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. Four vaccines have now been approved in the EU, and partial registration dossiers have already been submitted for four others.

Vaccination campaign in Germany

Development projects for Covid 19 vaccines

Globally, at least 341 vaccine projects are moving forward (those for already approved vaccines included): the World Health Organization (WHO ) currently counts 329 (as of Nov. 30, 2021). In addition, there are at least twelve more projects that it does not yet list (1)

Vaccines against Covid-19: already approved, in the approval process or in the final phase of development (phase III)

Company / Research InstituteVaccineVaccine typeStatus of developmentFurther sources
BioNTech / Pfizer (Germany / USA)BNT162b2mRNA-based vaccineEU approval for adults and adolescents 16 years and older on 12/21/2020 after rolling review. EU approval for adolescents 12 years and older on 28.05.2021. Approvals and emergency approvals also in many other countries. EU approval for children aged 5 to 11 years has been applied for; in the USA it has already been granted on 29.10.2021 (emergency approval). Development and production was funded by the BMBF.The Wall Street Journal Entry EU Clinical Trials Register, Pr.mitt. Pfizer, Crain's Detroit Business, Pr.mitt. BioNTech, Pr.mitt. BioNTech, Pr.mitt. Rentschler Biopharma, Pr.mitt. BioNTech/Pfizer; Pr.mitt. BioNTech/Pfizer, tagesschau.de, Pr.mitt. BioNTech/Pfizer; Pr.mitt. BioNTech/Pfizer
Moderna (USA)mRNA-1273mRNA-based vaccineEU approval for adults on 06/01/2021 after rolling review. EU approval for adolescents 12 years and older on 07/23/2021. Approval also in US and other countries.ABC News, Bloomberg, Forbes, Reuters, Pr.mitt. Moderna, Fierce Pharma, FoxSanAntonio, The Shareholder, Pr. mitt. Moderna, BBC News, Pr. mitt. Moderna, EMA, Reuters
AstraZeneca Life Science / Oxford University (UK)ChAdOx1 nCoV-19 (AZD1222) or, if produced under license by Serum Institute of India: "Covishield".Vector virus vaccine (based on an adenovirus that cannot replicate in human cells)EU"approval" on 29.01.2021 after rolling review. Approvals and emergency approvals also in many other countries. Licensed version "Covishield" of the company Serum Institute of India approved in India since 02.01.2021 for "emergency use". No approval applied for minors yet.The Guardian Online, The Lancet, The Telegraph, inews, LiveScience, BBC, BBC, Statnews, Fiercepharma Reuters, Oxford University,Fierce Pharma, Pr.mitt. CSL, The Phuket News, NTV News, Pr.mitt. AstraZeneca, NTV, BBC, DAZ Online, Reuters, Pr.mitt. Novasep
Janssen (Johnson&Johnson)Ad26.COV2-SVector virus vaccineApproval in EU on 11/03/2021; following phase III trial since September 2020 and subsequent rolling review. In the US, emergency approval granted on 26/02/2021. At the EMA, parts of the marketing authorization application in "rolling submission" already submitted, but no complete marketing authorization application yet. Phase III trial ongoing in the US, Brazil, Chile, Colombia, Mexico, Peru, South Africa, Ukraine and the Philippines. Interim results from the trial show 66% efficacy in preventing moderate to severe Covid 19 disease (not: preventing all Covid 19 disease). A Phase II study in the Netherlands, Germany (UKE, Charité Berlin, Uniklinik Rostock) and Spain is also ongoing.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, Pr.mitt. Johnson&Johnson, Pr.mitt. Janssen
NovavaxNVX-CoV2373Inactivated vaccine with genetically engineered viral antigen (nanoparticle technology) and saponin-based adjuvantMarketing authorisation application submitted to EMA since 17.11.2021; study results (not yet peer-reviewed) have been published. Marketing authorisation application submitted in UK on 27.10.2021.Pr.mitt. Novavax, clinicaltrials.gov, Pr.mitt. Novavax, Novavax quarterly report, ABC News, Pr.mitt. Novavax
Natl. Gamaleya Research Center for Epidemiology and Microbiology (Russia), Ministry of Health of Russia / R-PharmGam-COVID-Vac = Sputnik VVector virus vaccine; uses different adenoviruses (Ad26 and Ad5) for the first and second vaccination, respectively.For EU in rolling review at EMA; i.e., parts of marketing authorization application submitted, as of 03.03.2021. Otherwise in phase III trial since 31.08.2020 in Russia and other countries. Has already been approved in Russia after phase II. Approvals also in Belarus and Argentina. Use also in Hungary (EU) and San Marino (non-EU). 91.6% efficacy according to Lancet publication on interim results of phase III trial 02.02.2021.Sputnik Germany, TASS, AA, Reuters, Reuters, GxP News, Lancet, Pr.mitt. EMA, faz.net
