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COLUMNS
COVID-19 Vaccine Platforms
The Top 5 and How They Work

Crippling healthcare systems, high unemployment rates, and a pile of societal issues, these account for only a portion of the damage done since the start of the COVID-19 pandemic in early 2020. Only time will tell which candidate vaccine will pull us out of the woods as research institutes and biotech companies race to develop a viable vaccine against the novel disease.

By 26 August 2020, the total number of confirmed COVID-19 cases across the globe has reached a staggering 23.8 million. This number is expected to rise as countries start to face second and third waves of the virus amid easing lockdown restrictions.

Conventionally, the development of a vaccine would take between 15 to even more than 20 years. Formulating a vaccine would involve stages of testing and quality control. The development cycle of a vaccine would typically encompass the following stages: exploratory stage, pre-clinical stage, clinical development, regulatory review and approval, manufacturing, and quality control. Clinical development in itself comprises of three separate phases, namely, Phase I (first-in-human study on healthy volunteers), Phase II (safety and efficacy), and Phase III (comparison with standard-of-care or placebo).

Severity of the COVID-19 global pandemic has pushed for rapid development of a vaccine against its coronavirus, SARS-CoV-2. Striving for vaccine development timelines to be compressed into as short as within one to two years has become a global effort. The race for a vaccine against COVID-19 is accelerated by the hope of achieving herd immunity in order to reduce the continued pandemic spread. Vaccines after administration will help to stimulate the human body’s immune system to produce antibodies against the virus or bacteria the vaccine was made for.

With the many types of vaccine platforms available and tested for use in other viable vaccines against a bevy of diseases, here we outline the top 5 vaccine platforms currently being tested as possible COVID-19 vaccines, the mechanisms behind it, and some of the vaccine developers in Asia.

Top 5 Vaccine Platforms

1. Protein-based Subunit

What is it? Protein-based subunit vaccines are just one type of subunit vaccines. These subunit vaccines come in two other forms, polysaccharide, and conjugate subunit. They do not contain live components of the pathogen but only various protein subunits of a microorganism. Such vaccines are usually developed based on formulated peptides or recombinant proteins.

How does it work? Protein-based subunit vaccines contain the antigenic portions of the pathogen – the parts necessary to elicit a protective immune response. Unlike other types of vaccines that may contain inactivated or live-attenuated virus this type of vaccine platform is made up of the main antigenic components of the virus. This will help remove the risk of causing an infection due to the live components. The elicited immune response will help trigger the production of neutralizing antibodies by the body’s immune system against the pathogen. Some potential targets of the virus that could be used for development of protein-based subunit vaccines are, the S (spike) protein and its subunits, as well as the receptor binding domain (RBD) of the S protein.

Hepatitis B vaccines are a well-known protein-based vaccine which comprises of the hepatitis B virus surface antigen.

Who are developing it? Mynvax, Chulalongkorn University/GPO, Thailand, National National Institute of Infectious Disease, Japan/Shionogi/UMN Pharma, Osaka University/ BIKEN/ National Institutes of Biomedical Innovation, Japan, Innovax/Xiamen University /GSK, Yisheng Biopharma Co., Ltd

2. Non-Replicating Viral Vector

What is it? Non-replicating viral vectors use a different inactivated virus such as adeno-associated viruses, alphaviruses, and herpesvirus as a vector to carry components that express the proteins of SARS-CoV-2 virus.

How does it work? Viral vectors used in this form of vaccine usually are able to target immune cells such as dendritic cells to trigger an immunogenic response against SARS-CoV-2 virus. This vaccine platform uses an attenuated viral vector so it will not be able to infect the human body to cause disease. The vector will carry expressed parts of the SARS-CoV-2 virus to elicit an immune response against the novel coronavirus. Since the vectors are not live viruses and have been modified, they will not be able to replicate within the human body.

Who are developing it? National Center for Genetic Engineering and Biotechnology (BIOTEC) /GPO, Thailand, GeoVax/BravoVax, ID Pharma, CanSino Biologics/ Academy of Military Medical Sciences

3. Replicating Viral Vector

What is it? Similar to non-replicating viral vectors, viral vectors are used to stimulate the innate immune system to produce a response against the SARS-CoV-2 virus. The difference lies in the type of vector used to carry the expressed proteins of the SARS-CoV-2 virus. Viruses that are used for replicating viral vector vaccines include, measles virus and vesicular stomatitis virus (VSV).

