Vaccines to protect against Covid-19, the new coronavirus infection

Covid-19, the disease caused by the coronavirus SARS-CoV-2, affects people all over the world. However, companies and research institutes are developing protective vaccines.

195 vaccine projects against SARS-CoV-2, which has only been known since about New Year's Day, have been started within a short period of time: The World Health Organization WHO currently counts 187 (list from 21.09.2020). In addition, there are at least eight other projects that it has not yet listed. These are projects of the following companies and institutes:

Several companies have explicitly offered cooperation in the development of Covid 19 vaccines. GSK offered its adjuvants (i.e. potency-enhancing vaccine components) to all companies that could use them for their vaccines. This has led to a number of collaborations.

Status of vaccine development

Each project for a Covid 19 vaccine comprises seven parts, some of which are running in parallel. They are shown in the diagram below:

Presentation of the individual development steps of vaccines

Until a few years ago, it would have taken 15 to 20 years from virus analysis to approval of the vaccine. New technologies and previous experience with vaccine projects against related viruses (see below) are making an enormous acceleration possible. This is shown by the interim results that some companies and research groups have reported for their projects. Many have already started testing with volunteers or plan to do so in the coming months. This is shown in the following table (see below for explanations of the vaccine types):

Company / Research instituteVaccineType of vaccineTesting with volunteersProductionFinancial supportSources
Oxford University (UK) / AstraZeneca Life ScienceChAdOx1 nCoV-19 (AZD1222)Vector virus vaccine (based on an adenovirus that cannot replicate in human cells)in Phase III in Brazil (since end of June) and the USA (since the beginning of September)by AstraZeneca, Serum Institute of India, Halix, Pall Life Science, Cobra Biologics, Oxford Biomedica, SK Bioscience (South Korea), R-Pharm (Russia + Germany), Albany Molecular (USA) in future also in the British Vaccines Manufacturing and Innovations Centre (VMIC)CEPI, UK's Natl. Institute for Health Research, UK Research & Innovation, BARDA (USA)The Guardian Online, Message Merck, The Lancet, The Telegraph, inews, Live Science, BBC, BBC, clinicaltrials.gov, Statnews, Fiercepharma Reuters, Oxford University, Reuters, Fierce Pharma
Wuhan Institute of Biological Products / Wuhan Institute of Virology of the Chinese Academy of Sciences / Sinopharminactivated Novel Coronavirus Pneumonia (COVID-19) vaccine (Vero cells)Vaccine with inactivated virusin Phase III in China, the United Arab Emirates and Bahraintbdn / aClinical Trials Arena, ChiCTR, CGTN, Reuters
Sinovac BiotechCoronaVacVaccine with inactivated virusin phase III in Brazil since July 21, in partnership with Instituto Butantan; phase III study in Bangladesh approved from Augusttbdn / aPr.mitt. Sinovac, register entry Clinicaltrials.gov, CGTN, Fierce Pharma, clinicaltrials.gov, Reuters, Bangkok Post
Moderna (USA)mRNA-1273mRNA-based vaccinein phase III in the USA since 27 Julyby Lonza (in Portsmouth, New Hampshire [USA], and in Visp, Switzerland), bottling at Catalent (USA)CEPI, BARDAABC News, Bloomberg, Forbes, Reuters, Pr.mitt. Moderna, Pr.mitt. Moderna, Fierce Pharma, FoxSanAntonio, The Shareholder
BioNTech / Pfizer // BioNTech / Fosun PharmaBNT162b2mRNA-based vaccinePhase II/III study of BioNTech / Pfizer started on 27 July in the USA, later to be extended to Argentina and Germany (approval on 7 September 2020); first study of Fosun Pharma approved in Chinain Mainz / Idar-Oberstein / Marburg / Puurs (Belgium) / Kalamazoo (Michigan, USA) / Andover (Massachusetts, USA) / Chesterfield (Missouri, USA), also production step at Polymun (Austria)Horizon 2020 InnovFin, European Fund for Strategic Investments, BMBFPr.mitt. BioNTech, Pr.mitt. BioNTech/Pfizer, The Wall Street Journal Entry EU Clinical Trials Register, Pr.mitt. Pfizer, Pr.mitt. BioNTech/Pfizer, Crain's Detroit Business, Pr.mitt. BioNTech, Pr.Mitt. BioNTech/Pfizer, Mitteldeutsche Zeitung, Wiener Zeitung, Pr.mitt. BioNTech/Pfizer, Pr.mitt. BioNTech
Beijing Institute of Biological Products / SinopharmtbdDead vaccine (inactivated viruses)in phase IIIin own plantn / aWHO, Reuters, Asharq Al-Awsat
Natl. Gamaleya Research Centre for Epidemiology and Microbiology (Russia), Ministry of Health of RussiaGam-COVID-VacVector virus vaccine (Adenovirus)in Phase III trial in Russia since 31.08.n / an / aSputnik Germany, TASS, AA
CanSino Biologics (China) / Beijing Institute of Biotechnology, Academy of Military Medical Sciences, PLA of ChinaAd5-nCoVVector virus vaccine (Adenovirus type 5)in Phase III trials in Pakistan and Russia; trial in Saudi Arabia planned; planned trial in Canada cancelledwith the National Research Council of Canada (NRC) (cell line HEK293) in Montreal (Canada)Government of Canada (for production in Canada)Nature Reviews Drug Discovery, Register entry Clinicaltrials.govPr.mitt. Natl. Research Councel Canada, Hindustan Times, Reuters, TrialSiteNews
Janssen (Johnson&Johnson)Ad26.COV2-SVector virus vaccinein Phase III trial since 23 September in the USA, Brazil, Chile, Colombia, Mexico, Peru, South Africa, Ukraine and the Philippines. Meanwhile, the phase II study is ongoing in the Netherlands, Germany (UKE, Charité Berlin, University Hospital Rostock) and Spain.in own plants in Bümpliz (Switzerland) and Leiden (Netherlands) / by Catalent Biologics (USA) / supply of Emergent BioSolutions (USA) / supply of vaccine for clinical studies by Vibalogics (Cuxhaven)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
Imperial College London / VacEquity Global Healthn / aRNA-based vaccine (with self-proliferating RNA)in Phase II since July 17.tbd; several manufacturers are plannedGovernment of UK, COVID-19 Response Fund of the Alumni of Imperial College London, Morningside Ventures (Hong Kong)Imperial College, Imperial College, Thomson Reuters Foundation News; Imperial College London, Imperial College London, Imperial College London
