Dr. Scott Halperin, a pediatric infectious disease specialist and director of the Canadian Center for Vaccinology, frames it this way: “Vaccines try to simulate what a natural infection would do, without the risk of the disease. Sometimes we use a weakened version of the virus, such as for measles. Other times we use just the problem piece, the toxin or a surface protein, and train the immune system to recognize that.” The measles vaccine uses a live-attenuated virus that can trigger mild, self-limited symptoms in a small fraction of recipients; the immune system learns enough to prevent disease when the wild virus appears. Tetanus vaccines, by contrast, contain a modified, detoxified version of the toxin. “You’re not immunized with the bacterium,” Dr. Halperin says. “You’re immunized against the poison it makes.” For Dr. Sadarangani, the path to vaccine research began with curiosity about the constant struggle between humans and microbes. “These pathogens evolve much faster than we do,” he says. “Some bacteria can double every 20 minutes. They’re always changing.” That dynamic drew him toward infectious diseases, but prevention was what truly captured his imagination. “I’ve always been more of a prevention person than a treatment person,” he explains. “Getting ahead of disease has a far bigger impact than treating it after the fact.” For him, vaccines are the purest form of that idea: using science to give the immune system an advantage in an endless biological contest. A Brief History: From Cowpox to Code The intellectual roots of vaccination reach back to the late 18th century. “It goes back to Edward Jenner and smallpox,” Dr. Tunis says. “And taking a less pathogenic version of a virus and exposing the immune system so it’s ready for the real thing.” Early technologies often used whole organisms that were either killed or weakened. The portfolio of vaccines expanded in the early- and mid-20th century with vaccines against diphtheria, tetanus and pertussis, followed by polio and the measles–mumps– rubella (MMR) combination in the 1960s and 70s. “We went from a handful to a dozen vaccines,” Dr. Halperin says. “Since then, growth has followed an exponential path. The decades near the end of the 20th century brought powerful conjugate vaccines against Haemophilus influenzae type b and Streptococcus pneumoniae; newer formulations steadily widened the serotype coverage and reduced disease. Eradication of smallpox became a public health milestone. Polio has been eliminated from most of the world, with endemic transmission remaining in only two countries, Pakistan and Afghanistan.” Technology has become increasingly precise. Rather than relying primarily on live-attenuated or whole-cell approaches, many modern vaccines deploy purified protein subunits, polysaccharides (often conjugated to proteins to improve immune response), virus-like particles, or most recently nucleic-acid platforms that instruct our own cells to make the relevant viral protein. “As you get more focused on specific components, sometimes you need adjuvants to boost the signal,” Dr. Tunis says. The goal is to present the immune system with the right target, at the right dose, with the right stimulation, which maximizes protection and minimizes risk. The speed and scalability of mRNA platforms during the COVID-19 pandemic were a watershed. Expectations set before those trials, which were 50–70% efficacy, were eclipsed by initial results showing around 95% efficacy against symptomatic disease for the original strains. As we age, immune responses can wane, a phenomenon called immune senescence, so vaccine formulations for older adults may include higher antigen doses or adjuvants. The durability of that immune memory varies. With measles, immunity is “very long lived and robust,” Dr. Tunis says, especially after a two-dose series. But other pathogen–host combinations are less stable. As we age, immune responses can wane, a phenomenon called immune senescence, so vaccine formulations for older adults may include higher antigen doses or adjuvants; ingredients that enhance immune activation. Pathogens can also change. Influenza reshuffles its genetic deck each year; SARS-CoV-2 has evolved rapidly since 2020. Some bacteria exist in multiple serotypes that rise and fall in the population, prompting periodic updates to vaccine composition. But falling antibody levels in an individual do not always mean a loss of protection. “The immune system has to maintain homeostasis,” Dr. Tunis says. “Antibodies naturally decline after a peak, but memory B and T cells remain. On re-exposure, by booster or by the environment, the system quickly snaps back to high output.” Dr. Manish Sadarangani, a pediatric infectious diseases physician and director of the Vaccine Evaluation Center at BC Children’s Hospital, underscores that vaccines are ultimately about prevention, aligning with dentistry’s overarching ethos. “Great vaccines are only great once you can get them into people,” he says. The science prepares the immune system; the vaccination program delivers the protection. 21 Issue 2 | 2026 | Issues and People
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