subunit vaccine with adjuvant CpG 1018||in Phase I in Taiwan||n / a||Government of Taiwan||AA, pipeline review|
|ImmunityBio / NantKwest||hAd5-S-Fusion+N-ETSD||Vector virus vaccine based on an adenovirus with two SARS-CoV-2 genes.||in phase I in the USA since 19.10.2020||n / a||n / a||Pr.mitt. ImmunityBio, clinicaltrials.gov|
|MSD and IAVI||V590||Vector virus vaccine based on the virus rVSV||in Phase I study in the USA since 30.10.2020||tbd||Defense Threat Reduction Agency (DTRA) of the U.S. Department of Defense, BARDA (U.S.), the Japanese government (planned), World Bank (planned).||Pr.mitt. MSD, IAVI, Pr.mitt. IAVI, clinicaltrials.gov|
|Symvivo (Canada)||bacTRL||Vaccine with genetically modified bifidobacteria||in Phase I trial in Australia||n / a||n / a||Symvivo|
|Instituto Finlay de Vacunas (Cuba)||FINLAY-FR-2 anti SARS-CoV-2||Inactivated vaccine with protein antigen chemically linked to tetanus toxoid||Phase I trial in Cuba since 02/11/2020.||n / a||n / a||Registro Público Cubano des Ensayos Clínicos|
|TC Erciyes University (Turkey)||ERUCOV-VAC||Vaccine with inactivated||Phase I study since 05.11.2020 in Turkey.||n / a||n / a||The Hindu Business Line, COVIDVAX|
|City of Hope Medical Center /National Cancer Institute of the USA||COH04S1||Vector virus vaccine based on MVA viruses||In phase I, since approx. 25.11.2020 in the U.S.||n / a||n / a||Pr.mitt. City of Hope|
|University Hospital Tübingen||P/T-pVAC-SARS-CoV-2||inactivated vaccine with SARS-CoV-2 HLA-DR peptides||in phase I, since 27.11.2020 in Tübingen||currently at the University of Tübingen||State government of Baden-Württemberg||State government of Baden-Württemberg, clinicaltrials.gov, Pr.mitt. University Hospital Tübingen|
|Codagenix||COVI-VAC||Live vaccine with attenuated SARS-CoV-2 viruses||Phase I study since 11.12.2020 in UK||n / a||n / a||clinicaltrials.gov|
|Shifa Pharmed (Iran)||Coviran||Vaccine with inactivated SARS-CoV-2 viruses||Phase I trial started in Iran on Dec. 29, 2020.||n / a||n / a||The Hindu|
|Kentucky Bioprocessing (USA)||KBP-COVID-19||Subunit-tot vaccine with genetically engineered antigens (produced in tobacco)||Phase I trial in the USA since December 2020||n / a||n / a||clinicaltrials.gov, Bloomberg, clinicaltrials.gov, Pr.mitt. BAT|
|Shenzhen Geno-Immune Medical Institute||Covid-19/aAPC vaccine||Vaccine with artificial antigen presenting cells (aAPCs)||since 15.02.2020 in phase I in China||n / a||n / a|
|Entos Pharmaceuticals||Covigenix VAX-001||DNA-based vaccine||Phase I study planned||n / a||n / a||clinicaltrials.gov|
|Chulalongkorn University (Thailand)||ChulaCov19||mRNA-based vaccine||Start of Phase I trial delayed as production is delayed||n / a||Fundraising campaign in the population of Thailand||Fortune, clinicaltrials.gov, International SOS, report Chulalongkorn University, clinicaltrials.gov|
|Providence Health & Services / OncoSec Medical Incorporated||CORVax||Vaccine with DNA plasmid containing gene for spike protein||Phase I study planned in the USA||n / a||n / a||clinicaltrials.gov|
|Aivita||n / a||Dendritic cell vaccine||Phase I study planned||n / a||n / a||clinicaltrials.gov|
|Altimmune||AdCOVID||Vector virus vaccine administered as a nasal spray||Phase I trial planned||n / a||n / a||biorxiv.org,Pr.mitt. Altimmuneclinicaltrials.gov|
|University Groningen / Akston Biosciences||AKS-452||Vaccine||Phase I/II study planned in the Netherlands||n / a||n / a||clinicaltrials.gov|
Only one vaccine project has been terminated prematurely after clinical trials: by University of Queensland and CSL. Although the vaccine stimulated the immune system in an appropriate way, it led to false positive results in HIV tests. This led to the decision to terminate the project.