NovavaxNVX-CoV2373Inactivated vaccine with genetically engineered virus antigen (nanoparticle technology) and saponin-based adjuvantsince August in Phase II in Australia, USA and South Africaby Emergent BioSolutions (USA) and in the future by subsidiary Praha Vaccines (Czech Republic)CEPI, US Government (Operation Warp Speed)Pr.mitt. Novavax, clinicaltrials.gov, Pr.mitt. Novavax, quarterly report Novavax, ABC News, Pr.mitt. Novavax, Handelsblatt
AnGes (Japan)AG0301-COVID19DNA-based vaccine with adjuvantaccording Media reports in Phase I/II since 30 Junethrough Takara Bio Inc. (Japan)n / aJapan Times, Japan Times, clinicaltrials.gov
Zydus Cadila Healthcare (India)ZyCoV-DDNA-based vaccine (plasmid)in Phase I/II since 14.07.2020, in Singaporen / an / aCTRI, News18
Inovio (USA)INO-4800DNA-based vaccine administered by electroporationsince 15 July in Korea in phase I/II study; phase II/III study planned in the USAby Richter-Helm BioLogics (Germany), VGXI (USA), Ology Bioservices (USA)CEPI, US Department of DefenseInovio, Inovio, Register entry Clinicaltrials.gov, Pr.mitt. Inovio
Arcturus Therapeutics (USA) / DukeNUS Medical School (Singapore)COVID-19 RIGID (ARCT-021)mRNA-based vaccine (self-replicating mRNA)Phase I/II study in Singapore since 04.08.by Catalent (USA)n / aPM Arcturus Therapeutics, quarterly report Arcturus Therapeutics, Pr.mitt. DukeNUS, clinicaltrials.gov
Instituto Finlay de Vacunas (Cuba)FINLAY-FR-1 anti SARS-CoV-2Inactivated vaccine with protein antigen and adjuvantPhase I/II study in Cuba since August 24n / an / aCuban Public Registry of the Ensayos Clinicos
Research Institute for Biological Safety Problems / Natl. Scientific Center for Phthisiopulmonology of the Republic of Kazakhstan (Kazakhstan)QazCovid-inVaccine with inactivated SARS-CoV2in Phase I/II trial in Kazakhstan since 01.09.n / an / aclinicaltrials.gov
Sanofi / GSKn / aInactivated vaccine with genetically engineered (with baculoviruses) antigen and adjuvantin Phase I/II trial in the USA since 03.09.in own plants and at Unigen (Japan)US GovernmentPr.mitt. Sanofi/GSK, Pr.mitt. Sanofi, clinicaltrials.gov
Institute of Medical Biology / Chinese Academy of Medical Sciencesn / aVaccine with inactivated virusPhase I in Chinatbdn / aWHO
CureVacCVnCoVmRNA-based vaccinePhase I study in Germany and Belgium; phase II in preparationin its own plant in Tübingen; Tesla will build mobile production facilitiesCEPI, EU Commission, Federal Government (KfW Bank)Pr.mitt. CureVac, border echo, pr.mitt. CureVac, pr.mitt. CureVac, dpa, pr.mitt. CureVac, Fierce Pharma, Mitteldeutsche Zeitung
Clover Biopharmaceuticals / GSK / DynavaxSCB-2019Inactivated vaccine (antigen: genetically engineered trimeric spike protein; adjuvant: either from GSK or Dynavax)Phase I since mid-June in Australiain own plant in ChinaCEPICanberra Times, Reuters
Genexine / Binex / GenNBio / Int. Vaccine Inst. / Korea Advanced Inst. of Science & Technology (KAIST) / Pohang Univ. of Science and Technology (POSTECH)GX-19DNA-based vaccineaccording Media reports in phase I in South Korea since 19 Junethrough Binexn / ainquirer.net, Korea Biomedical Review, Reuters
Anhui Zhifei Longcom Biopharmaceutical / Institute of Microbiology, Chinese Academy of Sciencesn / aSubunit vaccine (antigen and adjuvant)according WHO in Phase I since mid-Junen / an / aCNBCTV18
Walvax Biotechnology / People's Liberation Army (PLA) Academy of Military Sciences / Suzhou Abogen BiosciencesARCoVmRNA-based vaccinein Phase I since July 2 in Adelaide, Australian / an / aChina Global Television Network Online
Vaxine (Australia) / Medytox / Flinders University (Australia)COVAX-19Inactivated vaccine with genetically engineered virus proteinin Phase I (conducted in China) completed; start of Phase II planned for Septembern / an / aABC News, News.com
University of Queensland / GSK / Dynavax / CSLn / aInactivated vaccine with genetically engineered viral antigen and adjuvantin Phase I since 13 Julywith Cytiva and CLSCEPI, Queensland State Government, Federal Government of Australia, Paul Ramsay Foundation, Newcrest Mining, CSLUQ News, ABC News, Canberra Times, pipelinereview.com, 9news, Advance Queensland
Bharat Biotech / Indian Council of Medical Research / Natl. Institute of Virology (India)CovaxinVector virus vaccinein Phase I in India since 14.07.2020n / an / aPr.mitt. Bharat Biotech, expresspharma.in
Medicago (Canada)n / aInactivated vaccine with virus-like particles from antigens produced in plants, in the test with two different adjuvants from GSK and Dynavaxin Phase I since 14.07.2020, in Canadan / an / aMedicago, Financial News
Vector Virology Institute (Russia)n / aInactivated vaccine with peptide antigensin phase I since 27.07., in Russian / an / aClinicaltrials Arena
Institute Pasteur / Themis (an MSD company) / Univ. of Pittburghn / aVector virus vaccine (based on measles virus)Phase I study in France (later also Belgium) since 10 August.n / an / aClinicaltrials.gov
ReiThera (Italy) / Leukocare (Germany) / Univercells (Belgium)GRAd-COV2Vector virus vaccine (gorilla adeonoviral vector)in phase I since 24.08., in Italyin Belgium with UnivercellsItalian Ministry of Research with the CNR and the Lazio RegionPr.mitt. ReiThera/Leukocare/Univercells, Rainews, BioSpace
West China Hospital, Sichuan Universityrecombinant SARS-CoV-2 vaccine (Sf9 cell)Inactivated vaccine with genetically engineered protein antigen and adjuvantPhase I trial in China since 28 August.n / an / aChinese Clinical Trial Registry
Beijing Wantai Biological Pharmacy / Xiamen Universityn / aVector virus vaccine based on influenza viruses (intranally applicable spray)in Phase I trial in China since approx. 01.09.n / an / a
COVAXXUB-612 COVID-19 vaccinePeptide-based vaccine (multitope vaccine)in Phase I study in Taiwan since approx. 01.09.; Phase I/II studies in the USA and Phase II/III studies in Brazil plannedn / an / aclinicaltrials.gov, Pr.Mitt. COVAXX; Pr.Mitt. COVAXX
 
