Alternative administration routes and delivery technologies for polio vaccines.

Global polio eradication is closer than ever. Replacement of the live attenuated oral poliovirus vaccine (OPV) by inactivated poliovirus vaccine (IPV) is recommended to achieve complete eradication. Limited global production capacity and relatively high IPV costs compared to OPV spur the need for improved polio vaccines. The target product profile of these vaccines includes not only dose sparing but also high stability, which is important for stockpiling, and easy application important for (emergency) vaccination campaigns. In this review, the current status of alternative polio vaccine delivery strategies is given. Furthermore, we discuss the feasibility of these strategies by highlighting challenges, hurdles to overcome, and formulation issues relevant for optimal vaccine delivery

A New Strategy to Stabilize Oxytocin in Aqueous Solutions: I. The Effects of Divalent Metal Ions and Citrate Buffer

In the current study, the effect of metal ions in combination with buffers (citrate, acetate, pH 4.5) on the stability of aqueous solutions of oxytocin was investigated. and divalent metal ions (Ca2+, Mg2+, and Zn2+) were tested all as chloride salts. The effect of combinations of buffers and metal ions on the stability of aqueous oxytocin solutions was determined by RP-HPLC and HP-SEC after 4 weeks of storage at either 4°C or 55°C. Addition of sodium or potassium ions to acetate- or citrate-buffered solutions did not increase stability, nor did the addition of divalent metal ions to acetate buffer. However, the stability of aqueous oxytocin in aqueous formulations was improved in the presence of 5 and 10 mM citrate buffer in combination with at least 2 mM CaCl2, MgCl2, or ZnCl2 and depended on the divalent metal ion concentration. Isothermal titration calorimetric measurements were predictive for the stabilization effects observed during the stability study. Formulations in citrate buffer that had an improved stability displayed a strong interaction between oxytocin and Ca2+, Mg2+, or Zn2+, while formulations in acetate buffer did not. In conclusion, our study shows that divalent metal ions in combination with citrate buffer strongly improved the stability of oxytocin in aqueous solutions

Oxytocin formulations and uses thereof

The present invention relates to the field of preventive and therapeutic medicine, in particular to peptide formulations. Provided is a p H-buffered aqueous formulation comprising oxytocin, vasopressin or an analogue thereof and at least one non-toxic source of divalent metal ions in a concentration of at least 2 m M, and the use of the formulation for the manufacture of a medicament for therapeutic and/or prophylactic treatments. Also provided is a method for treating or preventing haemorrhage in a subject in need thereof, comprising administering to said subject an effective dosage amount of an oxytocin formulation according to the invention. Further provided is a method for treating or preventing diabetes insipidus or vasodilatory shock in a subject in need thereof, comprising administering to said subject an effective dosage amount of a vasopressin formulation according to the invention

Peptide formulations and uses thereof

The present invention relates to the field of preventive and therapeutic medicine, in particular to peptide formulations. Provided is a p H-buffered aqueous formulation comprising oxytocin, vasopressin or an analogue thereof and at least one non-toxic source of divalent metal ions in a concentration of at least 2 m M, and the use of the formulation for the manufacture of a medicament for therapeutic and/or prophylactic treatments. Also provided is a method for treating or preventing haemorrhage in a subject in need thereof, comprising administering to said subject an effective dosage amount of an oxytocin formulation according to the invention. Further provided is a method for treating or preventing diabetes insipidus or vasodilatory shock in a subject in need thereof, comprising administering to said subject an effective dosage amount of a vasopressin formulation according to the invention

A Design of Experiment approach to predict product and process parameters for a spray dried influenza vaccine

AbstractSpray dried vaccine formulations might be an alternative to traditional lyophilized vaccines. Compared to lyophilization, spray drying is a fast and cheap process extensively used for drying biologicals. The current study provides an approach that utilizes Design of Experiments for spray drying process to stabilize whole inactivated influenza virus (WIV) vaccine. The approach included systematically screening and optimizing the spray drying process variables, determining the desired process parameters and predicting product quality parameters. The process parameters inlet air temperature, nozzle gas flow rate and feed flow rate and their effect on WIV vaccine powder characteristics such as particle size, residual moisture content (RMC) and powder yield were investigated. Vaccine powders with a broad range of physical characteristics (RMC 1.2–4.9%, particle size 2.4–8.5μm and powder yield 42–82%) were obtained. WIV showed no significant loss in antigenicity as revealed by hemagglutination test. Furthermore, descriptive models generated by DoE software could be used to determine and select (set) spray drying process parameter. This was used to generate a dried WIV powder with predefined (predicted) characteristics. Moreover, the spray dried vaccine powders retained their antigenic stability even after storage for 3 months at 60°C. The approach used here enabled the generation of a thermostable, antigenic WIV vaccine powder with desired physical characteristics that could be potentially used for pulmonary administration

The effect of formulation on spray dried Sabin inactivated polio vaccine

The objective of this study was to develop a stable spray dried formulation, containing the three serotypes of Sabin inactivated polio vaccine (sIPV), aiming for minimal loss of native conformation (D-antigen) during drying and subsequent storage. The influence of atomization and drying stress during spray drying on trivalent sIPV was investigated. This was followed by excipient screening, in which monovalent sIPV was formulated and spray dried. Excipient combinations and concentrations were tailored to maximize both the antigen recovery of respective sIPV serotypes after spray drying and storage (T = 40 °C and t = 7 days). Furthermore, a fractional factorial design was developed around the most promising formulations to elucidate the contribution of each excipient in stabilizing D-antigen during drying. Serotype 1 and 2 could be dried with 98% and 97% recovery, respectively. When subsequently stored at 40 °C for 7 days, the D-antigenicity of serotype 1 was fully retained. For serotype 2 the D-antigenicity dropped to 71%. Serotype 3 was more challenging to stabilize and a recovery of 56% was attained after drying, followed by a further loss of 37% after storage at 40 °C for 7 days. Further studies using a design of experiments approach demonstrated that trehalose/monosodium glutamate and maltodextrin/arginine combinations were crucial for stabilizing serotype 1 and 2, respectively. For sIPV serotype 3, the best formulation contained Medium199, glutathione and maltodextrin. For the trivalent vaccine it is therefore probably necessary to spray dry the different serotypes separately and mix the dry powders afterwards to obtain the trivalent vaccine.</p

Development of cross-protective influenza a vaccines based on cellular responses

Seasonal influenza vaccines provide protection against matching influenza A virus (IAV) strains mainly through the induction of neutralizing serum IgG antibodies. However, these antibodies fail to confer a protective effect against mismatched IAV. This lack of efficacy against heterologous influenza strains has spurred the vaccine development community to look for other influenza vaccine concepts, which have the ability to elicit cross-protective immune responses. One of the concepts that is currently been worked on is that of influenza vaccines inducing influenza-specific T cell responses. T cells are able to lyse infected host cells, thereby clearing the virus. More interestingly, these T cells can recognize highly conserved epitopes of internal influenza proteins, making cellular responses less vulnerable to antigenic variability. T cells are therefore cross-reactive against many influenza strains, and thus are a promising concept for future influenza vaccines. Despite their potential, there are currently no T cell-based IAV vaccines on the market. Selection of the proper antigen, appropriate vaccine formulation and evaluation of the efficacy of T cell vaccines remains challenging, both in preclinical and clinical settings. In this review, we will discuss the current developments in influenza T cell vaccines, focusing on existing protein-based and novel peptide-based vaccine formulations. Furthermore, we will discuss the feasibility of influenza T cell vaccines and their possible use in the future.Drug Delivery Technolog