Regulatory requirements for Covid 19 vaccines
An ideal Corona vaccine would achieve complete and lifelong protection against infection with SARS-CoV-2 in everyone vaccinated with it, with few and mild side effects. However, no vaccine will fully achieve this ideal goal.
For EU countries, the European Medicines Agency (EMA) is responsible for approving Covid 19 vaccines, but Member State authorities play a key role in the approval process. They have previously advised vaccine developers and approved clinical trials of vaccine candidates if they were to be conducted in their country.
The EMA, like the US Food and Drug Administration (FDA), insists first and foremost that Covid 19 vaccines are safe and that this has been convincingly demonstrated in large clinical trials. The FDA has announced that it will require an efficacy of at least 50 percent, meaning that no more than half as many of a larger group of vaccinated people will contract the disease as in a comparable group of unvaccinated people. The EMA has not yet made a determination in this regard. However, with their high efficacy rates of 95% and 94%, the first two vaccines submitted for approval have already far exceeded this threshold.
The EMA prioritizes all regulatory submissions for Covid 19 vaccines or therapeutics. In addition, the EMA offers a "rolling submission" option that allows companies to submit some chapters of their marketing authorization application for processing while the Phase III trial is still ongoing. Five companies (BioNTech/Pfizer, Moderna, AstraZeneca and Janssen) have already made use of this option.
The FDA and EMA, on the other hand, did not consider approval based on the results of Phase II trials. On September 8, 2020, nine Western pharmaceutical companies, which are already testing their vaccines with volunteers, also announced that they would not compromise on safety and ethical standards when testing their vaccines and would only apply for approval on the basis of Phase III results.
For the Phase III trials, the EMA, the FDA and other medicine regulatory authorities that are members of the ICMRA have agreed on a detailed list of requirements. According to this, several thousand participants are to be recruited for each of these trials, including people older than 55 years and those with concomitant diseases. Participants who have not yet been infected with SARS-CoV-2 are to be recruited in the main, and the degree of reliability of the vaccine is to be calculated only on the basis of their results. Nevertheless, the vaccine will also be tested with people who have already survived a SARS-CoV-2 infection. This is to ensure that there is no safety problem after approval if such individuals are also vaccinated. Whether or not pregnant women are eligible to participate in a particular Phase III trial will be decided on a case-by-case basis for each vaccine candidate, based primarily on animal test results. In all Phase III studies, interim evaluations are to be carried out in order to be able to identify possible risks or insufficient efficacy at an early stage, as well as the proof of efficacy that has been provided.
A vaccine can only be approved for minors if it has also been tested with them. However, most manufacturers will not start this process until the Phase III trial with adults has produced results on efficacy and tolerability that are suitable for approval. One exception is the company duo BioNTech/Pfizer, who have set up two arms with participants aged 12 to 18 years in their first Phase III study (one arm with the real vaccination, one arm with the sham vaccination). However, usable results from these arms are still pending, at least for participants under 16 years of age. For more on ongoing and planned vaccine trials with minors, see the article "How Covid-19 vaccines are being tested."
The first two covid-19 vaccines in the EU are therefore expected to be licensed only from 18 years of age or at most from 16 years of age.
The first companies and research institutes have already announced plans to expand their production capacity for a Covid-19 vaccine. Manufacturers Janssen (Johnson & Johnson), Kentucky BioProcessing, Moderna/Lonza, BioNTech/Pfizer as well as Oxford University, the Serum Institute of India, AstraZeneca and the ReiThera/Leukocare/Univercells consortium will furthermore already produce their vaccines on a large scale, while testing with volunteers is still ongoing - even at the risk of having to dispose of the produced goods if the study results turn out to be negative. CureVac announced in mid-May that it had already produced larger quantities of the main component of its active ingredient (mRNA) - although testing with volunteers has not even begun.
Production for world demand
Many companies have expanded their production capacities and recruited contract manufacturers to supply components or take over individual manufacturing steps.
Other companies not working on their own Covid 19 vaccine have offered to support the production of other companies' vaccines, such as Japan's Takeda.
In the UK, for its part, the development of the Vaccine Manufacturing and Innovations Centre in Oxfordshire is being accelerated. This non-commercial facility is expected to produce a vaccine against Covid-19 from the end of 2021. It will be partly government-funded, with Janssen, MSD and Cytiva as backers.