SinoVac BiotechCoronaVacVaccine with inactivated virusFor EU in rolling review at EMA; i.e. parts of marketing application submitted, as of 04.05.2021. Otherwise in phase III (partnership with Instituto Butantan); interim results from studies indicate reliability between 50% and 91%; Hungary has supply contract with SinoVac, according to media reports.Pr.mitt. Sinovac, Clinicaltrials.gov registry entry, CGTN, Fierce Pharma, clinicaltrials.gov, Reuters, Bangkok Post, BBC, CGTN, Pr.mitt. EMA
Valneva (Austria, France and UK)VLA2001Vaccine with inactivated viruses, with adjuvantFor EU in rolling review at EMA; i.e. parts of marketing authorisation application submitted, as of 02.12.2021. Otherwise in phase III trials: since April 2021 in UK, since August 2021 also in New Zealand; VLA2001 is compared therein with AstraZeneca's Covid-19 vaccine.Pr.mitt. of the UK government, Pr.mitt. of the UK government, Pr.mitt. Valneva, Pr.mitt. Valneva
Sanofi / GSKSP0253Inactivated vaccine with genetically engineered (baculovirus) antigen (CoV2 preS dTM monovalent D614 antigen) and adjuvant AS03For the EU in rolling review at the EMA; i.e. parts of the marketing authorisation application have already been submitted, on from 20.07.2021. Otherwise in phase III trial.Pr.mitt. Sanofi/GSK, Pr.mitt. Sanofi, clinicaltrials.gov, FAZ.net
Sinopharm / Wuhan Institute of Biological Products / Wuhan Institute of Virology of the Chinese Academy of Sciencesinactivated Novel Coronavirus Pneumonia (COVID-19) vaccine (Vero cells)Vaccine with inactivated virusin 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 a Dec. 29, 2020, release; it was licensed in China on Dec. 30Clinicaltrialsarena, ChiCTR, CGTN, Reuters, CNN, South China Morning Post
Beijing Institute of Biological Products / SinopharmtbdDead vaccine (inactivated viruses)in phase IIIWHO, Reuters, Asharq Al-Awsat
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 planned in Saudi Arabia; planned trial in Canada cancelledNature Reviews Drug Discovery, Clinicaltrials.gov registry entryPr.mitt. Natl. Research Councel Canada, Hindustan Times, Reuters, TrialSiteNews
Bharat Biotech / Indian Council of Medical Research / Natl. Institute of Virology (India)Covaxin (BBV152)Vector virus vaccineIn phase III in India since Nov. 12, 2020 (target: 26,000 participants); approved for "emergent use" in India since Jan. 02, 2021, although no efficacy results had been published at that timePr.mitt. Bharat Biotech, expresspharma.in, Zeenews, Reuters, NDTV, Hindustan Times
Anhui Zhifei Longcom Biopharmaceutical / Institute of Microbiology, Chinese Academy of Sciences.k. A.Subunit vaccine (antigen and adjuvant)in phase III since 30.11.2020CNBCTV18, CHICTR
Research Institute for Biological Safety Problems / Natl. Scientific Center for Phthisiopulmonology of the Republic of Kazakhstan (Kazakhstan)QazCovid-inVaccine with inactivated SARS-CoV2in phase III trial in Kazakhstan since 25.12.2020clinicaltrials.gov, clinicaltrials.gov
Zydus Cadila Healthcare (India)ZyCoV-DDNA-based vaccine (plasmid) to be administered intradermally three times and stored at 2 to 8 degrees Celsius.In Phase III since January 2021 in India with 28,000 volunteers; showed 67% efficacy against symptomatic Covid-19 infections in an interim evaluation. The vaccine has already been licensed in India.CTRI, Pr.mitt. Zydus Cadila, ThePrint, Livemint
Instituto Finlay de Vacunas (Cuba)FINLAY-FR-2 anti SARS-CoV-2Dead vaccine with protein antigen chemically linked to tetanus toxoidPhase III studyRegistro Público Cubano des Ensayos Clínicos
Vector Virology Institute (Russia)EpiVacCoronaInactivated vaccine with peptide antigensAfter phase III trial since November 2020 in Russia. Already approved in Russia. According to Russian news agency TASS on 19/01/2021 100% effective.Clinicaltrialsarena, clinicaltrials.gov, TASS, Reutersclinicaltrials.gov
Institute of Medical Biology / Chinese Academy of Medical Sciencesk. A.Vaccine with inactivated virusPhase III in ChinaWHO
Medicago (Canada) / GSKCoVLPInactivated virus vaccine with virus-like particles from antigens produced in plants and adjuvant from GSKsince 16.03.2021 in phase III in CanadaMedicago, Financial News, Pr.mitt. Medicago/GSK, Reuters
Center for Genetic Engineering and Biotechnology (CIGB) (Cuba)Abdala (= CIGB-66)Subunit vaccine (recombinant)In phase III trial in Cuba since March 2021; licensed there since July 2021; interim result: 92.28 % protection against symptomatic infectionsRPCEC, RPCEC
