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• Various Types of Vaccines

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1) Various Types of Vaccines:

• 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 enter 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.
• Sub-Unit 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 protein was manufactured?
        • Add gene of spike protein into yeast to produce large amount 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 sub-unit 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 for mRNA vaccine (developed for COVID-19): Moderna COVID-19 (mRNA-1273) vaccine.

1) 2023 NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE

• The 2023 Nobel Prize in Physiology or Medicine has been awarded to Katalin Kariko (Hungary) and Drew Weissman (USA) for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccine against COVID-19. Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates contributed to the unprecedented rate of vaccine development duringtheCOVID-19 crisis.
• Background:
  • Other methods of vaccine development – Whole Virus -, protein-, and vector- based vaccines requires large scale cell culture. It is a resource intensive process and limits the possibilities for rapid vaccine production in response to outbreaks and pandemics. mRNA based vaccines solved these problems.
  • During the 1980s, efficient methods of producing mRNA without cell culture were introduced, called in-vitro transcription. Ideas of using mRNA technologies for vaccine and therapeutic purposes also took off, but roadblocks lay ahead.

In vitro transcription

In vitro transcription is a laboratory technique used to synthesize RNA moleculesoutsideofa livingcell. This process involves usinga DNAtemplate and the enzyme RNA polymerase to generate a complementary RNA strand. In vitro transcription is a fundamental tool in molecular biology and biochemistry, and it has various applications, including the production of RNA molecules for research, such as RNA probes, RNA sequencing, and gene expression studies.

• • • In vitro transcribed mRNA was considered unstable and challenging to deliver. It required development of sophisticated carrier lipid systems to encapsulate the mRNA.
    • This mRNA also gave rise to inflammatory reactions.
    • These problems limited the enthusiasm for developing the mRNA technology for clinical purposes.
• Contributions:
  • In 1990s, Kariko was an assistant professor at the University of Pennsylvania and met immunologist Drew Weissman there.
  • They worked together to prevent the immune system from launching an inflammatory reaction against lab-made mRNA, previously seen as a major hurdle against therapeutic use of mRNA.
    • They found that inflammatory response was almost abolished when base modification was included in the mRNA. Therefore, in 2015 they published that adjustments (modifications) to nucleosides, can keep the mRNA under the immune system’s radar.
    • Later, they also showed that the delivery of mRNA generated with base modification markedly increased protein production compared to unmodified mRNA. This effect was due to the reduced activation of an enzyme that  regulates protein production.
• Development of Vaccines:
  • After the above discoveries, interest in mRNA technology picked up.Vaccines for Zika and MERS-CoV were pursued.
  • After the outbreak of COVID-19 pandemic, two base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed at record speed. Protective effects of around 95% were reported, and both vaccines were approved as early as Dec 2020.
  • The impressive flexibility and speed with which mRNA vaccines can be developed pave the way for using the new platform also for vaccine against other infectious diseases.
  • In the future, the technology may also be used to deliver therapeutic proteins and treat some cancer types.
• How mRNA vaccine protects you against COVID-19:

• Through their fundamental discoveries of the importance of base modification in mRNA, this year’s Nobel Laureates critically contributed to this transformative development during one of the biggest health crisis of our time.