Appropriate Sampling and Longer Follow-Up Are Required to Rigorously Evaluate Longevity of Humoral Memory After Vaccination.

One of the goals of vaccination is to induce long-lived immunity against the infection and/or disease. Many studies have followed the generation of humoral immunity to SARS-CoV-2 after vaccination; however, such studies typically varied by the duration of the follow-up and the number of time points at which immune response measurements were done. How these parameters (the number of time points and the overall duration of the follow-up) impact estimates of immunity longevity remain largely unknown. Several studies, including one by Arunachalam et al. (2023. J. Clin. Invest. 133: e167955), evaluated the humoral immune response in individuals receiving either a third or fourth dose of mRNA COVID-19 vaccine; by measuring Ab levels at three time points (prior to vaccination and at 1 and 6 mo), Arunachalam et al. found similar half-life times for serum Abs in the two groups and thus suggested that additional boosting is unnecessary to prolong immunity to SARS-CoV-2. I demonstrate that measuring Ab levels at these three time points and only for 6 mo does not allow one to accurately evaluate the long-term half-life of vaccine-induced Abs. By using the data from a cohort of blood donors followed for several years, I show that after revaccination with vaccinia virus, vaccinia virus-specific Abs decay biphasically, and even the late decay rate exceeds the true slow loss rate of humoral memory observed years prior to the boosting. Mathematical models of Ab response kinetics, parameterized using preliminary data, should be used for power analysis to determine the most appropriate timing and duration of sampling to rigorously determine the duration of humoral immunity after vaccination.