COVID-19 VACCINES

Updated: August 11,2021


The global SARS-CoV-2 pandemic has caused significant loss of life, profound disruption to lives and livelihood, and widespread economic, sociological and psychological damage. Severe COVID-19 involving acute respiratory distress syndrome, multiorgan failure and death remains the most serious threat. Long term sequelae from mild disease has also been reported. The high transmissibility, presence of asymptomatic carriers and emergence of new variants have had a prolonged effect on the global population for the past year. Vaccination constitutes the most promising path back to normal life.

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Vaccines are the key component in the fight against this deadly virus which has taken the lives of more than 4.26 millions people around the world. As of August 2021. Over 4.31 billions doses of vaccine have been administered worldwide.

COVID-19 vaccines

Since the identification of SARS-CoV-2 virus more than 300 vaccines projects started. More than 90 are undergoing clinical evaluation, almost eleven of them approved as far as August, 2021 for emergency use globally. WHO’s Emergency Use Listing (EUL) allows countries to expedite their own regulatory approval to import and administer COVID-19 vaccines. The EUL assesses the quality, safety and efficacy of COVID-19 vaccines.

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SARS-CoV-2 vaccines are targeting the whole SARS CoV-2 molecules or its fragments expressed on its surface by using different technologies . Every vaccine has its peculiarities that makes it unique regarding the efficacy or duration of the induced protection or the safety of vaccine.

Illustration of different platforms employed for making COVID-19 vaccines

Different platforms employed for preparing vaccines. Many are still under development. Here is a brief introduction of how these vaccines works :

1– Whole virus vaccine

  • Vaccines based on attenuated SARS-CoV-2
  • Vaccines based on inactivated SARS-CoV-2

2 – Nucleic Acid Vaccine

  • Naked DNA-based Vaccine
  • mRNA-based Vaccine

3 – Vaccine based on viral vectors

  • Non replicating viral vector vaccine
  • Replicating viral vector vaccine

4 – Proteins and peptides based Vaccine

5 – Other Nanoparticles and virus like particle vaccines

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Vaccine based on attenuated SARS- CoV-2 viruses

The history of vaccine begins with vaccine based on a living microbe, that has been weakened by growing in unfavorable conditions or by generating a genetically weakened version of the virus, so it can not cause disease. Since attenuated virus retain the ability to replicate, they are very effective in stimulating the immune system and inducing a strong and persistent immune memory. This is the most traditional technology. However, the attenuation of trillions of viruses is complex and delicate and can be associated with major biosafety risks especially in immunocompromised. The experience with attenuated virus vaccines shows that rarely attenuated viruses can cause disease, even if this is minor one. Their storage and handling also require carefully monitoring.

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Licensed vaccines of this type already in use, are like Oral Sabin Polio vaccine, Meningococcal vaccine, Pneumococcal vaccine, vaccine for Hepatitis B

Only three projects of attenuated SARS CoV-2 vaccine are in active preclinical development at the following institutions:

  • The serum institute of India, in collaboration with Codagenix, a New York private biotech.
  • Indian immunologist Ltd, in collaboration with Griffith University, Australia.
  • Mehmet Ali Aydinlar University, Turkey

None of these vaccine projects have yet reached the stage of clinical trials.

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Vaccines based on inactivated SARS-CoV-2 viruses

Vaccine based on killed microorganisms belongs to a very traditional technological platform that has led to the development of numerous vaccines. The vaccines produced by this method are more stable than live attenuated vaccines but in order to produce longer duration of memory higher amount or an adjuvant is required.

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While the immunity produced is lesser than that by attenuated virus vaccine, the vaccine is cheaper, easy to handle and much safer. Whole virus Vaccines technology is well established and relatively simple to make. Immunity directed against other surface antigens of SARS-CoV-2 too, not only the spike proteins.

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Other licensed vaccines that use this technology are Hepatitis A Vaccine, Injectable Salk Polio Vaccine, Rabies Vaccine, Influenza Virus Vaccine.

Some of vaccines based on inactivated SARS-CoV-2 virions are:

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  • Corona Vac by Sinovac BioTech, China
  • Sinopharm -BIBB-Cor-v ,Beijing Bio institute of biological Products China
  • Sinopharm – WIBP-Core-v, Wuhan institute of Biological product, China
  • CoviVac. Russia.
  • Covaxin, Bharat Biotech, India
  • Qazvac, RIBSP, Kazakhstan
  • IMBCAMS, institute of medical biology and medical science. China
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Vaccine based on SARS-CoV-2 proteins

