A pandemic is probably a good moment to understand how vaccines are developed and how they work. This short and educational primer offers relevant background information on viruses and the immune system, and goes into much more detail on vaccines than other recent introductory books. How to Make a Vaccine is written by immunologist John Rhodes who brings to the table both his background in academic research on vaccines and his experience working for GlaxoSmithKline from 2001 to 2007. His narrative approach of choice is to tell the story of viruses, immunology, and vaccines through the history of scientific discovery.
How to Make a Vaccine: An Essential Guide for COVID-19 & Beyond, written by John Rhodes, published by the University of Chicago Press in March 2021 (paperback, 184 pages)
Some of these historical episodes were by now familiar to me. For example, Charles Maitland’s first variolation experiments on prisoners, Edward Jenner’s use of cowpox vaccine to combat smallpox, and the 1950s race for a polio vaccine between Jonas Salk and Albert Sabin. Or the bizarre history of the 19th-century maritime expeditions to distribute the first vaccines around the world, keeping them alive on the long journeys through a carefully orchestrated living chain of infection. Other episodes were new to me. For example that Jenner was not the first to experiment with cowpox vaccination. How Wendell Stanley first visualized viruses under an electron microscope in 1935, and how June Almeida first visualized coronaviruses in 1968.
The only place where I felt this historical approach broke down a bit was when it came to the immune system, which is a complicated topic. The components of our byzantine immune system were not necessarily discovered in a logical order, and I would have loved some illustrations here. Instead, there is a useful table on page 22 summarising the different B and T-cells and their myriad tasks. Nevertheless, I found Rhodes’s explanations of how the different components of the immune system function the clearest I have come across so far. For example, I keep confusing antibodies and antigens (I know, as a biologist I should be ashamed for having to admit this). However, when Rhodes writes “the fragments of germs (pathogens) […] soon became known as antigens” (p. 16) it finally activated a mnemonic in my head.
“[…] I found Rhodes’s explanations of how the different components of the immune system function the clearest I have come across so far.”
Chapters four and five are, to me, the core of this book and obligatory reading. I found them exceedingly useful. The first explains the six steps in vaccine development: exploratory, preclinical, phase I, II, and III trials, and regulatory review. This strict procedure ensures vaccines are safe. In part, it is a product of past errors, such as the 1955 Cutter Incident when a particular batch of polio vaccines had not been properly prepared. The only question I felt Rhodes could have asked and answered more explicitly is how COVID-19 vaccines could be developed so quickly. Many people worry that they have been rushed and might not be safe. You have to read between the lines a bit, but the answers are there. For instance, existing vaccine platforms that can quickly be repurposed, technological advances in genetic sequencing and engineering, rapid dissemination of new findings through open publishing platforms and preprint servers, and financial investment such as Operation Warp Speed in the US. Importantly, a large fraction of your population is exposed to the disease during a pandemic, which allows you to rapidly see what fraction of vaccinated people still fall ill, i.e. how effective your vaccine is. Normally, gathering enough data to draw statistically robust conclusions takes a long time, and an epidemic might burn itself out before you get a chance to do so. As a result of all this, there were 232 (!) candidate vaccines when this book went to print.
The second chapter walks you through the six established types of vaccines. All vaccines rely on exposing your immune system to an antigen to activate an immune response, but there are different approaches. Rhodes provides much more detail and for each type also gives examples of COVID-19 vaccines that are being developed. But, briefly, one way of categorising them is the non-living versus living vaccines. The former use dead viruses, parts of viruses (protein subunits), or virus-like particles, but typically need an additive, a so-called adjuvant, to elicit a sufficiently strong immune response. The latter are more potent and rely on living but weakened viruses or use a replicating or non-replicating carrier, a so-called vector, that is modified to contain fragments of a particular virus.
“Chapters four and five are, to me, the core of this book and obligatory reading. I found them exceedingly useful. The first explains the six steps in vaccine development […] The second chapter walks you through the six established types of vaccines.”