 
Symvivo (Canada)bacTRLVaccine with genetically modified bifidobacteriaStudy approved but not yet startedn / an / aSymvivo
Kentucky Bioprocessing (USA)KBP-COVID-19Inactivated vaccine with genetically engineered antigens (produced in tobacco)Study approved but not yet startedn / an / aclinicaltrials.gov, Bloomberg, clinicaltrials.gov
Vaxartn / aVector virus vaccine applicable as a tablet (based on an adenovirus)Phase I planned from the end of September in the USAn / aUS Government (Operation Warpspeed)bioRXiv; Pr.mitt. Vaxart
German Centre for Infection Research (DZIF) / Univ. Munich / Univ. Marburg / UKEn / aVector virus vaccine based on MVA virusesplanned from end of September at UKE (University Medical Center Eppendorf, Hamburg)at IDT Biologika (Dessau)BMBF (supports production and study capacity)Pr.mitt. of the consortium, Pr.Mitt. IDT Biologika, Mitteldeutsche Zeitung, Hamburger Morgenpost
University Hospital TübingenP/T-pVAC-SARS-CoV-2Inactivated vaccine with SARS-CoV-2 HLA-DR peptidesPhase I planned (Tübingen)n / aState Government of Baden-WürttembergState Government of Baden-Württemberg, clinicaltrials.gov
Chulalongkorn University (Thailand)n / amRNA-based vaccineStart according to media report planned for Septembern / an / aFortune
IAVI and MSDn / aVector virus vaccine based on the virus rVSVplanned for the second half of 2020tbdBARDA (USA)Pr.mitt. MSD

