Booster vaccines for COVID-19 vaccine breakthrough cases?

We read with interest the Viewpoint by Philip Krause and colleagues.¹

Although considerations for boosting COVID-19 vaccine immune responses are surprisingly controversial, several existing non-COVID-19 vaccines have routine three-dose regimens to provide maximum efficacy. A recent study from Israel reinforces the value of a third vaccine dose in individuals aged 60 years or older² and the recent decision by the Food and Drug Administration to recommend an additional vaccination in those aged 65 years or older in the USA reflects the need to continue to protect the most vulnerable. Bar-On and colleagues show data supporting an additional dose,² but they do not cover efficacy of a third dose for someone who has had a breakthrough infection after full vaccination. These are individuals usually with no underlying known immunogenicity, who, nonetheless, for a variety of reasons (ie, higher exposure to viral inoculum, prolonged exposures to multiple infected people, or a previously undiagnosed mild immunodeficiency) become infected with SARS-CoV-2. Although there are many potential reasons for vaccine breakthroughs, including variants, it might be that a booster dose is most needed in those whose vaccine-induced immunity had already failed. Official data from Israel have shown that in those who receive a third dose, with or without breakthrough infection, there are potential side-effects, although similar to or better than after dose two of the primary series.³ Careful monitoring is needed for vaccine breakthrough cases since they might be the most susceptible to additional re-infections and might be most in need of another dose of vaccine.