And then there are the new kids on the block, DNA and RNA vaccines, which differ in that they get straight to the heart of the matter. After all, the sole purpose of a virus is to deliver its DNA or RNA to a host cell and commandeer its machinery to produce more viruses. These vaccines achieve the same by directly administering engineered pieces of DNA or RNA that code for viral proteins. As Rhodes highlights, especially RNA vaccines hold great promise as they do not replicate, do not integrate into the host’s DNA, interact directly with the cell’s machinery without intermediate steps, and, like other RNA fragments, after a while are naturally broken down by resident housekeeping enzymes. Both the Pfizer and Moderna vaccines that are currently being rolled out to combat COVID-19 are RNA vaccines.
Finding and testing vaccines are only the first steps to getting a virus under control, so I was very pleased to get an immunologist’s perspective on the additional hurdles. This concerns practical logistical problems such as mass-producing billions of syringes and glass vials, figuring out who should be vaccinated first, and the problem of nations competing rather than collaborating to get their hands on vaccines.
“[…] I was very pleased to get an immunologist’s perspective on the additional hurdles. This concerns practical logistical problems [but] more importantly […]the vexing problem of what he understatedly calls vaccine hesitancy.”
More importantly, however, Rhodes addresses the vexing problem of what he understatedly calls vaccine hesitancy. I found his approach here admirably balanced. He gives the background to a few infamous vaccine scare stories (e.g. the Wakefield affair) while explaining some of the actual problems that can sometimes arise, and how lessons have been learned from this to design safer vaccines. Nor does he trivialize the anti-vaccination movement entirely: “Is it right to attribute all issues of vaccine refusal to superstitions, conspiracy theories, and irrationality? Of course not.” (p. 114), while highlighting more subtle reasons. At the same time, he makes the sharp observation that we need to rebalance “perceptions of individual liberty versus collective responsibility and the good of the community” (p. 116). This, I would add, is true of several other public health measures over which some vocal minority groups have been making a right kerfuffle.
How to Make a Vaccine joins several recent pocket-sized paperbacks that offer brief overviews, whether it is of viruses in general, SARS-CoV-2 in particular, or the botched response of governments. It is an especially nice complement to Chakraborty’s and Shaw’s Viruses, Pandemics, and Immunity that focused more on the immune system and only briefly covered vaccines. Helpfully, the further reading section at the back breaks down references per chapter into general and technical literature.
At a time when online searches for books on vaccines are more likely to turn up misinformation than reliable literature, How to Make a Vaccine is a required primer that demystifies concepts and gives an informative overview of how vaccines are developed and how they work. An essential guide indeed.
Disclosure: The publisher provided a review copy of this book. The opinion expressed here is my own, however.
Other recommended books mentioned in this review:
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Last year August, science writer Ed Yong put it very nicely: “you see, the immune system is very complicated“. Yet, understanding it is important to understanding how the COVID-19 pandemic might evolve, why we are faced with certain public health measures, and how we can hope to combat the pandemic with tests and vaccines. In this brief book, physics and chemistry professor Arup K. Chakraborty and immunologist Andrey S. Shaw offer a general introduction to how our immune system reacts to viruses, and how our medical inventions help out.
Viruses, Pandemics, and Immunity, written by Arup P. Chakraborty and Andrey S. Shaw, published by MIT Press in February 2021 (paperback, 206 pages)
I was particularly looking forward to this book. Amidst the growing crop of books on COVID-19, the immunological details have been somewhat neglected. Kucharski’s The Rules of Contagion looked at the epidemiology of disease outbreaks but was written just before the pandemic materialised (the paperback addresses this to some extent), while Rabadan’s Understanding Coronavirus does what it says on the tin, focusing on the virus, SARS-CoV-2, and the disease, COVID-19.
Viruses, Pandemics, and Immunity is nicely balanced in the way it treats all the relevant elements to understand this topic. You get two chapters with history, introducing you to early procedures and to important scientists such as Edward Jenner, Robert Koch, and Louis Pasteur. By the end of it, you will understand the difference between variolation and the vaccine methods of respectively Jenner and Pasteur. This is followed by three chapters with the scientific nuts and bolts, looking at viruses, the immune system, and epidemiology, and two final chapters looking at the medical countermeasures of antiviral therapies and vaccines. In all of these chapters, details and findings on SARS-CoV-2 and COVID-19 are highlighted.
