Vaccine

• 1. Introduction

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  A vaccine is a biological preparation that gives the body active acquired immunity to a particular infectious or malignant disease. It usually contains an agent that resembles a disease-causing microorganism. That agent is often a weakened or killed form of the microbe, one of its toxins, or one of its surface proteins. The immune system learns to treat that agent as a threat. It destroys it, then recognizes and destroys the same microorganisms if they appear again. The World Health Organization reports that licensed vaccines exist for twenty-five different preventable infections. So how did a practice that began with powdered scabs blown up the nose grow into one of the most studied interventions in medicine? And why, despite overwhelming scientific consensus on their safety, does refusal still rank among the WHO's top ten global health threats? The answers run from a milkmaid's hand to lipid nanoparticles.

• 2. A Name From The Cow

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  Variolae vaccinae means smallpox of the cow. Edward Jenner devised the term to denote cowpox, and the words vaccine and vaccination descend directly from it. Jenner both developed the concept of vaccines and created the first one. In 1796 he took pus from the hand of a milkmaid with cowpox and scratched it into the arm of an 8-year-old boy named James Phipps. Six weeks later he variolated the boy with smallpox and observed that he did not catch the disease. In 1798 Jenner used the cowpox phrase in the long title of his Inquiry into the Variolae vaccinae Known as the Cow Pox, describing how cowpox protected against smallpox. That same year he reported the vaccine was safe in children and adults and could be transferred arm-to-arm, which cut reliance on uncertain supplies from infected cows. In 1881, to honor Jenner, Louis Pasteur proposed extending the terms to cover the new protective inoculations then being developed. The science of vaccine development and production now carries its own name, vaccinology.

• 3. Scabs And Royal Courts

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  Powdered smallpox material, usually scabs, was blown up the nostrils in a method of nasal insufflation. According to historian Joseph Needham, Taoists in China practiced a form of inoculation as far back as the 10th century, passed down by oral tradition, though that claim has been criticized because the practice was not written about. The oldest documented use of variolation by the Chinese dates back to the fifteenth century, with various insufflation techniques recorded through the sixteenth and seventeenth centuries. Two reports on the Chinese practice reached the Royal Society in London in 1700, one from Martin Lister via an East India Company employee in China, the other from Clopton Havers. Mary Wortley Montagu, who had witnessed variolation in Turkey, brought the folk practice to Britain in 1721. That year she had her four-year-old daughter variolated before physicians of the Royal Court. Later in 1721 Charles Maitland variolated six prisoners in Newgate Prison in London, a success that drew the royal family into promoting the procedure. Yet the practice carried real danger. In 1783, several days after Prince Octavius of Great Britain was inoculated, he died.

• 4. How Protection Works

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  The immune system recognizes vaccine agents as foreign, destroys them, and remembers them. When the virulent version of an agent is later encountered, the body recognizes the protein coat. It neutralizes the target before it can enter cells, then finds and destroys infected cells before the agent multiplies to vast numbers. Innate immunity may activate in as little as twelve hours, but adaptive immunity can take one to two weeks to fully develop. During that window the host can still become infected. Protection is not always complete. Host-related lack of response occurs in an estimated 2 to 10 percent of individuals, due to factors including genetics, immune status, age, health, and nutritional status. One genetic cause is X-linked agammaglobulinemia, in which the absence of an enzyme essential for B cell development prevents the host from generating antibodies. Older people often respond less than younger people, a pattern known as immunosenescence. Even when immunity is partial or temporary, it can raise the reinfection threshold for a whole population. If a vaccinated person still develops the disease, that breakthrough infection is likely to be less severe and less transmissible than in unvaccinated cases.

• 5. The Measles Ledger

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  In 1958 there were 763,094 cases of measles in the United States, and 552 deaths resulted. After new vaccines were introduced, cases dropped to fewer than 150 per year, with a median of 56. In early 2008 there were 64 suspected cases, fifty-four of them associated with importation from another country, though only thirteen percent were actually acquired outside the United States. Of those 64 individuals, 63 had either never been vaccinated or were uncertain whether they had been. The measles vaccine is estimated to prevent a million deaths every year. When the vast majority of people are vaccinated, an outbreak becomes much harder to start, let alone spread, an effect called herd immunity. Smallpox was eradicated outright, and diseases such as rubella, polio, mumps, chickenpox, and typhoid are nowhere near as common as a century ago. Polio, transmitted only among humans, has been pushed back to endemic status in parts of just three countries, Afghanistan, Nigeria, and Pakistan. The difficulty of reaching all children, cultural misunderstandings, and disinformation have pushed the anticipated eradication date past several deadlines.

