Vaccines are a cornerstone of public health, designed to protect individuals and communities from infectious diseases. When evaluating how well a vaccine works, researchers consider a spectrum of outcomes, from individual-level effects to broader population impacts. At the individual level, direct effects include reducing susceptibility to infection upon exposure to a pathogen. For diseases like rabies, the primary goal is to prevent infection entirely, as the disease is nearly always fatal once symptoms appear. For others, such as varicella (chickenpox), a key secondary benefit is reducing symptom severity in vaccinated individuals who still contract the infection.
For pathogens like influenza and COVID-19, the focus shifts to preventing severe outcomes, such as hospitalisation or death, which are critical public health priorities. Vaccines also mitigate disease progression, reducing the burden on healthcare systems. This direct protection is measured in terms of reduced incidence of infection, symptomatic disease, or severe morbidity and mortality among vaccinated individuals.
Beyond direct effects, vaccines offer indirect benefits by reducing the infectiousness of vaccinated individuals. If a vaccinated person becomes infected, the vaccine may lower the likelihood of transmitting the pathogen to others, protecting both vaccinated and unvaccinated contacts. This effect is particularly valuable in settings with close contact, such as households or healthcare facilities.
At the population level, herd immunity emerges as a critical outcome. When a significant proportion of a population is vaccinated, the reduced susceptibility of vaccinated individuals lowers the overall transmission rate. This protects unvaccinated people by decreasing their risk of exposure, as seen in the near-eradication of rubella and smallpox. Herd immunity amplifies the direct and indirect effects, potentially leading to disease elimination or eradication.
Vaccine efficacy is typically assessed in randomised controlled trials (RCTs), where participants are randomly assigned to vaccinated or unvaccinated groups. Randomisation ensures comparability, minimising confounding factors like age or health status. Common outcomes in RCTs include reduced infection acquisition, symptomatic illness, or severe disease. However, during public health emergencies, RCTs may be infeasible or unethical, as delaying vaccination could cost lives.
In 2022, the modified vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine was rapidly deployed in high-income countries to combat mpox, particularly among gay, bisexual, and other men who have sex with men, a group disproportionately affected during the outbreak. With limited prior evidence of efficacy against mpox, observational studies filled the gap. A study in Ontario, Canada, used clinical, laboratory, and administrative data to estimate a 58% effectiveness (95% CI 31% to 75%) against laboratory-confirmed mpox infection.
Observational studies face challenges, as outcomes often depend on testing access. The Ontario study focused on laboratory-confirmed cases, missing clinical diagnoses without testing—a common issue in resource-limited settings. It also couldn’t directly measure effectiveness against disease severity or indirect effects, though it suggested the vaccination programme contributed to slowing regional mpox transmission in 2022.
These findings highlight the complexity of vaccine evaluation. Direct effects like reduced susceptibility are foundational, but indirect effects and herd immunity amplify impact. Observational data, despite limitations, provide critical real-world evidence, guiding public health strategies during outbreaks and beyond.
