The World Health Organization Collaborating Center (WHO CC) for Vaccine Research, Evaluation and Training on Emerging Infectious Diseases in conjunction with the Paul-Ehrlich-Institut (P.E.I. - the German Federal Institute for Vaccines & Biologicals; equivalent to the Center for Biologics Evaluation and Research at the FDA), will sponsor an internship program during 2017. The internship program will support one (1) graduate/medical student, with the student spending three months at P.E.I. in Langen, Germany.
The successful applicant will be chosen by a combined WHO CC and P.E.I. selection committee. If selected, the intern will live in Langen and be paired with mentors at P.E.I. and the UTMB WHO CC. The work will be a defined project for a period of 3 months (to be scheduled during mid-July to late October 2017, exact dates to be determined). The intern will choose from one of two projects: 1) “Integrating NGS Analyses of Live-Attenuated Vaccines in the Regulatory Framework”, or 2) “Implementing 3R Approaches in Vaccine Batch Release Testing”. These projects will involve significant contribution to a team tasked with the evaluation of candidate and licensed vaccines and biomedicines for P.E.I. The SCVD will provide funds for expenses ($10,000 for three months, plus cost of flights) plus stipend while the student is in Germany. For academic purposes, the internship will be treated as a graded graduate course elective with credit.
We believe this program represents an outstanding career development opportunity for UTMB’s students/trainees and will provide the successful intern with first-hand experience of research and regulatory considerations for development of vaccines and other biological products. The WHO CC will facilitate the application process and work with P.E.I. on the project design and implementation.
For more information, please contact Drs. David Beasley (email@example.com), Gregg Milligan (firstname.lastname@example.org), Lisa Reece (email@example.com), or Alan Barrett (firstname.lastname@example.org). Please email Dr. Reece for application forms.
The deadline for applications is close-of-business Thursday, March 23, 2017. All successful applicants must have written support from their mentor and/or program director for their participation in the internship program.
Project areas are described below. Minor adjustments to the projects may be made to accommodate new developments in the field.
1. Integrating NGS analyses of live-attenuated vaccines in the regulatory framework
The advances in next generation sequencing (NGS) allow an investigation of the genetic diversity at hitherto unknown depth. In the context of vaccine production, this technology has the potential to provide insights in the purity and genetic stability of attenuated vaccine strains throughout the production process. This requires a definition of interpretation criteria based on comparative data sets for different product groups and the subsequent integration in the regulatory framework.
In this project, the student will generate a comprehensive overview of the current state of knowledge, taking into account the available WHO (World Health Organization), EMA (European Medicines Agency), FDA (US Food and Drug Administration, and ICH (International Conference on Harmonization) guidelines and general literature regarding NGS applications in vaccine batch release and extraneous agents testing.
In parallel, the student will participate in the ongoing assessment of the genetic diversity found in different batches of live-attenuated vaccines from different producers against the same pathogens. This practical aspect of the project includes the preparation of the sample for NGS analysis as well as the subsequent bioinformatics analysis of the data. The results obtained will contribute to the database used to advance the relevant guidelines.
Hoper D, Freuling CM, Muller T, Hanke D, von Messling V, Duchow K, Beer M, Mettenleiter TC. High definition viral vaccine strain identity and stability testing using full-genome population data - The next generation of vaccine quality control. Vaccine. 2015;33:5829-37.
2. Implementing 3R approaches in vaccine batch release testing
Many of the assays required for the batch release of vaccines still involve animal experiments. There is thus an ongoing effort to refine the experiments to lessen suffering, to reduce the overall number of animals needed to obtain the result, and to replace animal experiments with in vitro methods (3R). Once such method has been developed. It has to be added to the pharmacopoeia monograph of the respective product which involves extensive validation and collaborative studies with several accredited laboratories.
In this project, the student will review vaccine monographs in the European and American Pharmacopoeias and the regulatory literature, to generate an overview of animal tests that are still required. The tests will then be further evaluated regarding their potential for the development of an in vitro replacement method.
In parallel, the student will assist in the initiation and realization of a collaborative study for the validation of an in vitro assay to quantify the activity of botulinum neutrotoxins (BoNT). This involves the quality control of the reagents prior to shipment to the participating laboratories, communication and troubleshooting with the participating laboratories during the experimental phase, and analysis and interpretation of the data obtained. The results of the collaborative study will constitute the rationale for including this alternative method in the BoNT monograph.
Wild E, Bonifas U, Klimek J, Trosemeier JH, Kramer B, Kegel B, Behrensdorf-Nicol HA. In vitro potency determination of botulinum neurotoxin B based on its receptor-binding and proteolytic characteristics. Toxicol In Vitro. 2016; 34:97-