I thought a review for the non-expert on how vaccines come into being might be informative (footnote-1). I suspect there might also be some surprises.
Reports in the press are appearing saying we’re on the brink of a coronavirus Vaccine. Is this true? Well, it all depends upon your definition of “brink” but there is reason for optimism. Before I get into the meat of the subject, a quick word on terminology, because I’ve seen the general media getting things a little muddled (footnote-2). Coronaviruses (CoVs) are a group of viruses with a crown-like appearance responsible for outbreaks such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) as well as other respiratory diseases. The coronavirus responsible for the current mayhem is called SARS-CoV-2, and the disease it causes is called Covid-19. Confusing? Sorry I don’t decide on the names. I’ll just say us scientists are a pedantic lot and like hard definitions (for good reason).
Your immune system is amazing. It constantly patrols the body for things it considers shouldn’t be there, including viruses, bacteria, cancer cells and parasites. If it sees something it doesn’t like it produces proteins called antibodies, which remind me of the scene in the Godfather where Michael Corleone hugs his brother marking him out for assassination. Likewise, antibodies hug the invader, marking them out for assassination by other cells of the immune system such as the aptly named killer cells (or white blood cells). This is the simplified version, but there’s a huge complexity to the immune system, a whole host of cells from T and B lymphocytes, to macrophages and neutrophils. Then there’s a protein cascade system called complement which leads to inflammation; a mechanism to localise and inactivate the pathogen.
With all this going on, it begs the question why we get disease at all. The answer is that when the virus invades, it takes over the cells of the body to make more viruses, which then invade other cells in a chain reaction. The immune system fights back, but it’s a race between all the immune factors being able to join the fight versus viral overload. If the immune system wins, you recover, if the virus wins you don’t. Assuming you recover, the immune system holds a grudge and remembers the invader so if it sees it again it’s ready to go. It’s under these conditions we say we have immunity. The problem with SARS-CoV-2 however, is that the immune system hasn’t seen it before and so must start from scratch.
Vaccines are as amazing as your immune system and don’t let Jim Carrey or Jenny McCarthy tell you otherwise. Vaccines are the biggest contributors to public health since germ-theory and have eliminated, or virtually eliminated, several diseases including smallpox, diphtheria and tetanus. I had friends at school with leg-braces due to polio and I’m pleased to see these days behind me. Sadly, through the efforts of some anti-vaxxers (footnote-3) these diseases are now returning. But I digress; let’s get back to vaccine development.
A vaccine is designed to ‘show’ the invader (SARS-CoV-2 in the current case) to the immune system so that the immune system can produce antibodies specific to it. When the real virus arrives as an infection, these antibodies are ready and waiting from the very beginning. Vaccines come in many different forms and new technologies are facilitating fresh approaches to vaccine design. The first vaccines were simple and based on the pathogen itself. By damaging the pathogen (whatever it may be: bacteria/virus/parasite) it can be safely given to humans as a vaccine without making them ill. The immune system has now seen at least part of this pathogen before, and so it can rapidly produce protective antibodies ready to go. Probably, most people think all vaccines are made in this way, but times are changing.
Many of these types of vaccines have been around for some time, but let’s jump to the state-of-the-art in vaccine development – vectored vaccines. DNA has been described as a blueprint for life (I don’t like the term blueprint, but it’ll serve a purpose here). It consists of a series of chemical bases, the sequence of which represents the genetic code of an organism – be it bacteria or humans. Some viruses have DNA and others, such as SARS-CoV-2 have RNA as their genetic material. Like DNA, viral RNA still dictates how all the complex building blocks assemble to make a fully-formed virus. Scientists isolated SARS-CoV-2 RNA very soon after the outbreak, sequenced the chemical bases and broke its genetic code. These data could then be electronically transmitted and shared around the world. All this happened some time before the virus itself was isolated.