How does it work? Viral vectors used in this vaccine platform are manipulated to replicate but not at its full capacity or have the ability of cause disease. Expressing protein components of the SARS-CoV-2 virus, the body’s immune system will recognize it and develop immunity against the novel coronavirus. The ability to replicate is also key in this form of vaccine because it would be able to increase the immunogenicity of the candidate vaccine.

Who are developing it? Cadila Healthcare Limited, University of Hong Kong, IAVI/Merck

4. RNA (Ribonucleic acid)

What is it? Ribonucleic acid (RNA) comes in many forms, commonly studied RNA include messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and small nuclear RNA (snRNA). In RNA-based vaccines, a synthetic form of mRNA of the virus is used to induce an immune response through transport by a lipid nanoparticle.

How does it work? The mRNA sequence in the vaccine will code for antigens or proteins similar to those of the SARS-CoV-2 virus. Once administered to the human body, the sequence is translated in host cells to produce the viral antigens. These proteins will then trigger the adaptive immune system, allowing an immune response to produce antibodies against SARS-CoV-2.

Who are developing it? Fudan University/ Shanghai Jiao Tong University/RNACure Biopharma, University of Tokyo/ Daiichi-Sankyo, China CDC/Tongji University/Stermina, CanSino Biologics/Precision NanoSystems, Chula Vaccine Research Center/University of Pennsylvania, Fosun Pharma, Arcturus Therapeutics/ Duke-NUS Medical School

5. DNA (Deoxyribonucleic acid)

What is it? DNA-based vaccines are plasmids containing the DNA sequence which encode the antigens of the virus that will elicit an immune response after delivery into the human body.

How does it work? DNA-containing plasmids in the vaccine are administered into the human body. Some prominent advantages of this vaccine are the ability to stimulate both B- and T-cell responses, vaccine stability, the absence of any infectious agent, as well as the scalability of production.

Who are developing it? Chula Vaccine Research Center, BioNet Asia, AnGes/ Osaka University/ Takara Bio

Besides the top 5 vaccine platforms, other potential vaccine platforms currently tested for a possible COVID-19 vaccine include, inactivated virus, live attenuated virus, replicating bacteria vector, and virus-like particle (VLP).

Based on a recent update by the World Health Organization on the 25 August 2020, there are currently 31 candidate vaccines under clinical evaluation. At this point there are only two COVID-19 vaccines approved for early use with a third one on its way. The first was an adenovirus-based vaccine developed by CanSino Biologics on the 25 June 2020 and the second was a vaccine called “Gam-Covid-Vac Lyo” developed by the Gamaleya Research Institute, part of Russia’s Ministry of Health, approved in August 2020. Announced on 26 August 2020, Russia is looking to approve its second vaccine against COVID-19 in late September to early October. COVID-19 mRNA vaccine being developed by Moderna Therapeutics is also on track to be ready by end of 2020 with promising results seen in its current stage of human trials.

Note from Editor: The COVID-19 situation is rapidly evolving day by day. This article serves to be collated information on the types of vaccine platforms currently being tested. For updated information and full details on COVID-19, refer to the World Health Organization (WHO) website.

References:

  1. Wang N, Shang J, Jiang S, Du L. Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses. Front Microbiol. 2020;11:298. Published 2020 Feb 28. doi:10.3389/fmicb.2020.00298

  2. Robert-Guroff M. Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol. 2007;18(6):546-556. doi:10.1016/j.copbio.2007.10.010

  3. O’Callaghan KP, Blatz AM, Offit PA. Developing a SARS-CoV-2 Vaccine at Warp Speed. JAMA. 2020;324(5):437–438. doi:10.1001/jama.2020.12190

  4. Centers for Disease Control and Prevention, Vaccine Testing and the Approval Process. (n.d.) Retrieved from: https://www.cdc.gov/vaccines/basics/test-approve.html

  5. Channel News Asia, Moderna COVID-19 vaccine appears to work as well in older adults in early study. (August 27, 2020). Retrieved from: https://www.channelnewsasia.com/news/world/moderna-covid-19-vaccine-appears-to-work-as-well-in-older-adults-13056828

  6. Channel News Asia, Moderna COVID-19 vaccine could be ready for use by end of year, US says. (July 26, 2020) Retrieved from: https://www.channelnewsasia.com/news/world/moderna-covid-19-vaccine-ready-use-us-12967246

  7. The Straits Times, Russia readies for approval of second Covid-19 vaccine: Official. (August 27, 2020) Retrieved from: https://www.straitstimes.com/world/europe/russia-starts-trials-of-approved-covid-19-vaccine-on-40000-people

 

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