Member of LPPOM MUI Expert Staff (2020 – 2025)
The Main Researcher in Biotechnology, Agency for the Assessment Institute of Application of Technology (BPPT)
The threat of infectious diseases, epidemics, or pandemics on a local, regional and global scale makes the need for drugs and vaccines constant and increases.
Vaccine production technology has experienced a very significant leap forward. The demand for the 2019 world’s coronavirus (COVID19) vaccine exceeds twice its production capacity per year, prompting all vaccine manufacturers to deploy their full capabilities through various platforms. Knowledge of vaccine platform technology and critical points is essential in producing halal vaccines.
The COVID-19 vaccine needed by the world reaches 11 billion doses, while the world’s production capacity is only 6.2 billion per year. The World Health Organization (WHO) estimates it will take 3 to 3.5 years to complete the vaccination target for 5.5 billion people worldwide. Currently, the world’s vaccine producers seem to be mobilizing all the resources to prepare a COVID-19 vaccine, competing quickly with the spread of the pandemic.
Vaccine Platform Technology
The World Health Organization (WHO) defines vaccine platform technology as a technology for producing vaccines using different virus vectors by combining heterologous genes from other proteins into backbones of identical virus vectors.
Platform technology refers to the technology that serves as the basis for developing various processes, applications, and other technologies. Vaccine platform technology is the technology that underlies the mechanism, method of delivery, or cell line that can be used to develop many vaccines. The European Medicines Agency (EMA 2021) defines vaccine platform technology as a collection of technologies that share a common backbone carrier or modified vector with a different antigen or set of antigens for each vaccine derived from the platform.
This platform technology includes (though not limited to) protein-based platforms (virus-like particles), DNA vaccine platforms, mRNA-based platforms, replicons (self-replicating RNA), and virus and bacterial vector vaccines. In short, vaccine platform technology as new technology allows vaccines to be produced quickly and easily by simply replacing the desired gene or antigen on the existing platform, just as quickly as someone can change a video game or a cassette or DVD player on the machine.
State of The Art Vaccine Platform Technologies
There are currently several vaccine platform technologies available, which state of the art can be divided into:
1. CLASSIC VACCINE PLATFORM
Most vaccines currently used for humans can be divided into virus-based or protein-based vaccines.
a. virus-based vaccines can consist of an inactivated and non-infectious virus (whole inactivated virus). Or a live-attenuated virus. Since completely inactivated viruses do not replicate, adjuvants are needed to stimulate the immune system. Live-attenuated virus vaccines are classically produced by cell culture until they lose their pathogenic properties and cause only mild infection upon injection.
b. Protein-based vaccines may consist of proteins purified from viruses or virus-infected cells, recombinant proteins, or virus-like particles. Virus-like particles consist of virus structural proteins or non-structural proteins that do not contain the genome virus. Protein-based vaccines require additional adjuvants to induce a robust immune response. This classic vaccine platform has contributed significantly to eradicating smallpox and the vaccine to prevent cancer. However, this platform’s limitation is that it cannot produce vaccines quickly during a pandemic. In the case of SARS-CoV-2, a large number of viruses were cultivated under biosafety level 3 (BSL3) conditions. Extensive safety testing is required to ensure directly attenuated viruses are safe and do not quickly revert to wild-type. Multiple recombinant proteins need to be produced simultaneously for virus-like particle vaccines.
2. NEXT GENERATION (NG) VACCINE PLATFORM
The main advantage of next-generation (NG) vaccines is that they can be developed based on sequences of genetic information alone. If a virus protein is reported to be immunogenic and capable of protecting against virus infection, then the gene encoding that protein is sufficient to initiate vaccine development. This condition makes the platform highly adaptable and accelerates vaccine development. The COVID-19 vaccines developed from the NG platform are virus vector vaccines, nucleic acid-based vaccines, and antigen-presenting cells.
a. The virus vector vaccine consists of a recombinant virus (i.e., virus vector) that is attenuated, then inserted the gene encodes the cloned virus antigen protein. There are vector vaccines that can replicate, and some do not. The replicating vector vaccine will infect the cells where the vaccine antigen will be produced. Then the virus vector can repeat and spread to infect new cells, making the vaccine antigen. While vector vaccines that do not replicate will only infect cells and produce vaccine antigens, no new virus particles are formed. Since virus vector vaccines have endogenous antigens, the entire body’s immune response can be stimulated effectively. One of the advantages of this virus vector-based vaccine is that a single dose is sufficient for protection.
