How To Make A Vaccine, John Rhodes. Chicago: University of Chicago Press, 2021.

Summary: A concise handbook discussing the science behind vaccine development, including an explanation of the different types of vaccines, including the various COVID-19 vaccine candidates.

There have been endless polemics for and against vaccines, especially in the years of COVID-19. This book is not one of those. Rather, it represents what I believe is good public science–explaining in terms that a thoughtful layperson may grasp the science behind vaccine development, particularly as it bears on the COVID-19 vaccines. John Rhodes is a research scientist from the UK who has held positions at both Cambridge and the NIH as well as working as director of strategy in immunology at GlaxoSmithKline from 2001 to 2007. Writing from outside the U.S. context he takes the reader step by step through the science while not drawing policy or personal conclusions for us, giving us space to step back from the debates and become learners.

He begins by discussing the pathogens vaccines fight, in this case, the coronavirus that causes COVID. In particular, he focuses on the target, ACE2 proteins to which the spikes on the virus affix themselves, and how this target of attack affects the body. Then he discusses the array of cells that make up our immune system including surveillance cells and different kind of B- and T-cells and how they interact both with pathogens and each other, and how the body manufactures cells with the specificity to kill each pathogen. We learn about the thymus, an organ that disappears in adults and its critical role in ramping up our immune system. And Rhodes discusses the crucial role of adjuvants in the vaccine material, chemical or microbial agents delivered with whatever form of vaccine material that helps the body identify it as foreign and intensifies the immune response, enhancing vaccine effectiveness.

Rhodes then turns to vaccines proper, and their discovery through the immunity relatively harmless cowpox confers on those exposed to smallpox. The name vaccine even arises from this, as vacca is the Latin for cow. The basic trick of every vaccine since is triggering the body to produce antibodies against an infection without introducing that infection. Two main ways (until recently) this was done was to either use dead virus or live attenuated virus, as was the case with the polio vaccines that turned summer from “polio season to just “summer.” Eventually additional approaches including viral vectors and various approaches using DNA and RNA material have been developed

Next, Rhodes walks us through the development process and the stages in that process:

1. Exploratory: Studying the virus to determine what components to include to provoke a strong response to the virus without adverse reactions.
2. Preclinical: Conducting tissue and animal studies to study effectiveness with different dosages and adjuvants.
3. Phase I trials: These are human trials with small numbers to study the safety of the vaccine but also whether they provoke an effective response.
4. Phase II trials: These are with larger groups continuing to study safety as well as dosage and adjuvant effects in producing an effective response.
5. Phase III trials: These involve tens of thousands of subjects, continuing to look for even rare adverse reactions. Often these are done in regions with high infections to better establish the real-world effectiveness of the vaccine.
6. Regulatory review and approval. Producers submit an application to certification agencies in each country, such a the FDA in the US. Even after certification, ongoing reporting occurs through the Vaccine Adverse Event Reporting System.

He also discusses long term vaccine research, such as that on DNA and RNA vaccines that have been going on for twenty years, leading to their stunning effectiveness.

There were an unprecedented number of contenders for COVID-19 vaccines, representing the various types of vaccines already discussed: inactivated whole-virus vaccines, protein subunit vaccines (also non-living), live attenuated viruses, non-replicating viral vector vaccines, replicating viral vector vaccines, virus-like particle vaccines, and DNA and RNA vaccines. He describes how each works, the ways they interact with the immune system and where they were being developed. He also takes a chapter to warn us against magic bullets and the importance of therapeutics. The history of COVID since this book was written amply illustrates this point–with new variants that reduce (though not eliminate) vaccine effectiveness on one hand and a growing array of therapeutics.

While there has been much controversy surrounding vaccines, Rhodes focuses on the amazing story of how quickly a myriad of vaccine candidates entered trials and how vaccine campaigns began in many countries within a year of the discovery of the virus. It represented advances not only in the science of vaccine development but also unprecedented collaboration of scientists around the world and the clearing of administrative hurdles without compromising safety protocols.

There will always be the threat of dangerous pathogens and it is right to not count on “magic bullets.” But there is much to rejoice in as one learns about the immune system and the science of vaccines. Very few people die of the horror of tetanus or polio. Small pox only exists in freezers. New vaccines hold the promise of protection against malaria, a perennial killer in tropical climates. The research and collaborative steps taken in developing vaccines in record time that seriously reduced the threat of a pathogen novel to the human species seems to me worthy of celebration rather than opprobrium.

I found myself alternating between wonder and hope as I learned more about the science of vaccines. Perhaps it is time, in the aftermath of the pandemic and when the arguments and polemics have quieted, to learn about our amazing bodies, about the dangers novel pathogens pose, and the progress human ingenuity has made to give us the tools to fend off those dangers. This book is a good place to start.