• 6. A Catalogue Of Strategies

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  Some vaccines contain live, attenuated microorganisms, cultivated under conditions that disable their virulent properties. Examples include yellow fever, measles, mumps, rubella, and the bacterial disease typhoid. The live tuberculosis vaccine developed by Calmette and Guerin uses a virulently modified strain called BCG rather than a contagious one. These live forms provoke more durable responses but may be unsafe for immunocompromised people and can rarely mutate to a virulent form. Inactivated vaccines use killed organisms, as with IPV polio vaccine, hepatitis A, rabies, and most influenza vaccines. Toxoid vaccines, such as tetanus and diphtheria, are made from inactivated toxic compounds rather than the microorganism itself, and Crotalus atrox toxoid even protects dogs against rattlesnake bites. Subunit vaccines use a fragment of the microbe, as in the hepatitis B vaccine made from the virus surface proteins and the Gardasil HPV vaccine. Conjugate vaccines link a poorly immunogenic polysaccharide coat to proteins, the approach used in the Haemophilus influenzae type B vaccine. Outer membrane vesicle vaccines are best known for serotype B meningococcal disease. Genetic vaccines take in a nucleic acid so cells produce a pathogen protein, a group that includes viral vector, RNA, and DNA vaccines.

• 7. Operation Warp Speed

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  BNT162b2 was an mRNA vaccine developed in 2020 with the help of Operation Warp Speed and deployed at scale against the COVID-19 pandemic. RNA vaccines are composed of the nucleic acid RNA packaged within a vector such as lipid nanoparticles. Among the COVID-19 vaccines, the Pfizer-BioNTech vaccine and the Moderna mRNA vaccine are approved for use in adults and children in the US. In 2021 Katalin Kariko and Drew Weissman received Columbia University's Horwitz Prize for their pioneering research in mRNA vaccine technology. These belong to a third generation that also includes DNA vaccines, which use a plasmid encoding an antigenic protein from the target pathogen. In 2016 a DNA vaccine for the Zika virus began testing at the National Institutes of Health, while Inovio Pharmaceuticals and GeneOne Life Science tested a different Zika DNA vaccine in Miami. When increased production was urgently needed in 2021, the World Trade Organization and governments weighed waiving intellectual property rights and patents on COVID-19 vaccines to remove barriers to timely access. The biggest barrier to production in less developed countries, by the WHO's account, has not been patents but the financial, infrastructure, and workforce requirements for market entry.

• 8. The Cost Of Confidence

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  Building a vaccine production facility can cost anywhere from 50 to 500 million US dollars, requiring highly specialized equipment, clean rooms, and containment rooms. Vaccines are intended for millions of people who are mostly perfectly healthy, which drives a production process far more rigorous than ordinary pharmaceutical manufacturing. Plants may take between 4 and 6 years to construct, and the full process of vaccine development runs between 10 and 15 years. The companies with the highest market share are Merck, Sanofi, GlaxoSmithKline, Pfizer, and Novartis, with 70 percent of vaccine sales concentrated in the EU or US as of 2013. India's Serum Institute is one of the largest producers by number of doses, having improved measles vaccine efficiency 10 to 20-fold by switching to MRC-5 cell culture instead of chicken eggs. In China, Sinopharm alone provides over 85 percent of the doses for 14 different vaccines. Preservatives matter because their absence can be deadly. In one 1928 incident, a diphtheria vaccine that lacked a preservative killed 12 of 21 children inoculated with it. A 10 to 11-year study of 657,461 children found that the MMR vaccine does not cause autism and actually reduced the risk by seven percent, yet the WHO still named vaccine hesitancy one of the top ten global health threats in 2019.