“Viruses, Pandemics, and Immunity is nicely balanced in the way it treats all the relevant elements to understand this topic, [highlighting] details and findings on SARS-CoV-2 and COVID-19.”
I admit that I found the middle three chapters a bit hit and miss. The one on viruses is, I think, great, explaining how viruses work by taking over the host cell’s replication machinery, how DNA and RNA viruses differ, why COVID-19 went global while SARS and MERS—also caused by coronaviruses—did not, and how SARS-CoV-2 differs from other RNA viruses that we understand better, such as influenza and HIV.
In light of what I said earlier about the immune system, it is not surprising that the chapter on immunity is the longest. It introduces the two components of our immune system, innate and adaptive, and how both function when the body detects an intruder. The innate immune system is, relatively speaking, the simpler of the two, responding to infection immediately by recognizing general characteristics of bacteria, viruses, and fungi. The authors can describe this in five pages, including details on Toll-like receptors and cytokines. The adaptive immune system needs more time to gear up, 5–10 days in humans, and is the more complex of the two. In some 20 pages, the authors here introduce the byzantine arrangement of B lymphocytes that combat viruses directly, and T lymphocytes that destroy infected cells in the body, as well as the memory cells that both types contribute. But rather than discuss the innate and adaptive immune system in the order in which they get activated, the authors discuss them in reverse order, which I found a bit counterintuitive. Given the complicated nature of the beast, the level of detail might challenge readers not well-versed in biology, though a helpful “putting it all together” section runs you through it all again at the end of the chapter.
“Given the complicated nature of the [immune system], the level of detail might challenge readers not well-versed in biology, though a helpful “putting it all together” section runs you through it all again […]”
Similarly, the chapter on epidemiology explains the relevant concepts: the basic reproductive number R0, epidemiological models, the effects of public health measures (“flattening the curve”), and herd immunity. The authors also highlight why different countries have been less or more successful in addressing the pandemic, something that will be explored in-depth in Fighting the First Wave. But here, too, the writing sometimes gets a bit complex. The authors spend three pages on a convoluted explanation with numerical examples to tell you that the more infectious a virus is, the higher the fraction of your population that needs to be immune before herd immunity kicks in. Furthermore, they exclusively discuss social distancing and different strategies to achieve herd immunity, from intermittent lockdowns to simply “weathering the storm”. But the two other pillars of public health measures, hand washing and face masks, are not even mentioned, even though they make important contributions to reducing R0.
The last two chapters are spot on again, focusing on the two main weapons in our medical arsenal. Antiviral therapies block one or more steps (entry, replication, assembly, and release) in the viral lifecycle and there is a brief discussion of existing antiviral therapies such as remdesivir and dexamethasone that have been repurposed for use against SARS-CoV-2. Vaccines, then, stimulate our immune system and this is where the immunological details come in again. How to Make a Vaccine covers all these topics in more detail, but there is a good introduction here to the different types of vaccines, clinical trials, and vaccine development, as well as the logistical challenges of the currently required large-scale production and a brief note on why vaccines are safe and certainly preferable over the alternative. Unavoidably, when discussing promising vaccine candidates against COVID-19, some information is already dated. The Moderna vaccine was undergoing trials when this book was written, while the AstraZeneca and Pfizer ones were in the developmental stages. All three are now being rolled out.
“[…] the book is livened up with cartoony illustrations [though] the decision to not include figure captions limits their utility.”
Throughout, the book is livened up with cartoony illustrations by Philip J. Stork, a senior scientist at Oregon Health & Science University. However, the decision to not include figure captions limits their utility in my opinion. Despite annotations in the figures, some are quite cryptic by themselves. Captions could have formed the perfect bridge and condensed the sometimes complex details found in the body of the text.
Viruses, Pandemics, and Immunity bundles introductions to a number of relevant topics, effectively replacing the need to e.g. get several Very Short Introductions. By highlighting what we know about COVID-19 and SARS-CoV-2 for each of these topics, this welcome book plugs a gap, especially where the immune system is concerned. General readers will want to heed Yong’s warning though, because, you see, the immune system is very complicated.
Disclosure: The publisher provided a review copy of this book. The opinion expressed here is my own, however.
Other recommended books mentioned in this review:
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