Vaccine Platforms 101 for COVID-19
Out of a crowded field of vaccine candidates against COVID-19, a technology from the University of Oxford has recently pulled ahead. It has been proven effective in pre-clincal tests in rhesus monkeys and could be ready for development by the end of the summer. This would be much earlier than the 18-month timeline that was expected for any vaccine to be ready for public use. The reason for the speedy deployment of this particular candidate, if approved, lies in its previous use towards another SARS-related coronavirus called MERS. But whether this technology, called the viral vector method, is the best platform for future vaccine development is yet to be determined.
While effective anti-viral treatment and more ventilators will be necessary to reduce mortality, a vaccine for COVID-19 is essential for return to any version of previous normalcy. Infusions of antibodies derived from the plasma of infected patients was being explored as a way to transfer immunity for a few weeks or months, but this approach would have been an interim solution until a vaccine was found. Vaccines enable our immune system to create its own antibodies and thereby grant long term resistance to a virus. The MMR vaccine for mumps, measles and rubella employs weakened versions of the viruses to achieve this effect but this method requires a longer timeframe in order to culture and modify a novel virus. Instead, newer approaches to vaccine development rely on using portions of the COVID-19 genome sequence to just create copies of its spike protein. Our immune system is then able to identify the virus using the spike protein signature and create antibodies against it. While injecting synthetic protein as a vaccine is a better solution than antibodies derived from plasma, it would require the addition of a chemical agent known as an adjuvant to activate the immune system.
The viral vector method used by the Oxford group takes an existing animal virus which is harmless to humans and edits this genome to include the portion of the COVID-19 sequence that codes for its spike protein. This approach, as well as the DNA vaccine method which uses bacteria plasmids instead of animal viruses as the template for editing, relies on the human cell’s mechanism for translating the plasmid or viral vector into proteins which will be then released from the cell. Both these methods are more effective at activating the immune system (or self-adjuvanting) than the protein vaccine. The disadvantage of the DNA vaccine approach is that plasmids are independent loops of code which do not have a protein shell and would need separate delivery systems such as lipid-based carriers to make them effective. Viral vectors already posses the protein shell from the animal virus but the template virus has been used to launch a particular vaccine cannot be re-used on another strain because your immune system will already have produced antibodies against it. This makes viral vectors a less than ideal platform for repeated vaccine development. A promising alternative was the mRNA-based approach which was seen as a front runner for the COVID-19 vaccine. This technology uses single-stranded mRNA which codes only for the spike protein and are small enough for uptake by the cell even without a protein shell to mediate entry. The human cell then immediately begins to translate the mRNA into protein which essentially achieves the same outcome as the DNA and viral vector vaccines but without their disadvantages.
Still, the viral vector method could produce a vaccine earlier than any other platform because the chimpanzee virus being used as a template by the team at Oxford had already been tested for safety as part of trials for other vaccines including against MERS. This allows for expedited clinical trials and also means that previous research towards scaling up manufacturing of this viral vector could be applied towards the COVID-19 vaccine. Production of doses by September would be best case outcome provided this candidate shows efficacy in preventing infection in humans. However, we will also need technologies like the protein-based, DNA, and mRNA approach to help meet worldwide demand for the COVID-19 vaccine and in order to respond quickly to new viruses that arise in the future.