With this code, scientists were able to figure out which sequences of bases are likely to be responsible for making the ‘crown-like’ spikes you see in pictures of the coronavirus. It’s through these spike-proteins that SARS-CoV-2 is thought to enter cells and cause disease. Now things get a little complicated. Viruses have a shell which for obvious reasons is called a viral shell. This shell is NOT pathogenic but it can be used as a vector for genetic material from a pathogen such as SARS-CoV-2 which codes for proteins likely to protect someone from infection (we call this ‘immunogenic’). Commonly used viral vectors include adenoviruses and modified Vaccinia Ankara (MVA) virus. Because these viral vectors have been used many times in clinical trials with different inserts from pathogens (eg TB, HIV, Flu), the vector is known to be safe in humans. The addition of genetic material from a new pathogen is unlikely to alter the safety profile of the viral vector.
Let’s be clear what we are talking about here. Scientists are taking a bit of one virus, the vector, adding RNA code from SARS-CoV-2, the sequence of which was probably emailed to them and then synthesised in the laboratory. They are carrying out an amazing feat of molecular engineering, slicing and dicing viruses with the intention of fighting the very diseases that they cause.
Traditional vaccines take over a decade to develop, but vectored vaccines have the potential to cut that to perhaps a year or so. While virally-vectored vaccines may be quicker to develop, they must still go through clinical trials in people to establish safety and efficacy, and that takes time. The trial might show the vaccine is not effective, which is why several different vaccines are in development simultaneously and why international co-operation and collaboration is so vitally important. Moreover, we may worship celebrities but the real heroes, in my option, are those anonymous volunteers who sign up for the clinical trials:
In the case of Covid-19, other types of vaccine are under investigation and will be investigated in clinical trials in parallel. So while a Covid vaccine won’t be available tomorrow, this outbreak has mobilised the international community to share and communicate like never before. This has really highlighted the importance of international collaboration; getting a vaccine against a completely new pathogen into humans for testing in Seattle just four months after identifying the first case in China is a mind-blowing timescale.
Despite these amazing timelines, in order to fully check the vaccine candidates for safety and efficacy the Covid-19 vaccine is likely to be at least a year away – which isn’t really on the brink, but is still so much faster than ever before, and that’s something to celebrate. There’s a good account in the Guardian on this.
I’m not an epidemiologist and so I’m unqualified to comment but here’s a link to a great article in the Washington Post which explains the epidemiology of transmission and why isolation is a good idea. I’ll also give praise to the London School of Hygiene and Tropical Medicine (LSHTM) which is running a free online course starting March 23rd. It’s world-class expert information like this that needs to be disseminated, in my opinion. And it’ll help pass the time while you’re in isolation!
A last word about impaired immune systems and “boosting the immune system”. There are diseases that impair the immune system, and medical treatments such as transplants, after which the immune system is deliberately suppressed to avoid organ rejection. People with impaired immune systems are more at risk of getting a severe response to Covid. There is also a well-document effect called immunosenescence, whereby, with age, the immune system becomes less like a world-class athlete and more like me on my mobility scooter. This is why this population is of concern and why the UK government are talking about isolating over 70-year-olds. I’ll not comment on whether 70-year-olds are likely to comply, that’s a different story. In the meantime, blueberries, vitamin-C and chakra-crystals (or whatever), do not boost your immune system or your bank account. And I say again – vaccines do NOT cause autism and it saddens me that I have to keep saying this. It saddens me even more when the antivaccine lobby spread their conspiracy theories while breath-taking scientific advancement is making real progress against the diseases that affect us all.
Just as I posted, this appeared. It illustrates how fast things are moving.
Footnotes
(1) As Clint Eastward said in Magnum Force, “… a man’s got to know his limitations” and I certainly have limitations when it comes to understanding vaccine development. I therefore reached out and sought expert advice. Huge thanks therefore, to my anonymous contributor.
(2) I corrected the terminology on my previous blog post.
(3) From a comment on my last blog post, yes, I know other cleaning products are available.
Graham Lappin 
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