Excellent study material for all civil services aspirants - begin learning - Kar ke dikhayenge!
SHARE:
New age of programmed Vaccines
Read more on - Polity | Economy | Schemes | S&T | Environment
- A new story emerged: Over the course of the pandemic a fundamentally new vaccine technology has come into its own. When the first, spectacularly positive results from phase 3 trials of the Pfizer/BioNTech mrna vaccine were released on November 9th 2020, they did not just offer a pandemic exit strategy. They also showed, as did the results of the similar vaccine made by Moderna, that the long process through which science has abstracted biological mechanisms from their fleshy and fibrous substrates has reached a new level. Medicine had begun to look like programming.
- Messy: For a long time vaccine production was an often messy and sometimes disgusting business. The polio vaccine developed by Jonas Salk in the 1950s was made in vats of minced kidneys, a process which required thousands of rhesus monkeys to be farmed and killed. In the 1968 flu pandemic Maurice Hilleman, and American virologist, got through chicken eggs by the tonne as he grew 9m vaccine doses in their yolks in just four months.
- Messier: Though the chicken-egg method is still used for flu vaccines today, later vaccine-makers worked out how to grow soups of individual vaccine producing cells—cell cultures—in vats large enough to supply what was needed to control all sorts of other diseases. Doing so made things safer as well as easier. The polio vaccines made from viruses grown in minced monkey kidneys also contained a somewhat dodgy looking virus, now known as SV-40, that was not detected until it had been injected into tens of millions of people. Had it been carcinogenic—there is no evidence that it was, though some debate on the matter continues—it would have been a disaster to make a nuclear meltdown look small-bore.
- Message being sent: But the manufacturing systems that are being used to make the vaccines against covid-19 currently being administered at a rate of millions per day are something else again. They do not produce weakened versions of the virus being vaccinated against, like those used in flu jabs and later versions of the polio vaccine. They do not even produce specific antigens. Instead they just send a message: the genetic sequence which describes the sars-cov-2 spike protein. When presented as messenger rna, or mrna, this message gets cells to produce the protein just as they would if they were infected by the virus. That gives the immune system a risk-free preview of what infection would look like, allowing it to develop its response ahead of time.
- Two ways to send the message: The new vaccines deliver their message in two different ways. In the Oxford/AstraZeneca, Johnson&Johnson and Sputnik V vaccines it is contained in a protein shell derived from an adenovirus. Cells are engineered to make adenovirus particles which have a dna version of the sequence that describes the spike protein nestled inside them. The particles they produce are then harvested to make vaccine. The adenovirus gets the dna into the vaccinee’s cells; the cells transcribe the dna into mrna which they then use to make spike proteins.
- Harvesting virus from a cell culture is hardly a new form of vaccine-making. But the adenovirus, as used in this system, is not really the vaccine. It is not there to produce an immune response to itself. It is the platform which allows the dna within to get into cells and set about producing antigen there.
- An important part of this is that the message in the dna is independent of the particles into which it is packed and of the cultured cells that do the packing. The same manufacturing infrastructure—the same recipe for growth medium, easily modified versions of the cells, identical protocols—could be used to load a different dna sequence into particles which would look just the same. The system is not an interconnected whole, as biological systems are in nature. It has been rendered modular.
- This modularity is helping vaccine companies produce second-generation jabs that protect against variants of sars-cov-2 with which the first generation may cope poorly (see next chapter). Insert the dna for a version of the spike protein which engenders a better response, reboot the system and off you go. In principle the companies might use the same approach to deliver the dna for a completely different antigen, and thus a vaccine against a completely different disease. It’s very different from making vaccines in the old days. Then every vaccine was a new project with a whole new infrastructure. With these technologies, every new vaccine is the same project.
- Second way: The second of the new technologies, mrna, works on similarly modular lines, but is yet more radical. A dna version of the spike gene is used to make huge amounts of mrna in a cell-free system—a solution that contains an enzyme called rna polymerase, the chemicals that power its work, and the raw components from which rna is made, all of which can be bought off the shelf. The mrna thus produced is then packaged into tiny particles of lipid—the inert material from which the membranes around cells are made. After the original dna has been harvested no cells are involved. It is all a matter of clean, scalable industrial chemistry. This simplicity has allowed the mRNA vaccines to be designed and produced on a massive scale in an incredibly short time. Vaccine companies expect to make 2.6bn doses of mrna vaccine in 2021 using manufacturing techniques proved at scale only last year.
- Innovation pathways: Abstraction, repeatability and modularity open new pathways to innovation. For a sense of how this can prove transformative look to the world of computers. Hardware designers work with specified components which do what they are expected to; they have set rules for putting these components together—rules that allow them to build systems far more complex than would be possible if every detail of how every component worked had to be specified from scratch. And users write software which does not need to depend on the quirks of the hardware which embodies it.
- Time has come: The gurus of “synthetic biology”, a school of thought and practice which seeks to re-engineer living systems in a way that makes them easier to engineer further, have been talking about such approaches for decades. They are also seeing them used in an increasing number of industrial settings. The sudden unleashing of rna as a tool for making vaccines and more looks like a kindred phenomenon.
- Today's story: At the moment it is the adenovirus vaccines, not those based on mRNA, that are being produced at the greatest scale and lower cost, handily outcompeting the older techniques using inactivated SARA-CoV-2 which have been tried in China. With state-of-the-art cell cultures and well established supply chains, AstraZeneca expects 3bn doses of its vaccine to be produced this year. India’s Serum Institute alone plans to make 1bn doses. But cell cultures have economies of scale and require a lot of care and attention, while rna manufacturing is in its infancy.
COMMENTS