H. responses were demonstrated in the DPX-RSV(A) 10-g and 25-g groups (geometric mean titer, approximately 10-fold and 100-fold greater than that of placebo at Zidebactam sodium salt days 56 and 236, respectively), and responses were sustained in the DPX-RSV(A) 25-g group at day 421. Responses to the RSV(A)-Alum vaccines were very low. Conclusions A novel antigen from the SH protein of RSV, formulated in a lipid and oilCbased vaccine platform, was highly immunogenic, with sustained antigen-specific antibody responses, and had an acceptable safety profile. tests and analysis of variance. Geometric mean antibody titers (GMTs) and their 95% CIs were calculated by group for each time point after vaccination. CIs for the difference of geometric means were calculated for the pair-wise comparison of groups. For each participant, the antibody titer was defined as the inverse of the highest dilution (starting at 1:100) of postvaccination serum above the cutoff, which was determined for each subject on the basis of the day 0 titer. Serum samples below the detection limit Rabbit Polyclonal to NRL were assumed to have an antibody titer of 50. These analyses were performed using statistical and summarization procedures in SAS, version 9.4 (Cary, NC). For the repeated measurement analysis, log-transformed ratios of GFP-positive cells to GFP-negative cells were analyzed as repeated measurements, using the residual maximum likelihood approach as implemented in Genstat, version 18 [12]. Briefly, a linear mixed model with treatment, time, and the treatment time interaction as fixed terms and subject time as a residual term was fitted to data. Times of measurement were set at unequal intervals, and the unstructured correlation structure was selected as the best model fit, based on the Akaike information coefficient. Significances of the fixed terms and significances of changes in differences between treatment effects over time were assessed by an F test. RESULTS Forty participants received the first dose of vaccine (Figure 1). The investigator withdrew 1 participant at the time of the second dose because of new-onset cutaneous herpes zoster. After data lock, this subject was noted to be in Zidebactam sodium salt the placebo group. On preordained review of immunogenicity results for participants in step 1 1 by the data safety monitoring committee, the second dose of vaccine at day 56 in the RSV(A)-Alum group was placebo, rather than RSV(A)-Alum. Characteristics of study participants are seen in Table 1. Table 1. Characteristics of Participants online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Supplementary FigureClick here for additional data file.(238K, ppt) Supplementary Figure LegendClick here for additional data file.(13K, docx) Supplementary TableClick here for additional data file.(16K, docx) Notes We thank the study participants for their contributions Zidebactam sodium salt to the study. This work was supported by the Canadian Institutes of Health Industry-Partnered Collaborative Research Operating Grant program and Immunovaccine. J. M. L., S. A. H., and S. A. M. have received research funding from GlaxoSmithKline, Immunovaccine, Sanofi Pasteur, Pfizer, Pan Provincial Vaccine Enterprise (Prevent), Novavax, the Public Health Agency of Canada, and the Canadian Institutes of Health Research. L. D. M., G. W., and M. S. are employees of Immunovaccine and own stock/share options or restricted shares of Immunovaccine. S. A. H. is a member of the Immunovaccine Advisory Board. VIB and UGent hold patent rights on SHe-based vaccines and treatment options Zidebactam sodium salt for RSV (patent application WO2012/065997 [24.05.2012]). B. S. and X. S. are named as inventors on this patent, which is licensed to Immunovaccine. Presented in part: IDWeek, New Orleans, Louisiana, 26C30 October 2016; 10th International RSV Symposium, Patagonia, Argentina, 28 SeptemberC1 October 2016; 17th World Vaccine Congress, Barcelona, Spain, 10C12 October 2016..