Requirements for a corona vaccine

An ideal corona vaccine would provide complete and lifelong protection against SARS-CoV-2 infection with few and mild side effects for anyone who is vaccinated with it. However, no vaccine will be able to fully achieve this ideal goal.

For EU countries, the European Medicines Agency (EMA) is responsible for the approval of Covid-19 vaccines, but the authorities in the Member States play a key role in the approval process. They have previously advised vaccine developers and approved clinical trials with vaccine candidates if these were to be carried out in their country.

The EMA, like the US Food and Drug Administration (FDA), insists first and foremost that Covid-19 vaccines are safe and this has been convincingly proven in large clinical trials. The FDA has announced that it will require an efficacy rate of at least 50 percent, which means that a larger group of vaccinated people will only infect half as many people with the disease as a comparable group of unvaccinated people. The EMA has not yet committed itself in this regard.

A shortening of the study program for Covid-19 vaccines, i.e. approval already with the results of Phase II studies, is not an option for either regulatory authority. However, the FDA has indicated that it may grant a special approval for a vaccine based on positive Phase III data in an expedited procedure in the event of a pandemic. The EMA has announced that it will give priority to all approval procedures for Covid 19 vaccines or therapeutics and has already done so for a first Covid 19 medicine. However, at the beginning of September there was a discussion in the USA and UK whether approval or emergency use of vaccines should be considered even without available Phase III results.

