2 Specificity and sensitivity of a risk factor-based score for HBV vaccine responder status. at main vaccination (24.0 (R) vs. 30.5 (NR) vs. 31 (LR) years, em p /em ?=?0.001), higher median BMI (23.2?kg/m2 (R) vs. 23.4?kg/m2 (NR) vs. 25.1?kg/m2 (LR), p?=?0.001) and being a smoker (% smokers: 30.8% (R) vs. 57.1% (NR) vs. 52.5% (LR), em p /em ?=?0.01) as factors negatively associated with anti-HBs-IgG levels. In a ROC analysis including these factors in a 6-point score, a high score predicted non-response with a specificity of 85% but at low sensitivity (47%). Conclusion A simple clinical risk score based on age, obesity, and smoking identifies individuals with a high likelihood of vaccine failure. nonresponders with a low score are candidates for in-depth analyses to better understand the immunological causes of HBV vaccine non-response. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-020-05634-y. strong class=”kwd-title” Keywords: Hepatitis B, Vaccine, Non-response, HBs, Antibodies, Smoking, Age, BMI, Risk score PR-171 (Carfilzomib) Background Chronic Hepatitis B computer virus (HBV) infection affects about 400 million individuals worldwide, and cumulatively accounts for about 1 million deaths annually . Vaccination against HBV is usually safe and very effective in preventing HBV infection and its complications . Since the early 1990s, high-risk populations -especially health care workers- have been systematically vaccinated. More recently, vaccination efforts have been extended and many national vaccination programs now recommend HBV vaccination for the general populace. The currently available HBV vaccine preparations use recombinant hepatitis B surface antigen (HBsAg) as the antigen. Vaccination induces an antibody-based protective immunity targeting the HBsAg [3, PR-171 (Carfilzomib) 4]. Main immunization protects at least two decades in the vast majority of immunocompetent individuals . An anti-HBs antibody titer above 100?IU/L is considered protective, whereas titers below 10?IU/L confer no reliable protection from infection. Accordingly, vaccine recipients are graded into non-responders ( ?10?IU/L), low-responders (10C100?IU/L), and responders ( ?100?IU/L), respectively . Large vaccination studies suggested nonresponder rates in the range of 5 to 10% of all HBV vaccinated healthy individuals vaccinated using the standard vaccination regimen . Several epidemiological studies have established that age at immunization, overweight, gender, smoking status, co-morbidities and immunosuppression impact the vaccine response [6C15]. In many of the subjects with these risk factors, protective immunity can be achieved by repeated additional doses (booster) . The reason for the failure to adequately respond to HBV vaccination in subjects without classical risk factors has been attributed to genetic factors (MHC), reduced T cell activation or failure of the T cells to recognize the HBs Ag (hole in the repertoire) . Here, we analyzed a group of hepatitis B vaccine non-responders and tested, if a simple score based on age, and -the potentially modifiable life-style factors- BMI and smoking status may allow selecting subjects with a high likelihood for vaccine failure. PR-171 (Carfilzomib) Methods Vaccine recipient cohorts and screening strategy The local Ethical committee (EKNZ-265/12) approved the study. We performed a retrospective database screening of HBs-IgG test results collected between 1995 and 2012. We limited our analysis on potential non-responders from your medical outpatient medical center, the vaccination medical center and occupational health service (OHS), in order to exclude subjects with relevant comorbidities. We excluded subjects with only a single anti-HBs-IgG measurement, and we divided the remaining into potential non-responders (all measurements ?100?IU/L) vs. responders (at least one measurement ?100?IU/L). For the patients chart review of all potential non-responders we excluded subjects with (i) no chart available; (ii) incomplete main vaccination schedules; (iii) obvious immunosuppression (i.e. chemotherapy, HIV, active cancer, immunosuppressive drugs); (iv) documented titers ?100?IU/L in RGS10 the chart, (v) age? ?60 at main immunization, or (v) natural HBV infection. As a control group, 134 subjects with well-documented vaccination schedules and demographic factors were selected from your responder pool. The screening and subject selection process is usually summarized in Physique S1. Data collection for all those studied subjects included: anti-HBs-IgG levels, vaccine preparation/brand, vaccination routine, demographic and way of life factors (age, gender, BMI, smoking habits). Besides, total white blood cell count (WBC), neutrophil count, and lymphocyte PR-171 (Carfilzomib) count were also extracted from your charts, if these.