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
In Germany, as in most EU countries, vaccination is carried out exclusively with Covid-19 vaccines, which have received approval from the EU Commission after being reviewed by the European Medicines Agency (EMA). The Federal Government provides information on the vaccine deliveries that have arrived and the status of vaccination in Germany with its vaccination dashboard
The repertoire of vaccines that can be used in this country is likely to expand in the coming months, as further applications for approval at the EMA are being processed or have been announced. And globally, there are still many more vaccines in development and some already approved nationally than will reach the EU market.
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)
The vfa provides information on the development status of Covid-19 vaccines for adolescents and children here
While most projects are still working on a first-generation vaccine, some companies and institutes are already working on second-generation vaccines that will provide even better protection against new SARS-CoV-2 variants or ensure that vaccinated individuals no longer transmit the virus - even symptom-free. This is explained in a separate article.
Development and production of Covid-19 vaccines in Germany
Germany is one of the countries with a particularly large number of Covid-19 vaccine projects internationally, 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 in this country:
- the companies BioNTech / Pfizer (Mainz, Marburg), two projects
- the company CureVac (Tübingen) in cooperation with GSK (UK)
- Leukocare (Planegg) with ReiThera (Italy) and Univercells (Belgium) - vector virus vaccine tested in a phase II trial in Italy.
- the start-up Prime Vector Technologies (PVT) (Tübingen) - vector virus vaccine
- ARTES Biotechnology (Langenfeld, Rhineland) - vaccine with virus-like particles (VLP)
- the start-up Belyntic (Berlin) in cooperation with the University of Bonn - peptide vaccine
- Daiichi Sankyo Europe (Pfaffenhofen) in cooperation with the University of Munich - RNA vaccine
- Bavarian Nordic (Planegg) in the PREVENT-nCoV consortium - cVLP vaccine ABNCoV2 (explicit goal: EU approval)
- the German Center for Infection Research (Braunschweig) / University of Munich / University of Marburg / UKE Hamburg / IDT Biologika (Dessau-Roßlau) - MVA-based vaccine MVA-SARS-2-ST, which is currently being tested in an improved form with volunteers in a phase I study
- Once again, the German Centre for Infection Research (Braunschweig) and IDT Biologika (Dessau-Roßlau), but now together with the Cluster of Excellence RESIST at the Hanover Medical School - they are developing an MVA-based vector virus vaccine for inhalation; a clinical phase I trial is being prepared for it
- University Hospital Tübingen - peptide vaccine CoVac-1 specifically for patients undergoing cancer treatment or otherwise suffering from immunodeficiency, currently in Phase II
- The start-up baseclick (Neuried near Munich) - mRNA-based vaccine
- the research project ContiVir of the Max Planck Institute for Dynamics of Complex Technical Systems in Magdeburg - VLP vaccine
- the project of the University of Würzburg with Aeterna Zentaris for an oral vaccination based on live oral typhoid vaccine
- In addition, a vector vaccine against covid-19 based on replication-incompetent Sendai viruses, which can be administered as a nasal spray, is being developed at the University Hospital in Tübingen in cooperation with the Department of Molecular Medicine at the Max Planck Institute of Biochemistry in Martinsried ( consortium). The project leaders anticipate about two years of development time before possible approval. This second-generation vaccine is designed to block any replication of SARS-CoV-2 in the respiratory tract of vaccinated individuals and thus completely prevent a vaccinated individual from infecting others.
In addition, the following companies and research institutes are supporting the development or production of the vaccine:
- Rentschler Biopharma (Laupheim): takes over the purification of the vaccine from BioNTech/Pfizer
- Dermapharm (Brehna): participates in the production of the vaccine of BioNTech/Pfizer
- Allergopharma (Reinbek) participates in the production of the BioNTech/Pfizer vaccine (production step formulation)
- Siegfried (Hameln): involved in the filling and packaging of the BioNTech/Pfizer vaccine and, in the future, also of the Novavax vaccine
- Sanofi (Frankfurt a.M.) is involved in the filling of BioNTech/Pfizer vaccine as well as in the filling of Sanofi/GSK vaccine
- IDT Biologika (Dessau-Roßlau) is involved in the filling of Janssen's vaccine and will build up additional production capacity for AstraZeneca
- Vibalogics (Cuxhaven): produces component for Janssen vaccine
- Richter-Helm BioLogics (Bovenau): produces DNA material for Inovio (USA); expansion of production capacity in preparation
- WuXi (Wuppertal): has been involved in the production of AstraZeneca's vaccine since the beginning of December 2021
- R-Pharm Germany (Illertissen), subsidiary of the Russian company R-Pharm: will produce AstraZeneca 's vaccine under license in the future and also the Russian vaccine Sputnik V
- Celonic (Heidelberg) will produce the vaccine of the Dutch company Intravacc
- Probiogen (Berlin) will optimize the manufacturing process for the Russian vaccine Sputnik V for production by Egyptian company Minapharm Pharmaceuticals
- Merck (Darmstadt, Germany): contributes to around 50 Covid 19 vaccine development and production projects worldwide; also produces lipids for BioNTech/Pfizer vaccine
- Recipharm (Wasserburg): develops production processes for another company
- Lipoid: supplies phospholipids for the production of mRNA vaccines
- Evonik has been producing lipids for BioNTech/Pfizer's mRNA vaccine since April 2021 in Hanau and in future also in Dossenheim (previously only in Canada)
- University of Giessen: participates in the OpenCorona consortium (led by the Karolinska Institute, Sweden), which is developing a DNA-based vaccine.
- Tropical Institute of the University of Tübingen: will test the dead vaccine of the Danish-Dutch-German PREVENT-nCoV consortium.
Vaccines against Covid-19: already approved, in the approval process or in the final phase of development (phase III)
|Company / Research Institute||Vaccine||Vaccine type||Status of development||Further sources|
|BioNTech / Pfizer (Germany / USA)||BNT162b2||mRNA-based vaccine||EU 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-1273||mRNA-based vaccine||EU 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-S||Vector virus vaccine||Approval 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|
|Novavax||NVX-CoV2373||Inactivated vaccine with genetically engineered viral antigen (nanoparticle technology) and saponin-based adjuvant||Marketing 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-Pharm||Gam-COVID-Vac = Sputnik V||Vector 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 Biotech||CoronaVac||Vaccine with inactivated virus||For 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)||VLA2001||Vaccine with inactivated viruses, with adjuvant||For 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 / GSK||SP0253||Inactivated vaccine with genetically engineered (baculovirus) antigen (CoV2 preS dTM monovalent D614 antigen) and adjuvant AS03||For 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 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 a Dec. 29, 2020, release; it was licensed in China on Dec. 30||Clinicaltrialsarena, ChiCTR, CGTN, Reuters, CNN, South China Morning Post|
|Beijing Institute of Biological Products / Sinopharm||tbd||Dead vaccine (inactivated viruses)||in phase III||WHO, Reuters, Asharq Al-Awsat|
|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||Nature 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 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 no efficacy results had been published at that time||Pr.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 30.11.2020||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||clinicaltrials.gov, clinicaltrials.gov|
|Zydus Cadila Healthcare (India)||ZyCoV-D||DNA-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-2||Dead vaccine with protein antigen chemically linked to tetanus toxoid||Phase III study||Registro Público Cubano des Ensayos Clínicos|
|Vector Virology Institute (Russia)||EpiVacCorona||Inactivated vaccine with peptide antigens||After 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 Sciences||k. A.||Vaccine with inactivated virus||Phase III in China||WHO|
|Medicago (Canada) / GSK||CoVLP||Inactivated virus vaccine with virus-like particles from antigens produced in plants and adjuvant from GSK||since 16.03.2021 in phase III in Canada||Medicago, 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 infections||RPCEC, RPCEC|
|Clover Biopharmaceuticals / Dynavax||SCB-2019||Subunit 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)||VLA2101||Vaccine 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 Biotechnology||k. A.||inactivated SARS-CoV-2 (produced with Vero cells)||in phase IIIsince April 2021||clinicaltrials.gov|
|Walvax Biotechnology / People's Liberation Army (PLA) Academy of Military Sciences / Suzhou Abogen Biosciences||ARCoV||mRNA-based vaccine||in phase III since April 2021||China Global Television Network Online, xinhuanet.com, clinicaltrials.gov|
|West China Hospital, Sichuan University||recombinant SARS-CoV-2 vaccine (Sf9 cell)||Dead vaccine with genetically engineered protein antigen and adjuvant||Phase III trial in China since 05/2021||Chinese Clinical Trial Registry, clinicaltrials.gov|
|Nanogen Biopharmaceutical (Vietnam)||Nanocovax||Subunit vaccine with recombinant antigen + adjuvant||Phase III trial since 07 June 2021 in Vietnam||Nanogen, Nanogen, clinicaltrials.gov|
|TC Erciyes University / TÜBITAK (Scientific and Technologica Research Council of Turkey)||Turkovac||Vaccine with inactivated SARS-CoV-2 viruses, with adjuvant.||Phase III trial since June 2021 in Turkey||COVIDVAX, AA|
|Vaxine (Australia) / Cinnagen (Iran)||Spikogen||Vaccine with recombinant protein and adjuvant Advax-SM||Phase III trial since August 2021||Vaxine|
|SK Bioscience (South Korea) and CEPI||GBP510||Vaccine with viral protein in nanoparticles and adjuvant (AS03 from GSK)||in Phase III in Korea since August 2021||clinicaltrials.gov|
|Biological E (India)||CORBEVAX||protein-based vaccine with adjuvant CpG 1018 from Dynavax||Phase III||CTRI|
|Razi Vaccine and Serum Research Institute (Iran)||Fakhravac||protein-based vaccine||phase III||k. A.|
|Inovio (USA)||INO-4800||DNA-based vaccine administered by electroporation||In 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-COV1901||Protein-based vaccine (with trimeric spike protein) with the adjuvants aluminum hydroxide and CpG 1018 from Dynavax||In 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-OPT1||Influenza virus-based replication vector virus vaccine; nasally administered.||Phase III since 10/28/2021||k. A.|
|Livzon Pharmaceutical (China)||V-01||Protein-based vaccine with genetically engineered antigen (fusion protein)||Phase III (for primary vaccination)Phase III (for booster vaccination)||k. A.|
|Arcturus Therapeutics (USA)||ARCT-154||Vaccine with self-amplifying RNA; adapted to the Delta variant and other Variants of Concern||Phase III in Vietnam||Arcturus|
|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 2021||k. A.|
|AnGes (Japan) / Osaka University / Takara Bio||AG0302-COVID19||DNA-based vaccine with adjuvant||in phase II/III in Japan since 23 November||Japan Times, Japan Times, clinicaltrials.gov, clinicaltrials.gov|
|Shifa Pharmed (Iran)||Coviran||Vaccine with inactivated SARS-CoV-2 viruses||Phase II/III trial started in Iran in March 2021.||The Hindu, Iranian Registry of Clinical Trials|
|Sinocelltech (China)||SCTV01C||bivalent vaccine with spike proteins of multiple variants, for booster vaccination||Phase II/III||clinicaltrials.gov|
|Israel Institute for Biological Research (Israel) and partners||Brilife (IIBR-100)||Vaccine with replication-capable vector viruses based on vesicular stomatitis virus (VSV)||Phase IIb/III||k. A.|
|Jiangsu Rec-Biotechnology (China)||ReCOV||protein-based vaccine with genetically engineered antigens (CHO)||Phase II/III||k. A.|
|KM Biologics (Japan)||KD-414||Vaccine with inactivated SARS-CoV-2 viruses||Phase II/III since 21.10.2021||k. 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
Why a vaccine cannot be developed without approved clinical trials was explained by immunologist Markus Löffler of the University Hospital of Tübingen on 23.03.2021 to Spiegel Online
EU countries (as well as Norway, Iceland and some other countries), the European Medicines Agency (EMA) is responsible for approving covid-19 vaccines, with member state authorities playing a significant role in the approval process. The EMA handles all marketing authorisation procedures for covid 19 vaccines as a matter of priority. In addition, the EMA offers companies the opportunity to submit some chapters of their marketing authorisation application for processing in advance, thus triggering a rolling review while the Phase III trial is still ongoing. Several companies have already taken advantage of this.
In the context of Covid-19 vaccines, the term "herd immunity" keeps coming up. You can find out how this community protection can be achieved and how it helps to contain the spread of a disease HERE
The EMA (like most other regulatory agencies around the world) insists that the efficacy and safety of Covid-19 vaccines be proven in Phase III clinical trials in pandemic areas. A marketing authorization already with the results from phase II trials cannot be considered.
For more information on this topic, see the article "How Covid-19 vaccines are being tested".
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:
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.
Vector virus vaccines: As with mRNA and DNA vaccines, the aim of vector virus vaccines is to induce body cells to produce a SARS-CoV-2 protein by introducing a gene, which then stimulates a defence reaction in the immune system.(2)
. However, the gene in question is introduced into the cells with the help of another, harmless virus. Such harmless viruses, which are suitable as carriers, are called vector viruses. Examples are some adenoviruses from chimpanzees or gorillas and the "Modified vaccinia virus Ankara" (MVA). Vector virus vaccines against Covid-19 from AstraZeneca and Janssen are licensed in the EU. The Russian Gamaleya Institute's Sputnik V vaccine is under rolling review at the EMA. Other vector virus vaccines are in development, such as a vaccine from the German Center for Infection Research (DZIF) and IDT Biologika. Even before the Corona pandemic, there were approved vector virus vaccines against Ebola and dengue.
Vaccineswith inactivated SARS-CoV-2 viruses: Such vaccines are based on one of the oldest principles of vaccine production: In principle, SARS-CoV-2 viruses themselves (produced in cell cultures) are used as vaccines to stimulate a protective immune response. The only difference is that they are damaged beforehand so that they are no longer capable of reproducing. This can be done using a variety of techniques. Like vaccines with viral protein, vaccines with inactivated pathogens are counted among the large group of dead vaccines. One example is the Covid-19 vaccine VLA2001 from Valneva, for which positive results from a phase III trial are available; an EU application for approval is planned.
Peptide vaccines: Such vaccines are similar to vaccines containing viral protein - for example, they contain no genetic material but an adjuvant. But instead of whole proteins, they contain only small fragments of them. These are particularly good at stimulating a protective defence response by T cells (a particular type of immune cell) after vaccination. This is of importance for people who, due to cancer chemotherapy or a congenital immune defect, are unable to produce antibodies well and therefore rely on their T-cells for a viral defence. No such vaccine has been approved yet, but the University of Tübingen (CoVac-1) and the Berlin-based company Belyntic, among others, are working on it.
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 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. A phase II trial has started.
- Orally, with tablets, the DNA vaccine bacTRL-Spike from the Canadian company Symvivo is also to be used. A phase I trial is currently underway.
- The University of Würzburg is developing a live oral vaccine, Aeterna Zentaris, based on an oral typhoid vaccine.
- Argentina's National Scientific and Technical Research Councel (CONICET) is also working on an oral dead vaccine.
The Coalition for Epidemic Preparedness Innovations (CEPI).
CEPI, the Coalition for Epidemic Preparedness Innovations, is a Product Development Partnership (3)
The project is funded by Norway, Germany (Federal Ministry of Education and Research), Japan, Canada, Australia, the Bill & Melinda Gates Foundation and the Wellcome Trust, among others. It was established in 2017 specifically to coordinate, drive and financially support vaccine projects against major epidemics or pandemics.
CEPI has been a key supporter of many Covid-19 vaccine projects, and has also arranged for early ordering of swipe bottles for filling of finished vaccines.
(1) They are projects of the following companies and institutes:
- the start-up Prime Vector Technologies (PVT) (Tübingen)
- the start-up company baseclick (Neuried near Munich) - RNA vaccine
- the start-up Belyntic (Berlin) in cooperation with a university - peptide vaccine
- the University of Würzburg in cooperation with Aeterna Zentaris - oral vaccination based on live oral typhoid vaccine
- the Paul-Ehrlich-Institute (Langen) with the University of Munich - vaccination with vector virus VSV containing gene for an artificial antigen composed of a part of the spike protein (RBD) and a membrane anchorage
- the German Centre for Infection Research / Hannover Medical School / IDT Biologika, which is working on a nasal spray vaccine
- the Viennese company Viravaxx
- the Viennese incubator company Cebina with the University of Pécs (Hungary)
- the US company Sorrento Therapeutics
- the Israeli Tel Aviv University (RNA vaccine)
- the companies Dyadic and Epygen (USA and India) (subunit vaccine)
- CureVac and GSK, which are jointly developing a next-generation Covid 19 vaccine
(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.