In the meantime, the availability of filling facilities and puncture vials has been identified as a possible bottleneck to supply. For this reason, the German government, for example, wants to support the expansion of such filling facilities with up to 250 million euros (in addition to vaccine development). As far as glassware is concerned, three major suppliers and the Coalition for Epidemic Preparedness (CEPI) (see below) have promised sufficient capacity.
Several manufacturers have announced that they will supply their vaccines against Covid-19 on a no-profit basis as long as the pandemic persists. The price is thus to be based on the costs incurred by the manufacturer itself.
Worldwide access to COVID-19 vaccines
The vaccines are needed in every country. On September 30, the Bill and Melinda Gates Foundation and 16 pharmaceutical and diagnostics companies countered concerns about focusing vaccine development solely on the needs and opportunities of the developed world with the statement "Commitments to Expanded Global Access for COVID-19 Diagnostics, Therapeutics, and Vaccines." Signatories are committed to developing innovations for patients worldwide, working toward affordability and rapid availability for all countries, supporting mechanisms for fair global resource allocation such as the COVAX Facility, and building confidence in Covid-19 vaccines (as well as therapeutics and diagnostics) by making user safety the paramount requirement for any product.
More on the COVAX Facility can be found here.
Types of vaccines
Companies and research institutes are working towards different vaccines. Most of their projects target one of the following three types of vaccines:
Live vaccines with vector viruses: Several projects use well-known, harmless viruses as a starting point, for example the "Modified Vaccinia Virus Ankara" (MVA), the adenovirus serotype 26 or the virus from measles vaccine. Such so-called vector viruses can multiply in humans without causing disease. It is also known how they can be produced in large quantities in cell cultures. Now researchers are adding one or more genes for surface proteins of SARS-CoV-2 to them. Some vector viruses are "disguised" in this way because they then carry these proteins themselves on their surface and can thus fool the immune system into thinking they have a Covid-19 infection. Other vector viruses do not look like SARS-CoV-2, but induce the production of the SARS-CoV-2 proteins in cells they have invaded. In both cases, this leads to the build-up of immune protection that can also fight off a real infection - or so the plan goes. Based in each case on a vector virus, the first licensed Ebola vaccines, the first dengue vaccine and other experimental vaccines have also been developed. Vector virus vaccines are now being developed by, for example, Janssen, the German Centre for Infection Research (DZIF), the University of Oxford with AstraZeneca, the IAVI / MSD collaboration and the ReiThera / Leukocare / Univercells consortium.
Inactivated Vaccines with Viral Proteins: These vaccines either contain selected viral proteins (such as at Novavax, Greffex, the University of Queensland, UMN Pharma (subsidiary of Shionogi) and Sanofi / GSK); or they contain the whole material of inactivated SARS-CoV-2 viruses (such as at Beijing Institute of Biological Products / Sinopharm). Thus, they are essentially based on long-proven technology: very many approved vaccines are composed in this way; for example, those against hepatitis B or influenza. However, it may be easier to produce large quantities of vaccine units quickly with other vaccines. However, this will only become clear when the time comes.
RNA vaccines: These vaccines contain a selected gene of the virus in the form of RNA, or more precisely, the form of RNA in which transcripts of individual genes that are required for protein production are produced in all living cells: messenger RNA (mRNA for short). After injection, the mRNA from the vaccine is supposed to induce the production of (harmless) viral protein in the body, which then in turn causes the build-up of immune protection, just as with a conventional vaccine. mRNA vaccines have the advantage that many injection doses can be produced from them very quickly. However, no such vaccine against any disease is yet on the market. Companies and institutes developing such vaccines against Covid-19 include BioNTech/Pfizer, Moderna, CureVac, Arcturus Therapeutics and eTheRNA. The way these vaccines work is explained in more detail in this video from #EUmythbusters.
- Similarly, vaccines that contain a piece of DNA with a viral gene instead of mRNA also work; the companies working on this include Inovio, the Genexine consortium and the OpenCorona consortium led by the Swedish Karolinska Institute and with the participation of the University of Giessen. So far, however, no DNA-based Covid 19 vaccine has progressed beyond Phase I.
There are also differences in the forms of application. Although most projects are aimed at injectable vaccines, there are exceptions:
- The Galilee Research Institute (MIGAL) and MigVax (both in Israel) are working on a dead vaccine (a subunit vaccine with chimeric antigens) that is placed in the mouth to act on immune cells in the mouth and throat.
- Argentina's National Scientific and Technical Research Councel (CONICET) is also working on an oral dead vaccine
- The company Vaxart (USA) is working on a vector virus vaccine that can be administered as a room temperature stable tablet, with release in the small intestine.