This is also a well established technology especially, advantageous for immunocompromised. Initially, these proteins were purified from the microbes while today, in most of the cases they are produced in vitro using the recombinant DNA technology. Relatively complex to manufacture. There are several human vaccines based on proteins present on surface of microbes already in use. Spike proteins in its trimeric form or component of it such as RBD region are the targets of all these coronavirus vaccines. Adjuvant is combined to increase immune response either bacterial origin or synthetic. There are numerous vaccine projects based on SARS-CoV-2 proteins. Vaccines projects using this technology are:

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  • Spike protein or its fragments plus adjuvant-Adimmune, Taiwan; Bektop, Russia; The University of Queensland Australia; Univ Tubingen, Germany
  • Novavax. US
  • EpiVacCorona, by Vector State Research Centre of Virology and Biotech, Russia.
  • Covovax. India.
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  • Protein carried by nanoparticles. Novavax, US, Australia and South Africa.
  • Microneedle skin patch delivering Spike proteins, University of Queensland, Australia.
  • Oral tab containing spike proteins fragments, Vaxart, US
  • Tabacco plant produced proteins, Kentucky Bio Processing, US.
  • Soberana by BioCubaFarma-cuba.

Naked DNA based Vaccines

The DNA and mRNA based platforms offer great flexibility in terms of manipulation of the coded antigen and great potential for speed. Currently there are no DNA vaccines registered for human use; however, DNA vaccines commonly used in veterinary medicine .These vaccines are stable and can be produced in large amounts in bacteria. Once injected, DNA plasmid enter human cells, and their ability to enter may be enhanced by a very short local electrical pulse (electroporation). Once entered, plasmid DNA induces the cell to produce temporarily the target proteins.

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Six DNA vaccines are entering human trails. All code for spike proteins or its fragments.

1 – Naked DNA plasmids

  • Zydus Cadila , India
  • AnGes, Japan
  • Takis , Italy

2 – Naked DNA plasmids plus electroporation

  • Inovio , US
  • Genexine, Korea
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Messenger RNA based Vaccines

These vaccine were first to be developed and tested on volunteers. A novel technology. Several vaccine projects are using this technology. Unlike DNA, RNA must be transported in various ways to enter the human cell. Once entered, the mRNA vaccine temporarily induces the cell to produce the antigen protein coded by mRNA. In most of these vaccine the mRNA is carried by lipid micro vesicles. The target antigen coded by the mRNA mostly if not only is Spike protein, its variant, or its fragments. These vaccine have to be kept at -30 to -80 °C. Some of the vaccine using mRNA technology are:

1 – Lipid vesicles (liposomes)

  • Pfizer, US -BioNTech, Germany
  • Moderna, US
  • Cure Vac, Germany
  • Abogn, China
  • Urevac

2 – Nanoparticles

Arcturus Therapeutics, Singapore.

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Vaccines based on viral vectors

The DNA coding for the spike proteins can be conveyed into the cells by a viral vectors. By inserting the DNA in a virus, it is possible to exploit the virus’s great ability to infect and deliver the mRNA into the human cells. The virus in which DNA is inserted may lose its ability to replicate. Since a pre-existing immunity against the virus vector may affect vaccine efficacy so primates viruses (from chimpanzees, gorilla…) are often exploited as vectors.

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In other cases DNA inserted into replicating active viruses: as these viruses can propagate to some extent, they may induce a more robust immune response. A well established technology but relatively complex to manufacture.

Other licensed vaccine of this type are like Ebola virus vaccine.

There are numerous vaccine projects based on viral vectors that are already in advanced clinical trials, some are approved for emergency use.

a – Engineered non-replicating virus vector

1-Chimpanzee adenovirus:

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AstraZeneca, University of oxford, Sweden-UK-Italy

2 – Gorilla adenovirus, ReiThera ,Italy

3 -human adenoviruses

  • Johnson and Johnson, USA. (Ad26COV2.S)
  • Sputnik V , The Gamaleya Research Institute, Russia
  • CanSino Biological, China ( Convidicea-Ad5-nCoV)
  • Covishield, India

4 – Adenovirus specifically modified for nasal spray

5- other viruses

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bEngineered replicating virus vectors

1- Intramuscularly (Measles virus, and vesicular stomatitis virus)

2- Influenza virus administered by nasal spray

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A few other technological platforms

  • Symvivo, Canada: orally administered Bifidobacterium probiotics, engineered to carry the DNA encoding the spike protein.
  • Immunomonitor, Canada: heat- inactivated plasma from donors with COVID-19
  • Aivita Biomedical, US: Dendritic cells modified to express SARS-CoV-2 antigens.

List of Approved Vaccines

Image Courtesy of Gulf News
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July 01,2021

reference : An article by Alberto Mantovani -on behalf of the COVID-19 Commission of Academia Nazionale dei Lincei, Rome.

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