Dataset Information

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate.

ABSTRACT: The stability of live-attenuated viruses is very challenging due to thermal sensitivity; therefore, solid form is usually required (often freeze-dried products). Micropellet technology is a lyophilization technology that has the potential to provide greater flexibility in the presentation of a given vaccine particularly in multi-dose format or in combination of different vaccines. As a novel vaccine alternative process, this spray freeze-dried (SFD) micropellet technology was evaluated using as a model a yellow fever virus produced in Vero cells (vYF). Screening of excipients was performed in order to optimize physico-chemical properties of the micropellets. Sugar/polymer-based formulations induced high glass transition temperature (Tg), adequate breaking force and attrition resistance of the SFD micropellets. These mechanical parameters and their stability are of considerable importance for the storage, the transport but also the filling process of the SFD micropellets. By adding excipients required to best preserve virus infectivity, an optimal sugar/polymer-based formulation was selected to build micropellets containing vYF. Monodisperse and dried micropellets with a diameter of about 530 µm were obtained, exhibiting similar potency to conventional freeze-dried product in terms of vYF infectious titer when both solid forms were kept under refrigerated conditions (2-8 °C). Comparable kinetics of degradation were observed for vYF formulated in micropellets or as conventional freeze-dried product during an accelerated stability study using incubations at 25 °C and 37 °C over several weeks. The results from this investigation demonstrate the ability to formulate live-attenuated viruses in micropellets. Pharmaceutical applications of this novel vaccine solid form are discussed.

SUBMITTER: Clenet D

PROVIDER: S-EPMC6727866 | biostudies-other | 2019 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate.

Clénet Didier D Hourquet Véronique V Woinet Bertrand B Ponceblanc Hervé H Vangelisti Manuel M

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 20190712

The stability of live-attenuated viruses is very challenging due to thermal sensitivity; therefore, solid form is usually required (often freeze-dried products). Micropellet technology is a lyophilization technology that has the potential to provide greater flexibility in the presentation of a given vaccine particularly in multi-dose format or in combination of different vaccines. As a novel vaccine alternative process, this spray freeze-dried (SFD) micropellet technology was evaluated using as ...[more]

PMID: 31306751

Similar Datasets

Project description:The attenuated yellow fever (YF) vaccine is one of the most successful vaccines ever developed. After a single dose administration YF vaccine can induce balanced Th1/Th2 immune responses and long-lasting neutralizing antibodies. These attributes endorsed it as a model of how to properly stimulate the innate response to target protective immune responses. Despite their longstanding success, attenuated YF vaccines can cause rare fatal adverse events and are contraindicated for persons with immunosuppression, egg allergy and age < 6 months and >60 years. These drawbacks have encouraged the development of a non-live vaccine. The aim of the present study is to characterize and compare the immunological profile of two adjuvant formulations of an inactivated YF 17DD vaccine candidate. Inactivated YF vaccine formulations based on alum (Al(OH)3) or squalene (AddaVax®) were investigated by immunization of C57BL/6 mice in 3-dose or 2-dose schedules, respectively, and compared with a single dose of attenuated YF virus 17DD. Sera were analyzed by ELISA and Plaque Reduction Neutralization Test (PRNT) for detection of total IgG and neutralizing antibodies against YF virus. In addition, splenocytes were collected to evaluate cellular responses by ELISpot. Both inactivated formulations were able to induce high titers of IgG against YF, although neutralizing antibodies levels were borderline on pre-challenge samples. Analysis of IgG subtypes revealed a predominance of IgG2a associated with improved neutralizing capacity in animals immunized with the attenuated YF vaccine, and a predominance of IgG1 in groups immunized with experimental non-live formulations (alum and AddaVax®). After intracerebral (IC) challenge, attenuated and inactivated vaccine formulations showed an increase in neutralizing antibodies. The AddaVax®-based inactivated vaccine and the attenuated vaccine achieved 100% protection, and alum-based equivalent formulation achieved 70% protection.

Dataset Information

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate.

Publications

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets