< General Studies Home Page 

Content

• Introduction
• During COVID-19 various vaccines

---

Introduction

Live Attenuated virus vaccines such as the combined rubella-mumps-measles vaccines and the yellow fever virus vaccine, induce robust and long-lived antibody and T-cell mediated immunity.

• Note: For the development of yellow fever vaccine, Max Theiler was awarded the Nobel Prize in Physiology or Medicine in 1951.
• These vaccines induce effective but transient immune responses, requiring repeated boosting.
• COVID-19 vaccine developed using this mechanism – Covaxin developed by Bharat biotech.

Viral Vector Vaccines: It uses a safe virus (not harmful) which serves as a platform to produce target proteins to generate immune response.

• Such viral vector efficiently enters cells where the encoded antigen are produced by the bodies protein synthesis machinery.
  • The first example of a licensed viral vector vaccine was the Vesicular stomatitis virus – based vaccine against Ebola, approved in 2019, which was soon followed by an adenovirus-based Ebola vaccine

During COVID-19 various vaccines

• Oxford-AstraZeneca (ChAdOx1 nCoV-19) used adenovirus route.
  • Covishield used in India is a version of this.
• Sputnik V Vaccine also has gone adenovirus route.

Both the above methods (live attenuated virus or viral vector vaccine) used cell culture-based manufacturing facilities which is resource intensive. Further they may also introduce diseases and is safer and stable than vaccine containing whole pathogens.

Therefore, researchers have focused upon sub-unit vaccines that circumvent the need of large-scale cell cultures by delivering nucleic acid (DNA or mRNA) directly to vaccine recipients, exploiting the body’s own capacity to produce proteins.

Subunit Vaccines: (Protein subunit vaccines)

• Protein subunit vaccines include only the parts of virus that best stimulate immune system. These vaccines contain single protein components of the respective virus and are referred as
  subunit vaccine.
• It includes Hepatitis B Vaccine (HBV) and Human papillomavirus (HPV) vaccine.

Advantages:

• No risk of introducing the disease and is safer and stable than vaccine containing whole pathogens.
• Suitable for immunocompromised individuals.
• Well established tech

Disadvantage

• Relatively complex to manufacture (compared to other vaccines like RNA vaccines)
• May require multiple doses.

COVID-19 vaccine developed using this method:

• Corbevax is a protein subunit COVID-19 vaccine developed by Texas Children hospital. It delivers spike protein to the body directly.
  • How was protein manufactured?
    • Add gene of spike protein into yeast to produce large number of proteins.  After isolating the virus spike protein from the yeast and adding an adjuvant, which helps trigger an immune response, the vaccine was ready.
• DNA and RNA subunit vaccines:
  • Advantages of subunit vaccines (DNA or mRNA vaccines)
    • Less Resource intensive and thus easy to manufacture.
    • More flexibility – Since the sequence can be easily changed to encode different antigens.
    • This also makes iterative testing of new candidate vaccines and generation of updated vaccines rapid and efficient.
  • Initially DNA vaccine was thought to be more promising but didn’t translate into success. A likely reason for it was that injected DNA must cross two barriers, the plasma membrane and the nuclear membrane, to reach the cellular compartment where transcription takes place (DNA conversion to mRNA). In contrast, mRNA-based vaccines only need to gain access to the cell cytoplasm where translation takes place (mRNA conversion to protein)
  • Another advantage of mRNA vaccine: Delivered nucleic acid can’t integrate into the host genome. This is an additional safety aspect of this method.
    • E.g of DNA vaccine (developed for COVID-19):
    • E.g for mRNA vaccine (developed for COVID-19): Moderna COVID-19 (mRNA-1273) vaccine.