- The company's Altimmune vaccine is intended to be applied nasally, like a previously developed flu vaccine from the company.
- Bharat Biotech International and FluGen, as well as the University of Wisconsin-Madison (India/USA/USA), also plan to develop a nasal vaccine.
- A vaccine based on gene-modifying bifidobacteria from the Canadian company Symvivo is also to be applied nasally.
- Finally, the mRNA-based vaccine developed by the Belgian company eTheRNA in cooperation with EpiVax, Nexelis, REPROCELL and the Center for the Evaluation of Vaccination at the University of Antwerp will also be administered nasally.
The Coalition for Epidemic Preparedness Innovations (CEPI)
Several vaccine projects are financially supported by CEPI, the Coalition for Epidemic Preparedness Innovations. They are the projects of:
- CureVac (Tübingen, Germany)
- Inovio (USA) with the Wistar Institute (USA) and Beijing Advaccine Biotechnology (China)
- Moderna (USA) with the U.S. National Institute of Allergy and Infectious Diseases
- Novavax (USA)
- University of Queensland (Australia) with the company Dynavax and GSK, which contribute adjuvantsAdjuvants(1)
- University of Oxford (UK)
- Institut Pasteur, the company Themis (subsidiary of MSD ) and the University of Pittsburg (France / Austria / USA)
- University of Hong Kong (China)
- Clover Biopharmaceuticals Australia (subsidiary of Sichuan Clover Biopharmaceuticals, China)
- Biological E (India)
Product Development Partnerships
Product Development Partnerships (PDPs) are alliances that organize joint projects between foundations, government and aid organizations, and research groups and companies. The funds provided by the donors within the framework of a PDP are usually awarded to companies or research institutions in the form of fixed-term grants. PDPs can develop medicines that would be economically unfeasible for a single company to develop or that require readily available funding. This is because they ensure that the associated costs and economic risks are spread across the shoulders of several partners. This has already proven successful for new medicines against malaria, tuberculosis and sleeping sickness.
In conjunction with CEPI, the company GSK is also offering to contribute its own adjuvant technology for vaccines to projects for a SARS-CoV-2 vaccine. Thus, in addition to the aforementioned collaboration with the University of Queensland, there was also a cooperation with the Chinese vaccine developers Clover Biopharmaceuticals and Innovax Biotech as well as other companies and research institutes.
CEPI also took care of an early order of puncture bottles for the filling of the finished vaccines.
CEPI is a Product Development Partnership funded by Norway, Germany (Federal Ministry of Research), Japan, Canada, Australia and the Bill & Melinda Gates Foundation and Wellcome Trust, among others. It was established in 2017 specifically to coordinate, drive and financially support vaccine projects against major epidemics or pandemics.
What is what?
Coronavirens: family of viruses that infect humans or animals. It includes the pathogens that caused SARS in 2002/2003, MERS, several forms of the common cold and, of course, the currently rampant virus SARS-CoV-2.
SARS-CoV-2: Name given in February 2020 to the pathogen causing the current pandemic. It is often simply called "novel coronavirus." The abbreviation stands for Severe Acute Respiratory Syndrome-Coronavirus-2.
Covid-19:Fortunately, not every person who contracts SARS-CoV-2 becomes ill. Those who show symptoms after contracting the new pathogen suffer from the respiratory disease Covid-19, which derives its name from "coronavirus disease" and the year it first appeared, 2019.
Does a tuberculosis vaccination help against Covid-19?
It is possible that other vaccines can help to protect against infection, even though they were not developed against coronaviruses: Tuberculosis vaccines. The idea behind this: Vaccinations with these vaccines increase the general immune defence against germs and could therefore also help people to ward off SARS-CoV-2 or at least not to fall so seriously ill with it.
The suitability of the old tuberculosis vaccine BCG is to be tested at clinics in Nijmegen and Utrecht (Netherlands). This vaccine has not been used in Germany for a long time.
In Germany, the companies Vakzine Projekt Management (Germany) and Serum Institute of India are running trials to test the newer tuberculosis vaccine VPM1002, which has not yet been approved because final studies against tuberculosis are still ongoing. The Covid-19 trials are being conducted at several German clinics with the elderly and with healthcare workers. The vaccine was originally developed at the Max Planck Institute for Infection Biology in Berlin.
(1) are "boosters" for vaccines that, among other things, can allow significantly less viral protein per injection of vaccine to be sufficient for immunization or more doses of injection to be produced with a given amount of viral protein produced.