On 8th September 2020, nine Western pharmaceutical companies, which are already testing their vaccines with volunteers, also issued a statement in which they announced that they will not compromise on safety and ethical standards when testing their vaccines and will only apply for approval on the basis of Phase III results.

The EMA, the FDA and other medicines authorities associated in ICMRA have agreed on a detailed catalogue of requirements for the phase III studies. According to this catalogue, several thousand participants are to be recruited for each of these trials, including people over 55 years of age and those with concomitant diseases. Participants who have not yet been infected with SARS-CoV-2 will be recruited primarily, and only their results will be used to calculate the degree of reliability of the vaccine. Nevertheless, the vaccine will also be tested in people who have already survived SARS-CoV-2 infection. This is to ensure that there is no safety problem after approval if such persons are also vaccinated. Whether or not pregnant women are eligible to participate in a particular Phase III study will be decided individually for each vaccine candidate, based primarily on animal studies. All Phase III studies will be subject to interim evaluations in order to identify potential risks or insufficient efficacy at an early stage.

Testing will reveal which vaccine candidates come how close to the target values for an ideal vaccine. This, along with the expected month of regulatory submissions, will be a key factor in determining which vaccine projects the international funding will focus on. The WHO is currently setting up an advisory committee to evaluate the results of animal experiments and interim results from clinical studies.

When can a vaccine be expected?

How quickly vaccination campaigns can be started depends not only on the speed of vaccine development, testing and approval, but also on production capacities. Therefore, it is not decisive which vaccine reaches approval first, but that as many vaccines as possible reach approval and can be produced using many production facilities.

First companies and research institutes have already announced to expand their production capacities for a Covid-19 vaccine. The manufacturers Janssen (Johnson & Johnson), Kentucky BioProcessing, Moderna/Lonza, BioNTech/Pfizer as well as Oxford University, the company Serum Institute of India, AstraZeneca and the consortium ReiThera/Leukocare/Univercells will also produce their vaccines on an industrial scale while the testing with volunteers is still ongoing - even at the risk of having to dispose of the produced goods if the study results turn out negative. In mid-May, CureVac announced that it had already produced larger quantities of the major component of its active substance (mRNA) - although testing with volunteers has not even begun.

Other companies which do not have their own Covid 19 vaccine have offered to support the production of vaccines by other companies, such as Takeda of Japan.

In the UK, the establishment of the Vaccine Manufacturing and Innovations Centre in Oxfordshire is being accelerated. This non-commercial facility is to produce a vaccine against Covid-19 from the end of 2021. It is partly funded by the government, with the companies Janssen, MSD and Cytiva as supporters.

The availability of filling equipment and puncture vials was identified as a possible bottleneck for supply. For this reason, the German government, for example, wants to support the expansion of such filling plants (in addition to vaccine development) with up to 250 million euros. As far as glassware is concerned, three major suppliers and the Coalition for Epidemic Preparedness (CEPI) (see below) have promised sufficient capacity.

The targets for production are high. For example, Janssen (Johnson & Johnson) plans to produce 1 billion vaccine doses. Sanofi and GSK also plan to produce 1 billion vaccine doses. The same quantity, and this annually, is also the goal of Moderna and Lonza. CureVac is already able to supply several hundred million doses per year with its existing production plant, and another plant is yet to be built. AstraZeneca plans to deliver 30 million vaccine doses to the UK and 300 million doses to the US as early as September and October 2020 respectively.

Several manufacturers have announced that they will supply their vaccines against Covid-19 on a no-profit basis as long as the pandemic lasts; specifically AstraZeneca, GlaxoSmithKline, Pfizer (with BioNTech) and Janssen (subsidiary of Johnson & Johnson). The price should therefore be based on the costs incurred by the producer himself.