Clover Biopharmaceuticals / DynavaxSCB-2019Subunit vaccine (antigen: genetically engineered trimeric spike protein; adjuvants: Dynavax's CpG 1018 and aluminum salt).in Phase III part of a Phase II/III study with more than 30,000 participants, including in Germany and Poland. Efficacy results published: among others 79 % against delta variant. Submission of a marketing authorisation application to the EMA is planned.Canberra Times, Reuters, Pr.mitt. Clover, Fierce, clinicaltrials.gov
Valneva (Austria, France and UK)VLA2101Vaccine with inactivated variant of SARS-CoV-2 (unspecified), with adjuvant.In phase III trials, in New Zealand since August 2021; VLA2101 is being compared with VLA2001 (see above).Pr.mitt. Valneva
Shenzhen Kangtai Biological Products / Beijing Minhai Biotechnologyk. A.inactivated SARS-CoV-2 (produced with Vero cells)in phase IIIsince April 2021clinicaltrials.gov
Walvax Biotechnology / People's Liberation Army (PLA) Academy of Military Sciences / Suzhou Abogen BiosciencesARCoVmRNA-based vaccinein phase III since April 2021China Global Television Network Online, xinhuanet.com, clinicaltrials.gov
West China Hospital, Sichuan Universityrecombinant SARS-CoV-2 vaccine (Sf9 cell)Dead vaccine with genetically engineered protein antigen and adjuvantPhase III trial in China since 05/2021Chinese Clinical Trial Registry, clinicaltrials.gov
Nanogen Biopharmaceutical (Vietnam)NanocovaxSubunit vaccine with recombinant antigen + adjuvantPhase III trial since 07 June 2021 in VietnamNanogen, Nanogen, clinicaltrials.gov
TC Erciyes University / TÜBITAK (Scientific and Technologica Research Council of Turkey)TurkovacVaccine with inactivated SARS-CoV-2 viruses, with adjuvant.Phase III trial since June 2021 in TurkeyCOVIDVAX, AA
Vaxine (Australia) / Cinnagen (Iran)SpikogenVaccine with recombinant protein and adjuvant Advax-SMPhase III trial since August 2021Vaxine
SK Bioscience (South Korea) and CEPIGBP510Vaccine with viral protein in nanoparticles and adjuvant (AS03 from GSK)in Phase III in Korea since August 2021clinicaltrials.gov
Biological E (India)CORBEVAXprotein-based vaccine with adjuvant CpG 1018 from DynavaxPhase IIICTRI
Razi Vaccine and Serum Research Institute (Iran)Fakhravacprotein-based vaccinephase IIIk. A.
Inovio (USA)INO-4800DNA-based vaccine administered by electroporationIn Phase III WHO trial in Mali, Colombia and the Philippines(Solidarity Trial Vaccines) since October 2021, comparing multiple vaccines. Inovio is also preparing its own phase III trial.Pr.mitt. Inovio, Pr.mitt. Inovio/Advaccine
Medigen Vaccine Biologics (Taiwan)MVC-COV1901Protein-based vaccine (with trimeric spike protein) with the adjuvants aluminum hydroxide and CpG 1018 from DynavaxIn phase III WHO trial in Mali, Colombia and the Philippines(Solidarity Trial Vaccines)since October 2021, comparing multiple vaccines. Already approved and marketed in Taiwan.tbd
University of Hong Kong, Xiamen University and Beijing Wantai Biological Pharmacy (China)DelNS1-2019-nCoV-RBD-OPT1Influenza virus-based replication vector virus vaccine; nasally administered.Phase III since 10/28/2021k. A.
Livzon Pharmaceutical (China)V-01Protein-based vaccine with genetically engineered antigen (fusion protein)Phase III (for primary vaccination)Phase III (for booster vaccination)k. A.
Arcturus Therapeutics (USA)ARCT-154Vaccine with self-amplifying RNA; adapted to the Delta variant and other Variants of ConcernPhase III in VietnamArcturus
National Vaccine and Serum Institute (China)NVSI-06-08 + COVID-19 vaccine (Vero cells)protein-based vaccines with genetically engineered antigen (produced with Vero or CHO cells)in phase III trial since October 2021k. A.
AnGes (Japan) / Osaka University / Takara BioAG0302-COVID19DNA-based vaccine with adjuvantin phase II/III in Japan since 23 NovemberJapan Times, Japan Times, clinicaltrials.gov, clinicaltrials.gov
Shifa Pharmed (Iran)CoviranVaccine with inactivated SARS-CoV-2 virusesPhase II/III trial started in Iran in March 2021.The Hindu, Iranian Registry of Clinical Trials
Sinocelltech (China)SCTV01Cbivalent vaccine with spike proteins of multiple variants, for booster vaccinationPhase II/IIIclinicaltrials.gov
Israel Institute for Biological Research (Israel) and partnersBrilife (IIBR-100)Vaccine with replication-capable vector viruses based on vesicular stomatitis virus (VSV)Phase IIb/IIIk. A.
Jiangsu Rec-Biotechnology (China)ReCOVprotein-based vaccine with genetically engineered antigens (CHO)Phase II/IIIk. A.
KM Biologics (Japan)KD-414Vaccine with inactivated SARS-CoV-2 virusesPhase II/III since 21.10.2021k. A.

