Center for Biologics Evaluation and Research

About: Center for Biologics Evaluation and Research is a facility organization based out in Silver Spring, Maryland, United States. It is known for research contribution in the topics: Virus & Vaccination. The organization has 3024 authors who have published 4648 publications receiving 228078 citations. The organization is also known as: CBER.

The Food and Drug Administration's Post‐Licensure Rapid Immunization Safety Monitoring program: strengthening the federal vaccine safety enterprise

Abstract: In 2009, the Department of Health and Human Services created the new Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program, which used data from national health insurance plans and immunization registries to monitor the safety of the H1N1 influenza vaccine. PRISM has now been integrated into the FDA's Mini-Sentinel pilot program. It strengthens the federal vaccine safety enterprise in two important ways. First, PRISM monitors the largest US general population cohort designated for active surveillance of vaccine safety. Second, PRISM links data from health plans with data from state and city immunization registries, which were a crucial source of exposure data in the H1N1 vaccine evaluation. The Mini-Sentinel data that support PRISM are updated quarterly, and PRISM can conduct medical record review for validation of computerized data. The FDA has structured PRISM as a program that includes specific vaccine evaluations, development of an operational framework to guide the design of vaccine safety evaluations, and development of new statistical methods. A human papillomavirus vaccine, Gardasil, and two rotavirus vaccines, RotaTeq and Rotarix, have been chosen for surveillance in the current cycle because their evaluations would benefit most from PRISM's large cohort size. The PRISM program creates important opportunities by offering a robust, responsive new surveillance program with features complementary to existing systems. Methodological and logistical lessons can be shared among PRISM and other surveillance systems, offering potential synergies. FDA and PRISM will work to maximize the program's unique strengths and contributions to a unified federal vaccine safety enterprise.

Syncope after immunization.

Abstract: Objective: To describe the individual characteristics, clinical features, and morbidity associated with syncope following immunization. Design: Large case series. Setting: United States, 1990 through 1995. Subjects: Reports to the national Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system. An additional 3 reports of head injury (documented by medical records) were obtained through the National Vaccine Injury Compensation Program. Main Outcome Measures: Syncope, syncope and hospitalization, or syncope and head injury within 12 hours of vaccination. Results: A total of 697 cases of syncope after vaccination was reported. Age younger than 20 years was reported for 77.4%; 57.5% were female. Hospitalization was reported in 9.6%. Of the 571 syncope events with known time, 511 occurred 1 hour or less after vaccination. Of these, 323 (63.2%) occurred 5 minutes or less, 454 (88.8%) occurred 15 minutes or less, and 500 (97.8%) occurred 30 minutes or less after vaccination. Tonic or clonic movements, which have been associated with the anoxia of vasovagal syncope, were reported in 30.4% of syncopal episodes occurring 15 minutes or less after and in 12.8% of those occurring 15 minutes or longer after vaccination ( P Conclusions: Prevention of injury from syncope after vaccination and of syncope itself may be possible in many cases. Vaccinators should be aware that patients exhibiting presyncopal signs and symptoms around the time of immunization need to be evaluated carefully and may need to be assisted to sit or lie down after immunization until free of symptoms. Arch Pediatr Adolesc Med. 1997;151:255-259

Differential utilization of Janus kinase-signal transducer activator of transcription signaling pathways in the stimulation of human natural killer cells by IL-2, IL-12, and IFN-alpha.

Abstract: IL-2-, IL-12-, and IFN-alpha-mediated signaling pathways were analyzed in primary NK cells and in the NK3.3 cell line. Gel mobility shift and immunoprecipitation analyses revealed that in addition to activating STAT3 (signal transducer and activator of transcription-3) and STAT5, IL-2 induced tyrosine and serine phosphorylation of STAT1 alpha, which formed IFN-gamma-activated sequence-binding complexes by itself and with STAT3. Although IL-2 and IFN-alpha activated STAT1 alpha and STAT5, IL-2 predominantly activated STAT5, while IFN-alpha predominantly activated STAT1 alpha. IL-2 induced less STAT1 alpha activation and IFN-alpha induced greater STAT5 activation in NK3.3 cells compared with preactivated primary NK cells. In NK3.3 cells, IL-2 induced comparable formation of c-fos promoter sis-inducible element IFN-gamma-activated sequence-binding complexes containing STAT3 alone with complexes containing STAT3 and STAT1 alpha, while in preactivated primary NK cells, it preferentially induced complexes containing STAT3 and STAT1 alpha. Thus, signaling in NK3.3 cells is not always identical with that in primary NK cells. In contrast to IL-2 and IFN-alpha, IL-12 induced strong tyrosine phosphorylation of STAT4 and variable weak phosphorylation of STAT3. However, supershift analyses using the c-fos promoter sis-inducible element probe showed that IL-12 activated STAT4, STAT1 alpha, and STAT3, and induced complexes containing STAT4 only, STAT4 with STAT1 alpha, STAT3 with STAT1 alpha, or STAT1 alpha only in preactivated primary NK cells. STAT1 alpha activation by IL-12 correlated with increased phosphorylation of serine, but not tyrosine. Finally, IL-2 induced tyrosine phosphorylation of JAK1 and JAK3, while IL-12 induced phosphorylation of JAK2 and TYK2 in both preactivated primary NK and NK3.3 cells. Differential phosphorylation and consequent differential activation of both separate and overlapping STAT proteins by IL-2, IL-12, and IFN-alpha may provide a molecular basis for the similarities and differences in the actions of these cytokines on NK cells.

Expression of Neisseria meningitidis iron-regulated outer membrane proteins, including a 70-kilodalton transferrin receptor, and their potential for use as vaccines.

Abstract: The iron-regulated proteins (IRPs) of five group B meningococcal strains expressing class 2 outer membrane proteins were compared with those of five strains expressing class 3 proteins. Three to four high-molecular-weight IRPs were expressed by each strain, but their molecular sizes varied between strains and were not related to class 2 or 3 protein expression. Transferrin and hemoglobin could be used as a sole iron source. By using anti-human transferrin antibodies, it was shown that meningococcal cells and purified outer membranes bound transferrin. Growth under conditions of iron limitation caused a several-fold increase in the amount of transferrin bound to the cell surface. The transferrin-binding protein was detergent solubilized from outer membranes and partially purified. The isolated protein bound human transferrin and had an apparent molecular mass of 70 kilodaltons. To evaluate the potential of vaccines containing IRPs, we prepared outer membrane vaccines from strains M986-NCV-1 (M986) (--:2a: P1.2) and 44/76-M25 (44/76) (--:15:P1.15) grown to fully express their IRPs. Both vaccines induced significant anti-IRP antibodies as measured by enzyme immunoassay and by Western immunoblot with both M986 and 44/76 outer membranes. By Western blot analysis, the M986 vaccine induced antibodies to two different IRPs, one of which was shared with 44/76. Since the IRPs are major in vivo-expressed outer membrane proteins and are required for survival in vivo, these proteins should be evaluated for their usefulness in a group B meningococcal vaccine. Images