Technology platforms for COVID-19 vaccines
Global vaccine development
The global vaccine development effort in response to the COVID-19 pandemic has been unprecedented in terms of scale and speed.
Vaccine development has historically been a lengthy and expensive process. Due to these high costs and failure rates, development typically follows a linear sequence of phases, with multiple pauses built in for data analyses, safety profile assessment, and manufacturing decisions.,,
The expedited vaccine development timeline resulting from the global effort in response to the COVID-19 pandemic has been unprecedented in terms of scale and speed, and it represents a fundamental change from the traditional vaccine development paradigm.,,–Four main factors have driven the shortened development time: knowledge, preparedness, investment, and expedited review.
- There was existing knowledge about coronaviruses from work on SARS and MERS. The scientific community worked quickly to identify SARS-CoV-2, and international collaborations have encouraged data sharing.
- A joint EMA/FDA pandemic preparedness working group was set up in 2003, which meant major strategies were already in place. There has also been intensive collaboration with other leading global agencies.
- There has been significant financial investment available.
- Regulatory bodies have diverted resources to expedite review processes and reduce timelines for the evaluations and authorization of medicines.,
EUA: Emergency Use Authorization; adapted from Lurie et al. N Engl J Med. 2020.
Platforms for vaccine development
There are multiple platforms currently in use for vaccine development, some of which are actively utilized in the production of licensed vaccines. Other approaches are more novel and have not yet been approved for use but are currently being investigated as part of the global COVID-19 vaccine development response.-
Platforms actively utilized in the production of currently licensed vaccines
- The inactivated pathogen platform uses a whole, dead pathogen as the antigenic stimulus. These are produced by killing the pathogen with chemicals, heat or radiation. Example vaccines include hepatitis A, poliovirus, and rabies.,
- The live-attenuated pathogen platform, which utilizes a chemically weakened version of the whole pathogen. Example vaccines: rotavirus, yellow fever, varicella-zoster virus (VZV) for chickenpox, and measles, mumps, and rubella viruses (MMR).,
- The protein subunit platform, which takes advantage of conjugating a specific part of an antigenic protein to a polysaccharide to enhance the immune response to the pathogen. Example vaccines: influenza, hepatitis B (HBV), human papillomavirus (HPV),, and VZV for shingles.
- The viral-vectored platform utilizes a chemically weakened or harmless virus as a carrier to deliver DNA encoding antigenic proteins., These types of vaccine have been used since 2010 for Japanese encephalitis, and more recently Dengue disease and Ebola.,,,,
- Viral vector-based vaccines rely on the delivery of one or more antigens encoded in the context of an unrelated, modified virus, and they represent a highly versatile platform that offers many advantages over the more established vaccine technologies.
- This technology either employs live (replicating but often attenuated) or non-replicating vectors.
- When the viral vector vaccines are delivered, antigens are expressed, and the host is able to induce immune responses against the respective target pathogen.
- RNA vaccines use a different approach that takes advantage of the process that cells use to make proteins.,
- Messenger RNA (mRNA) is a natural step in the process of building proteins.,
- An RNA vaccine consists of a mRNA strand that codes for a disease-specific antigen.,
- Once the mRNA strand in the vaccine is inside the body’s cells, the cells use the genetic information to produce the antigen.,
- This antigen is then displayed on the cell surface, where it is recognized by the immune system.,
- The immune response mechanism instigated by mRNA remains to be elucidated.,
Novel vaccine platforms not yet approved for use but currently being explored
- DNA immunization is a novel technique used to efficiently stimulate humoral and cellular immune responses to protein antigens.
- A DNA vaccine is composed of a plasmid DNA that encodes the antigen of interest under the control of a mammalian promoter and can be easily produced in the bacteria.
- Once the plasmid DNA is administered in vivo, the encoded antigen is expressed in the host cells, and then processed and presented by antigen presenting cells such as dendritic cells.
- This most likely occurs in the draining lymph nodes, where both humoral and cellular immune responses are taking place.
- Many DNA vaccines are injected into the muscle but a new method using a ‘gene gun’ is being developed that uses helium to propel DNA into the cells of the skin; If this is successful it will provide a ‘needle free’ vaccine.
Antigenic selection is a crucial element for each of the potential SARS-CoV-2 vaccines, with pros and cons inherent in each platform.
- In the case of the inactivated and live-attenuated vaccines, the use of the whole pathogen/virus provides all the viral proteins, lipids, nucleic acids, etc, for immune stimulation, making them highly immunogenic. However, there is a need to grow a large amount of infectious pathogen, which requires dedicated biosafety-level facilities, and it may be complicated to scale up the manufacturing for mass vaccination programs.,
- When considering other possible candidates for a more focused, rapidly scalable vaccine approach, the spike protein is considered the most promising antigen across the remaining platforms (i.e., protein subunit, viral-vectored, DNA, and mRNA platforms). This protein is on the surface of the virus, stimulates strong immune responses, and mediates entry into the host cell by binding to cell surface proteins (which is essential for maintaining the viral life cycle).,,
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- World Health Organization. Timeline of WHO’s response to COVID-19. https://www.who.int/news-room/detail/29-06-2020-covidtimeline. Updated September 9, 2020. November 27, 2020.
- International Federation of Pharmaceutical Manufacturers & Associations. The complex journey of a vaccine: the steps behind developing a new vaccine. https://www.ifpma.org/wp-content/uploads/2019/07/IFPMA-ComplexJourney-2019_FINAL.pdf. Accessed November 27, 2020.
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