The primary series can be thought of as the high school for lymphocytes, where naïve cells receive basic instructions to learn about the pathogen. Boosters are like a college where lymphocytes are further educated to become more skilled and mature, to fight off future infections. Periodically, these college graduates need refreshers by more booster doses given later in life. This is the case for all vaccines. Booster doses provide the immune system the education it needs to prevent severe diseases from infections.

COVID-19 vaccines also need booster doses for the same reasons. We need to educate, maintain, and improve T and B cell responses to prevent severe disease. Boosters provide significant benefits to people who received the primary series in preventing hospitalization and death. In the U.S. in April 2022, people older than 50 years of age who received no vaccine, primary series only (no booster dose), or one booster dose had 38 x, 6 x, or a 4 x higher risk, respectively, of dying from COVID-19 compared to those with two or more booster doses. During the Omicron-predominant period, the booster dose provided protection from hospitalization even in previously infected people, whether older (>65 years of age) or younger (<65 years of age). Among children and adolescents, a primary series (two doses) of vaccination was less effective in preventing COVID-19-associated emergency department and urgent care encounters during the Omicron wave compared to the Delta period. Immunity also decreases with time since primary vaccination. No significant protection was detected more than five months after a 2nd vaccine dose among adolescents aged 16–17 years. However, a third booster dose restored vaccine effectiveness to 81% in this age group. There is thus a clear benefit of a booster dose across a broad range of age groups studied to date.