A fundamental difference between the immune responses generated by vaccines and natural infection is their specificity. In a natural infection, whole SARS-CoV-2 viruses infect cells in the respiratory tract. Responding immune cells can target any number of facets of those whole viruses. This creates a relatively large diversity of antibodies that bind to different bits of SARS-CoV-2. The vaccines, meanwhile, only serve up to the immune system key snippets of SARS-CoV-2—namely the virus’ spike protein. This is the protein that SARS-CoV-2 uses to enter human cells, and it’s a key target of neutralizing antibodies. All antibodies in vaccinees will target the spike protein. Though vaccinees have less antibody diversity than previously infected people, they have high levels of highly targeted antibodies. Think of it as the difference between hunting a tiny virus with a shotgun and a sniper rifle.

With variable immune responses after infection comes variable real-world data on how well past infection protects against reinfection, which has led to the different public policy approaches. In a study conducted at Cleveland clinic and posted online in June, researchers found that among 52,238 employees, there were no differences in COVID-19 case rates between employees who were unvaccinated but previously infected, vaccinated and previously infected, and vaccinated people with no previous infection. “Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination,” the authors concluded.

Yet, in another study published in August by the Centers for Disease Control and Prevention, researchers looked at the vaccination status of more than 200 Kentucky residents who had tested positive for SARS-CoV-2 in 2020 and then tested positive again during May and June 2021. The CDC researchers found that people previously infected but unvaccinated were 2.34 times more likely to get reinfected than people who were previously infected and fully vaccinated.