Response to BNT162b2 mRNA COVID-19 vaccine among healthcare workers in Italy: a 3-month follow-up-Reply.

Dear Editor,

We read with interest the letter by Serraino and colleagues [1] as they report on our recent study about antibody response to BNT162b2 mRNA COVID-19 vaccine [2].

As a result of the swift development of vaccines for COVID-19 and immunization efforts worldwide, real-world data (RWD) have been collected among several populations and settings confirming vaccination safety, immunogenicity, and efficacy. In so doing, these studies have brought to attention important aspects toward understanding tailored intervention approaches to maximize vaccination campaigns worldwide.

Serraino and colleagues [1] report a greater boosting of antibody concentrations when vaccines were administered 2 months or more after SARS-CoV-2 diagnosis, confirming the observations about the role of prior SARS-CoV-2 infection in immune priming [2, 3].

It is also in agreement with a recent study of cellular and humoral responses to the first BNT162b2 vaccine dose in previously infected individuals who developed a stronger booster response when the interval between infection and vaccination was extended [4].

Possible explanations for these results have been speculated including a role for memory B cells, whose clonal turnover may modulate the antibody sequence evolution after the first BNT162b2 dose in previously infected subjects [5]. Further research is needed on the functional response of the cellular immune system following SARS-CoV-2 infections and COVID-19 vaccination over different time periods.

Presently, there are insufficient data to draw firm conclusions about the optimal timing of a single vaccination dose following infection and a number of factors that limit the comparability of vaccine data across studies, including differences in study design, population and setting. Nonetheless, the practice evidence presented by Serraino and colleagues provides a useful metric to implement the most appropriate vaccination prioritization strategies, particularly in the context of continuous monitoring of vaccine immunogenicity and effectiveness, as well as safety surveillance.

Collectively, the work by Serraino and colleagues, together with our findings [2, 3], suggest how important it is to use data derived from analysis of real-world evidence to understand how COVID-19 vaccines are helping control the pandemic and to tailor the most appropriate population-level interventions to protect against COVID-19.