In addition, the WHO is considering whether the CODI-VAC vaccine from Codagenix/Serum Institute of India (USA/India), which is administered as a nasal drop, should also be tested as part of the Phase III "Solidarity Trial Vaccines" study. The vaccine contains replication-capable vector viruses based on influenza viruses. To date, it has completed a Phase I trial.

Ongoing projects in earlier stages of development can be found in the continuously updated table "COVID-19 Landscape of novel coronavirus candidate vaccine development worldwide" of the World Health Organization WHO.

Among others, these vaccine projects have been terminated prematurely after clinical trials: University of Queensland and CSL projects, Altimmune, MSD/Institute Pasteur/University of Pittsburgh, MSD/IAVI, Sanofi/Translate Bio, and CureVac. In one case, the vaccine appropriately stimulated the immune system but led to false positive results on HIV tests. Several other vaccines did not achieve a sufficiently strong immune response. In one case, the company decided not to complete development of its own mRNA vaccine in view of the competitive situation. In each case, this led to the decision to discontinue the project in question.

Regulatory requirements for Covid 19 vaccines

Production capacity and global access

The companies have made great efforts in parallel with clinical development to also enable large-scale production of their vaccines. There is more on this in the article"Expanding supply volumes for Covid-19 vaccines". The main organization for global distribution of the vaccines, especially to poorer countries, is the COVAX facility. More can be found here.

Types of vaccines

The first vaccines against covid-19 licensed in the EU are based on mRNA or vector viruses. Among the vaccines still in development, there are vaccines of the same type as well as vaccines that are still of a different type. Here is an overview of the most important vaccine types:

Schematische Darstellung des Virus, der Virusbestandteile im Impfstoff sowie im Körper, unterteilt nach Totimpfstoff, Vektorimpfstoff und RNA-Impfstoff

You can also download this chart as a PDF or as a JPG (free to use with attribution).