b. Nucleic acid-based vaccines can consist of either DNA or mRNA and can be adapted quickly when new viruses emerge. DNA vaccines consist of synthetic DNA constructs that code for vaccine antigens. After being absorbed into the cell, the cell from the DNA construct expresses the vaccine antigen.
c. mRNA-based vaccines work on the same principles as DNA vaccines, except that mRNA is inserted. The mRNA vaccine can produce immunity at lower doses since more vaccine antigens are expressed per cell. However, mRNA is generally not very stable, so it is necessary to add modified nucleosides to prevent degradation. Carrier molecules such as nano-sized lipid particles can be used to facilitate the entry of mRNA into cells.
d. Antigen-presenting cell (APC) is an essential component of the body’s immune system against vaccines. The APC vaccine platform is based on modifying APCs into mock APCs transduced with lentiviruses to mimic APCs, as was the case for COVID-19 effectively.
Advantages of Vaccine Platform Technology amides the occurrence of a pandemic that spreads so fast and globally makes speed very vital in responding to the spread. The rapid spread of the pandemic must be responded to with speed in producing drugs and vaccines. The availability of vaccine platform technology makes vaccine production faster.
For example, the FDA’s COVID-19 vaccine from Pfizer/BioNTech and Moderna using the mRNA vaccine platform received emergency use approval (EUA). Then, the EMA, just 11 months after China, shared the SARS-CoV-2 genome virus in January 2020.
The advantage of the next platform technology is flexibility. The speed of response of vaccine manufacturers has been seen since designing a vaccine that only takes days because the platform technology quickly changes or adapts to changes in the genetic material that becomes its input. This makes it the fastest vaccine ever approved in history.
For example, Moderna and BioNTech, which worked with mRNA vaccines for cancer and influenza and Zika vaccines before the pandemic, could easily use existing platforms to produce COVID-19 vaccines.
They just need to replace the relevant mRNA with the coronavirus, then the platform generates the spike protein of the immunogenic SARS-CoV-2 virus.
Halal Critical Point Vaccine
Production includes the design stage, preparation stage (pre-GMP), production stage, and distribution stage. Vaccine products from the platform technology go through all the same steps, but at great speed, so that within 11 months (in the case of Pfizer / BioNTech and Moderna), they get EUA from the FDA and EMA drug authorities.
Applications for platform technology vaccine product authorization are deemed eligible for reduced data requirements. Dossier A complete is required for the first product from the manufacturer, which is based on a specific platform technology for a particular target species. The dossier is often accompanied by a Platform Technology Master File (PTMF) consisting of all platform-related data of reasonable scientific certainty, which will remain and do not change regardless of the type of antigen/gene added to the platform. A comprehensive review can be carried out from the dossier, including the halal aspect.
The COVID-19 vaccine platform technology includes the stages of virus preparation, virus propagation, virus isolation, downstream processes to purification, and formulations to become ready-to-inject preparations.
Halal certification of vaccine products includes verification of platform technology and production facilities. All raw materials, auxiliary materials, packaging materials, and sanitary materials that come into contact with textiles and/or products at all stages of vaccine platform technology must be verified as halal.
All production facilities that come into contact with materials and products must be guaranteed to be free from unclean/haram materials. If all the criteria can be met according to halal standards, the vaccine product can be declared as pure and halal for use.
* Notes:
• Adjuvants are compounds that amplify and/or modulate the immune response to an antigen.
• A virus vector is a virus carrier
• antigen endogenous is an antigen that is produced in the human body
• Transduction is the transfer system using the help of virus genetic material
• Spike protein is a protein shaped like spikes on the surface of the SARS-CoV virus
• Immunogenic is the ability to elicit an immune response in the host’s body
• The dossier is a collection of documents containing detailed information on a subject
REFERENCES
John Hopkins Center for Health Security. 2019. Vaccine Platforms: State of the Field and Looming Challenges. John Hopkins Bloomberg School of Public Health. Baltimore. 25 pages.
European Medicines Agency. 2021. Concept paper for the development of a guideline on data requirements for vaccine platform technology master files (PTMF). Committee for
Medicinal Products for Veterinary Use (CVMP). European Medicines Agency. Amsterdam. 5 pages.
Van Riel D, de Wit. 2020. Next-generation vaccine platforms for COVID-19. Nature Materials. 19: Aug 2020: 810 – 812.
