How to Make a Vaccine An Essential Guide for COVID-19 & Beyond

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 2001-2007. His narrative approach of choice is to tell the story of viruses, immunology, and vaccines through the history of scientific discovery.

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.

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, caused by a botched batch of polio vaccines. The only question I felt Rhodes could have 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. A range of technical advances and the fact that, during a pandemic, you can more quickly gather data on what fraction of vaccinated people still fall ill, i.e. how effective your vaccine is, mean that 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.

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.

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. 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.