The "Inclusive Vaccine Alliance" - a coalition of the governments of France, Germany, Italy and the Netherlands announced on June 3, 2020 - wants to work to ensure that vaccines are developed even faster and (wherever possible) produced at locations in the EU. These vaccines will then be available at affordable conditions throughout the EU, as well as in poorer countries such as Africa. The aim is to work towards this goal with a joint strategy and joint investments and is open for other countries to join in. The alliance has also already concluded a supply agreement with one company.

Types of vaccines

The companies and research institutes are working towards different vaccines. Most of their projects are aimed at one of the following three types of vaccines:

Schematic diagram of the virus, the virus components in the vaccine and in the body after vaccination, divided into  vaccine with viral proteins, viral-vector vaccine and RNA vaccine

You can also download this chart as a PDF file.

Live vaccines with vector viruses: Several projects are based on well known, harmless viruses, such as 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. Researchers are now adding one or more genes for surface proteins of SARS-CoV-2, which "disguises" some vector viruses as they themselves carry these proteins on their surface and can thus make the immune system believe they are infected with Covid-19. Other vector viruses do not look like SARS-CoV-2, but induce the production of SARS-CoV-2 proteins in cells into which they have entered. In both cases, this leads to the establishment of an immune protection that can also fend off a real infection - this is the plan. In each case, the first approved Ebola vaccines, the first dengue vaccine and other experimental vaccines have also been developed based on a vector virus. Vector virus vaccines are now being developed by Janssen, the German Centre for Infection Research (DZIF), the University of Oxford with AstraZeneca, the IAVI / MSD cooperation and the ReiThera / Leukocare / Univercells consortium, for example.


Inactivated vaccines with viral proteins: These vaccines either contain selected viral proteins (e.g. Novavax, Greffex, the University of Queensland, UMN Pharma (subsidiary of Shionogi) and Sanofi / GSK); or they contain all the material of inactivated SARS-CoV-2 viruses (e.g. Beijing Institute of Biological Products / Sinopharm). Thus, they are essentially based on long-proven technology: a large number of 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 apparent when the time comes.


mRNA/DNA-based vaccines: These vaccines contain selected genes of the virus in the form of mRNA (= messenger RNA) or DNA. After injection, these genes are supposed to induce the formation of (harmless) viral proteins in the body, which in turn, as with a conventional vaccine, build up the immune protection. Such mRNA- and DNA-based vaccines have the advantage that many injection doses can be produced very quickly. However, no vaccine against any disease is yet available on the market. The companies and institutes developing such vaccines against Covid-19 include CureVac, BioNTech, Moderna, Inovio, Arcturus Therapeutics, LineaRx/Takis, AnGes, Translate Bio with Sanofi, eTheRNA and the Thai National Vaccine Institute with Chulalongkorn University; the OpenCorona consortium led by the Swedish Karolinska Institute and involving the University of Giessen is also developing a DNA-based vaccine.


Forms of application


There are also differences in the forms of application. Although most projects are aimed at injectable vaccines, there are exceptions:

The Coalition for Epidemic Preparedness Innovations (CEPI)

Several vaccine projects are financially supported by CEPI, the Coalition for Epidemic Preparedness Innovations. These are the projects of:

Das Bild zeigt eine symbolische Impfstoffflasche mit der Aufschrift Coronavirus Vaccine sowie eine Spritze, beides gehalten von einer Hand, die einen blauen Schutzhandschuh trägt.

Will a tuberculosis vaccination against Covid-19 help?

It is possible that other vaccines might be able to contribute to the protection against infection, although they were not developed against corona viruses: Tuberculosis vaccines. The idea behind them: Vaccinations increase the general immune defence against germs and could therefore also help people to fend off SARS-CoV-2 or at least not to fall ill with it so severely.

The suitability of the old tuberculosis vaccine BCG will 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 conducting studies to test the newer Tuberculosis vaccine VPM1002, which has not yet been approved because the last studies against Tuberculosis are still ongoing. The Covid-19 studies are being carried out at several German hospitals with elderly people and with health care workers. The vaccine was originally developed at the Max Planck Institute for Infection Biology in Berlin.

(1) are 'potentiators' for vaccines, which can, among other things, make it possible that considerably less viral protein per vaccine injection is sufficient for immunisation or that more injection doses can be produced with a given amount of viral protein produced.