No specific end points have been described for rabies immunogenicity after booster immunization. or not the individual has received a preventive immunization schedule, so called pre-exposure prophylaxis (PrEP) [1, 2]. In any case, post-exposure prophylaxis (PEP) consists of prompt wound care and the administration of anti-rabies vaccinations. In the case of a UTP14C nonimmunized or immunocompromised individual, this is an elaborate vaccination schedule of 4C5 vaccinations supplemented with the administration of rabies immunoglobulins (RIG) [1, 2]. Unfortunately, access to RIG is often limited or nonexistent in low- and middle-income countries where rabies is endemic [2]. The rationale for the administration of RIG is passive immunization to cover the period between administration of the vaccine and the mounting of an active immune response [3]. If an immune-competent individual has ever received PrEP, there is no need for RIG after exposure because of the presumed existence of rabies memory B cells formed after initial immunization. These memory cells allow an accelerated anamnestic neutralizing antibody response upon booster vaccination, the so-called boostability [1C5]. International guidelines suggest lifelong boostability by PEP if preceded by a complete course of PrEP [2]. In a recent systematic review and meta-analysis by Langedijk et al, only 2 studies were available that described booster responses more than 10 years after administration of PrEP or PEP with currently licensed immunizations [6]. The first study reported on 9 exposed individuals who had received PEP 32 years before their booster immunization [7]. Adequate booster responses were measured 30 days after immunization; this was considerably late as current guidelines suggest that the anamnestic rabies antibody response should be measured no later than 1 week after booster immunization [2, 3, 5C7]. The second study described adequate booster responses measured within 7 days after immunization of 53 subjects, who had received either PEP (38 subjects) or only PrEP (15 subjects), 10C21 years before booster immunization [8]. The current World Health Organization (WHO) recommendations state that both PrEP and PEP schedules induce lifelong boostable memory, which is mainly supported by data on booster vaccination within 10 years of primary immunization. Beyond 10 years, however, PrEP boostability with still licensed vaccines are only based Busulfan (Myleran, Busulfex) on an observation of 15 individuals who had received a 3-dose PrEP schedule. With our study, we aimed to add more evidence to the assumption that PrEP conveys long-term boostable immunologic memory [9, 10]. WHO considers a titer above 0.5 IU/mL as adequate [2]. No specific end points have been described for rabies immunogenicity after booster immunization. In general, a 4-fold increase in antibody titers is considered an adequate booster response, for example in meningococcal polysaccharide vaccines [11]. We tested the hypothesis that all participants who had received PrEP longer than 10 years ago would develop an adequate rabies titer Busulfan (Myleran, Busulfex) of??0.5 IU/mL within 1 week after boosting. METHODS Study Design and Procedure This multicenter, prospective, observational study comprised subjects who had undergone different rabies PrEP immunization schedules at least 10 years prior. When the study started in 2016, the officially approved WHO rabies PrEP Busulfan (Myleran, Busulfex) schedule consisted of a 3-dose immunization sequence, administered on days 0, 7, and 21C28. As of April 2018, the WHO endorsed a 2-dose PrEP schedule for immune-competent individuals. We intended to include 30 participants in total. Blood samples were taken prior to administration of a single intramuscular (IM) booster immunization, as well as on days 3, 7, and 14 after immunization. Study End Points The primary.