Review: How To Make A Vaccine

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.

Review: On Immunity

On Immunity–An Inoculation, Eula Biss. Minneapolis: Graywolf Press, 2014.

Summary: A collection of essays about vaccines, immunity, fears, risks, and related concerns about environmental pollutants and other dangers faced by the human community.

A few caveats at the beginning of this review. One is that this book was published in 2014. So it was not written in the context of our current polemics about vaccines to combat COVID-19. Also, the author is not a scientist but a talented writer who has won a number of literary awards and is currently an Artist in Residence at Northwestern University. She is the daughter of an oncolgist. She is also the mother of a child suffering many allergies.

The essays in this work reflect her background as an academic, writer, child of a doctor, and a mother. It is evident that she extensively researched this work. She explores the history of vaccination from which we learn that the term comes from the Latin name for the cowpox virus, from which the vaccinated developed immunity to smallpox. She explores how the understanding of immunity developed over the years, earlier issues with the safety of vaccination, and contemporary research and reporting systems that confirm the high level of safety and rarity of risks.

She makes an important point that the effectiveness of vaccines isn’t simply for individuals but for the communities within which they live and travel. Vaccines limit or eliminate infections when a large portion of the population is vaccinated. At one point she challenges the flawed reasoning that one doesn’t need to get vaccinated because others are. This only works when very few think that way, and an ethic that you can’t commend universally runs afoul of Kant’s categorical imperative. She observes, “Immunity is a shared space—a garden we tend together.”

But she is also a mom who wants to do the right thing for her child. Her personal concerns lead her to a sympathetic examination of the fears of others, the sources of reports about autism, and various contaminants in vaccines. She both acknowledge the continuing influence of these reports and how extensive research studies have refuted all of them. She explores the question of risk, and how highly unlikely risks, like a rare side effect that may be attributed to a vaccine, and the much more prevalent and often more serious risks of the disease vaccines are meant to prevent. In the end, she comes down on the side of vaccination–but hardly in an unthinking, “sheeple” fashion. She gently challenges being more afraid of inoculation than disease, and the luxury of entertaining fears that most of the world can’t afford.

She considers other chemicals in our environment from triclosan in our liquid soaps to plastics in our foods, drink bottles, and mattresses. She comes to recognize that there is no absolute immunity we can confer on ourselves or our children from all that could render harm. She experiences this herself when she required transfusion after nearly dying from an inverted uterus during childbirth, and has to trust the safety of the blood she is given. She balances this sense of our vulnerability with our amazing immune system, that can handle multiple vaccines at once because it responds to thousands of threats every day. She asks hard questions, reviews research and doesn’t simply accept authority, but also acts on the best evidence of the science.

The book wanders a bit. It is a collection of essays, not strictly a scientific or history piece. But it is also a human piece, rather than a clinical account or research paper. Biss does what we all need to do–listen, ask questions, be the parent, and learn to discern between flawed and reliable information, and make the best decisions one can. In many ways, this may be a helpful read for those with concerns about vaccines. It challenges us to make decisions not from a place of narcissism but enlightened self interest that also considers the common good. It is written from outside the current polemics, but reflects the concerns so many of us have.