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When the Plague reached ancient Rome (483 BCE), it was observed that those who recovered were never affected twice and could look after the sick without fear for their own safety. This process is called immunity. Long before anyone understood why or how it worked, the Chinese practiced variolation in which material from pustules of a person with smallpox was scratched into the skin of those who had not had the disease. In the 18th century, Jenner observed that milkmaids were immune from smallpox. Inoculation of fluid obtained from cowpox lesions on a milkmaid’s hands induced immunity to smallpox. (Hence the term vaccine from the Latin vacca, a cow). In the 19th century, Pasteur used weakened forms of germs, such as anthrax, as vaccines. The fundamental idea of a vaccine is deliberate exposure to a relatively harmless or dead version of a germ. The immune system will then recognise and eliminate that germ rapidly if it is encountered again.Getting to know the enemycenter1087120The Covid-19 germ is a virus, so small it can only be visualised using a powerful (electron) microscope. Its diameter is 120nm, about 700 times smaller than the diameter of a human hair. It is a new virus as far as humans are concerned, related to but different from many ‘common cold’ viruses and the so-called SARS virus that almost caused a pandemic several years ago (2003). Its surface is studded with ‘spikes’. These structures allow the virus to attach and penetrate human cells in the airways (nose, throat and all the way down to the air sacs of the lungs). Once the virus gets into a cell, the genetic information within the virus particle. called RNA, instructs the human cell to make many copies of the virus. (I’ll explain about DNA and RNA in a future blog). These newly formed viruses spread to other cells and the outcome can lead to extensive, sometimes overwhelming infection. One of the most challenging facts is that most do not have serious illness, sometimes no illness at all.Although the virus needs animal cells (human or other kinds) to thrive, it can remain infectious on non-living materials such as clothing, food, counter tops, mobile phones or cutlery for hours to days, although this is not the main way that the virus spreads. Spread of the virus between humans mainly occurs in droplets that are transferred by coughing, sneezing or intimate physical contact. Prospects for a vaccineMost of the different kinds of Covid-19 vaccine that are being developed (worldwide, there are at least 80 projects in progress) are based on using the spike component of the virus to induce immunity. It is the spike that allows the virus to attach to human cells. When injected into humans, this ‘dead’ component of the virus will stimulate the human immune system to make antibodies. These antibodies bind to the spikes on the viral surface. This interaction of the spike and the antibody halts the progression of the virus, for example by blocking its attachment to human cells. (Note: This is only one example of how the vaccine can work; it is much more complicated). Don’t shoot the messenger: hear him out.On April 18th, the WHO issued a statement that there is at present no compelling evidence that natural infection with Covid-19 virus induces immunity. In other words, people who become ill with the virus and get better may not be protected if they encounter it again. This should not be confused with situations in which the virus stays dormant and then re-emerges. So, if it is true that natural infection does not result in protection – a huge if – is it reasonable to expect a vaccine to work? After all, a vaccine uses a piece of the virus to induce protection. So, if infection with the natural virus is not effective, the rationale of the vaccine is challenged; that’s the bad news. On the optimistic side, there are many instances in which vaccines outperform natural infection in inducing immunity. One well-known example is with tetanus or lock jaw. Getting this through stepping on a dirty nail does not result in protection. This is because the amount of bacterial toxin that enters the body is so small that immunity does not result. However, the vaccine - consisting of a much larger amount of the toxin in an inactivated and safe form - confers long-lived (many years) protection. Another example is through using what are called adjuvants. These are substances given with the vaccine that boost protective immunity. Before discussing the way forward, here are just a few of the problems that need to be overcome if there is to be an effective Covid-19 vaccine. Without being the messenger of doom and gloom, it’s important to understand the challenges.The vaccine must induce antibodies that protect; binding to the surface of the virus alone is not sufficient. Indeed, some antibodies may be harmful because they help, rather than hinder, the virus to infect human cells – a phenomenon known as enhancement. (If this proves to be a problem, I’ll return to it in a later blog). There is natural variation in the spike structure of Covid-19. The virus could change so that the vaccine no longer matches new variants of the virus. Right now, we do not know enough about the natural variation of the spike of Covid-19, but previous experience with other coronaviruses suggests that this may not be a problem. This is a problem that needs to be revisited as we learn more.Humans are all different. Our genes vary, including those that determine our immune responses. So, the vaccine could work well in some but fail in others. Genetic differences between people may explain, in part, the variations in severity of Covid-19 infection)In the next blog, I’ll address discuss some of the practical problems that are going to be important as vaccine testing begins in humans. Oxford scientists hope to immunise the first volunteers next week.All comments and questions are welcomed. Copyright Richard Moxon. 18.04.2020 ................
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