COVID-19 vaccine platforms

Vaccines have been in production for hundreds of years and all of the different forms of technology or so called ‘platforms’ have been applied to the worldwide efforts to produce  SARS-CoV-2 or COVID-19 vaccines. No approach is off the table as researchers and pharmaceutical companies combine efforts to limit the pandemic through immunisation. Hence, there are multiple vaccine approaches utilised by the over 250 COVID-19 vaccines currently in development and use, including several newer and novel approaches.

This reference page provides a summary of the approaches and examples of COVID-19 vaccines utilising these different platforms. The majority of the vaccines being developed initially require a two dose course to provide clinical protection against the SARS-CoV-2 virus. There are currently no recommendations for booster doses beyond this, however this may change with further trial data and the emergence of variant strains.

Traditional vaccine approaches

Inactivated virus vaccines

Inactivated vaccines are created by killing or deactivating the virus so that it is unable to replicate. The whole virus or a subunit of the virus can be used. This approach has been used for decades, such as with hepatitis A and inactivated polio vaccines.

These vaccines are generally safer than live-attenuated vaccines as they can be given to everyone, including those with immunocompromise. However, the immune response induced by this mechanism alone may not be as strong or long-lasting and booster doses or an adjuvant may be required (additional vaccine components that boost the immune response).

Another advantage of these vaccines is that they can be stored at standard refrigerator temperatures of +2° to +8°C. As a result, these vaccines are a lot more useful to developing countries which may not be able to store large amounts of vaccines at very low temperatures.

Examples of inactivated COVID-19 virus vaccines being used overseas include two vaccines developed in China; the Sinovac CoronaVac COVID-19 Vaccine and the Sinopharm COVID-19 vaccine BBIBP-CorV.

Protein-based vaccines

Part of the pathogen that induces an immune response is used to make the vaccine; this part may be a whole protein or fragments of the protein. These vaccines are safe, relatively simple to make and are cheaper to produce. However, multiple doses or an adjuvant is often required to induce an adequate immune response. This method is used to make hepatitis B vaccines. The most common component of the SARS-CoV-2 virus used to make these vaccines is the spike protein. Spike proteins play a key role in pathogenesis; allowing entry into human host cells and hence subsequent infection.

One disadvantage of using whole protein vaccines is that they have an unstable structure which may lead to loss of immunogenicity.

Nuvaxovid (Novavax) is one example of a protein-based vaccine which utilises the SARS-CoV-2 spike protein.

Novel vaccine approaches

In the past few decades, vaccine technology has made significant advances particularly in relation to genetic technology. These newer vaccines pave the way for more efficient and timely vaccine production as soon as the genetic sequence of a new pathogen is known.

Nanoparticle-based and virus-like particles vaccines

Nanoparticle-based vaccines have received increasing interest in recent years due to their good safety profile and high immunogenic potential. Nanoparticle vaccines are constructed by attaching selected key components of a pathogen (such as the COVID-19 spike protein or viral DNA) to an engineered nanoparticle (nanocarrier). This nanoparticle is commonly an engineered virus-like particle (a molecule that mimics the virus but is not infectious). These nanoparticles are highly stable and less prone to degradation than traditional protein vaccines. The human papillomavirus (HPV) vaccine is an example of this approach.

Nuvaxovid (Novavax) can also be classified as a nanoparticle vaccine as it utilises a nanoparticle carrier attached to the Sars-CoV-2 spike protein.

Genetic vaccines

Genetic vaccines deliver one or more of the pathogen’s genes to provoke an immune response. There are two types, DNA and messenger RNA (mRNA) vaccines. DNA is the original genetic sequence which codes for all components of the virus. Firstly, DNA is converted into mRNA and then, mRNA is converted into viral proteins. The immune response is triggered by the production of these viral proteins.

Comirnaty (Pfizer) and Spikevax (Moderna) are examples of mRNA vaccines.

These vaccines can be produced faster than traditional vaccines as development can begin as soon as the genetic sequence of a new pathogen is available. Although DNA and mRNA vaccines had never been licensed prior to the COVID-19 pandemic, they were already under development for other viruses, such as influenza. Post-licensure surveillance of Comirnaty and Spikevax have shown them to be safe and effective.

Due to the instability of DNA and mRNA, these vaccines require ultra-cold chain systems  for storage and transport. These conditions make the delivery of these vaccines more complicated as infrastructure is not readily available in all areas. Australia does not currently have the capacity to make mRNA or DNA vaccines locally. However, there are currently multiple mRNA agencies being set up to support mRNA therapeutic developments, including at both a national and jurisdictional level in Victoria and New South Wales. This includes a plan for onshore production of mRNA vaccines to strengthen our capacity against future pandemics and other diseases. This will enable priority access to the Australian population to safe and effective mRNA therapeutics as soon as they become available.

DNA vaccines have historically not worked as well, because it is difficult to get enough DNA introduced to make a strong immune response. As a result, DNA vaccines may need to be delivered differently from routine vaccines. Inovio’s COVID-19 DNA vaccine candidate is administered intradermally by a device that releases a small electric current to allow entry of the vaccine through the skin.

There has been some vaccine hesitancy about potential integration of mRNA vaccines into the host’s (vaccine recipient’s) DNA, although this is not possible. mRNA from a vaccine is only capable of producing proteins and cannot be reversed back into DNA and hence is unable to modify the host DNA. mRNA vaccines have been shown to create a strong immune response, especially compared to DNA vaccines, have the potential for low-cost manufacture and a good safety profile.

Viral vector vaccines

Viral vector vaccines work by using a virus (viral vector), which doesn’t cause disease in humans, to carry part of the pathogen’s DNA into human cells. Some viral vector vaccines enter cells and cause them to make viral proteins (non-replicating viral vectors). Other viral vectors slowly replicate, carrying SARS-CoV-2 proteins on their surface (replicating viral vectors). Replicating viral vectors best mimic natural infection and hence produce a strong immune response and can be used in lower doses.

Human adenoviruses, viruses which cause the common cold, are a commonly used viral vector for COVID-19 vaccine development. Most encode the spike protein. While adenovirus vectors are well tolerated and highly immunogenic in most people, pre-existing immunity to the viral vector may hamper the immune response to the vaccine. Animal adenoviruses can be used to overcome this; this is utilised by Vaxzevria (Astra Zeneca) which is a non-replicating vaccine using a chimpanzee adenovirus vector. The Johnson & Johnson/Janssen COVID-19 vaccine and the Sputnik V (Gamaleya Research Institute) are other examples of non-replicating viral vectored vaccines currently in use internationally.

Other traditional vaccine approaches

Live-attenuated virus vaccines

Live vaccines contain a weakened (attenuated) form of the pathogen that is less capable of replication and is less virulent. Live vaccines induce a strong immune response and provide long-lasting immunity. This method has been used to protect against multiple viruses and is currently used to make the measles, mumps, rubella, chickenpox (varicella) and one rotavirus vaccine. The main disadvantage of this platform is that they cannot be administered to people who are immunocompromised or pregnant. In addition, they take longer and are more difficult to mass produce because these viruses need to be grown under enhanced biosafety protocols in specialised laboratories.

Codagenix and Meissa both have live-attenuated vaccine candidates in phase 1 clinical trials. Both vaccines are administered intranasally.

Resources

• Frontiers in Immunology: Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines
• Milken Institute COVID-19 Tracker
• World Health Organization: Draft landscape of COVID-19 candidate vaccines
• Australian Government Department of Health: Australia’s vaccine agreements
• Children’s Hospital of Philadelphia: Can mRNA vaccines alter a person’s DNA?