Vaccines with viral protein: These are also called subunit vaccines and are counted among the "dead vaccines" because they do not contain any living viruses. These vaccines contain a few micrograms of a selected protein from SARS-CoV-2. Technically, however, the protein is not obtained directly from the coronavirus, but is produced by genetic engineering. Examples are the vaccines from Novavax and Sanofi / GSK. Typically, vaccines with viral protein also contain an adjuvant that puts the immune system on alert immediately after vaccination. This makes the immune system particularly aware of the injected foreign protein and builds up a defence against it; this defence can then also fight the actual viruses. Vaccines containing viral protein have already proved effective against other diseases, such as hepatitis B and influenza (although here the protein is extracted directly from the viruses). So far, no vaccine with viral protein against covid-19 has been approved in the EU, but two are under rolling review by the EMA.


mRNA vaccines: these vaccines contain the associated gene for a viral protein instead of a selected viral protein; and they are in the form of an mRNA (messenger RNA) embedded in small vesicles (lipid nanoparticles) that protect them and allow them to enter cells. For cells, mRNAs are something commonplace; they constantly create mRNA transcripts of genes in the nucleus for themselves when they want to make the appropriate proteins. They use an externally supplied mRNA in the same way as they use their own: they use it several times to make the protein described in it and then degrade it. In this way, viral protein is produced in the body after vaccination, which then activates the immune system just as vaccines with viral protein do (well illustrated by #EUmythbusters). mRNA vaccines have the advantage that the manufacturing process is always the same, regardless of the pathogen; so you save development time for the production process.
Two mRNA vaccines against covid-19 are already licensed in the EU (by BioNTech/Pfizer and by Moderna). Others are in development.


DNA vaccines: Similar to mRNA vaccines, DNA vaccines are also expected to work. In these, the gene for a viral protein is contained on a piece of DNA (for example, on a DNA ring (= plasmid). After vaccination, the piece of DNA has to enter cells; and the cells then have to make transcripts from it into mRNA, which in turn are used to produce viral protein, which then works in the same way as a vaccine with viral protein. So there are even more steps involved in achieving the vaccine effect than with mRNA vaccines; and special inoculation devices are needed to get the DNA into the cells in the first place. One advantage over mRNA vaccines, however, is that DNA is more stable and DNA vaccines therefore require less refrigeration. In India, the company Zydus Cadila has received approval for the first DNA vaccine against covid-19, called ZyCoV-D (in fact, it is the world's first DNA vaccine ever); however, no EU approval has been applied for yet. Other DNA vaccines against Covid-19 are also in development. Inovio is currently testing its DNA vaccine in a WHO Phase III trial and is preparing its own Phase III trial (INNOVATE). The OpenCorona consortium, led by the Swedish Karolinska Institute and involving the Universities of Giessen and Tübingen, is also working on a DNA vaccine.

Forms of application

There are also differences in the forms of application. Although most projects are aimed at injectable vaccines, there are exceptions. For example, the development of vaccines that can be administered via the nose is linked to the hope of immunising people in such a way that they are not only protected against an outbreak of the disease themselves, but also that they can no longer infect anyone else with SARS-CoV-2. More on this can be found in the article"Next-generation corona vaccines".

In addition, there are also projects aimed at an orally applicable vaccine. Examples:

The Coalition for Epidemic Preparedness Innovations (CEPI).

Footnotes

(1) They are projects of the following companies and institutes:



(2) mRNA, DNA and vector virus vaccines are therefore sometimes grouped together as "gene-based vaccines"

(3) Product Development Partnerships (PDPs) are typically alliances of foundations, government and aid organizations, and research groups and companies. Funders in PDPs provide funds that are paid to companies or research institutions for projects on a fixed-term or performance-based basis. In PDPs, drugs can be developed that would be economically unfeasible for a single company or that require readily available funding. This is because they ensure that the project costs and economic risks are spread across the shoulders of several partners. This has already proven successful for new drugs against malaria, tuberculosis and sleeping sickness.