Meta-Analysis of Pulmonary Transcriptomes from Differently Primed Mice Identifies Molecular Signatures to Differentiate Immune Responses following Challenge.

Respiratory infection with leads to severe effects in the lungs. The resulting immunity and also immunization with pertussis vaccines protect against disease, but the induced type of immunity and longevity of the response are distinct. In this study the effects of priming, by either vaccination or infection, on a subsequent pathogen encounter were studied.

Bordetella pertussis outer membrane vesicle vaccine confers equal efficacy in mice with milder inflammatory responses compared to a whole-cell vaccine.

The demand for improved pertussis vaccines is urgent due to the resurgence of whooping cough. A deeper understanding of the mode of action of pertussis vaccines is required to achieve this improvement. The vaccine-induced effects of a candidate outer membrane vesicle vaccine (omvPV) and a classical protective but reactogenic whole cell vaccine (wPV) were comprehensively compared in mice.

Immunological Signatures after Bordetella pertussis Infection Demonstrate Importance of Pulmonary Innate Immune Cells.

Effective immunity against Bordetella pertussis is currently under discussion following the stacking evidence of pertussis resurgence in the vaccinated population. Natural immunity is more effective than vaccine-induced immunity indicating that knowledge on infection-induced responses may contribute to improve vaccination strategies. We applied a systems biology approach comprising microarray, flow cytometry and multiplex immunoassays to unravel the molecular and cellular signatures in unprotected mice and protected mice with infection-induced immunity, around a B.

The Production of a Stable Infliximab Powder: The Evaluation of Spray and Freeze-Drying for Production.

In prospect of developing an oral dosage form of Infliximab, for treatment of Crohn's disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) and spray-drying were investigated as production method for stable powders. Dextran and inulin were used in combination with sucrose as stabilizing excipients. The drying processes did not affect Infliximab in these formulations, i.

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

Spray 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.

Influenza Vaccine Manufacturing: Effect of Inactivation, Splitting and Site of Manufacturing. Comparison of Influenza Vaccine Production Processes.

The aim of this study was to evaluate the impact of different inactivation and splitting procedures on influenza vaccine product composition, stability and recovery to support transfer of process technology. Four split and two whole inactivated virus (WIV) influenza vaccine bulks were produced and compared with respect to release criteria, stability of the bulk and haemagglutinin recovery. One clarified harvest of influenza H3N2 A/Uruguay virus prepared on 25.

Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach.

In this study, the effect of liposomal lipid composition on the physicochemical characteristics and adjuvanticity of liposomes was investigated. Using a design of experiments (DoE) approach, peptide-containing liposomes containing various lipids (EPC, DOPE, DOTAP and DC-Chol) and peptide concentrations were formulated. Liposome size and zeta potential were determined for each formulation.

Current and next generation influenza vaccines: Formulation and production strategies.

Vaccination is the most effective method to prevent influenza infection. However, current influenza vaccines have several limitations. Relatively long production times, limited vaccine capacity, moderate efficacy in certain populations and lack of cross-reactivity are important issues that need to be addressed.

Immunoproteomic Profiling of Bordetella pertussis Outer Membrane Vesicle Vaccine Reveals Broad and Balanced Humoral Immunogenicity.

The current resurgence of whooping cough is alarming, and improved pertussis vaccines are thought to offer a solution. Outer membrane vesicle vaccines (omvPV) are potential vaccine candidates, but omvPV-induced humoral responses have not yet been characterized in detail. The purpose of this study was to determine the antigen composition of omvPV and to elucidate the immunogenicity of the individual antigens.

Animal models for cutaneous vaccine delivery.

Main challenges in skin vaccination are overcoming the stratum corneum (SC) barrier and targeting the antigen presenting cells (APC) in the epidermis and the dermis. For this purpose many delivery techniques are being developed. In vivo immunogenicity and safety studies in animals are mandatory before moving to clinical trials.

Influenza T-cell epitope-loaded virosomes adjuvanted with CpG as a potential influenza vaccine.

Purpose: Influenza CD8(+) T-cell epitopes are conserved amongst influenza strains and can be recognized by influenza-specific cytotoxic T-cells (CTLs), which can rapidly clear infected cells. An influenza peptide vaccine that elicits these CTLs would therefore be an alternative to current influenza vaccines, which are not cross-reactive. However, peptide antigens are poorly immunogenic due to lack of delivery to antigen presenting cells, and therefore need additional formulation with a suitable delivery system.

Molecular signatures of the evolving immune response in mice following a Bordetella pertussis infection.

Worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. Since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. The purpose was to elucidate the kinetics of the protective immune response evolving after experimental Bordetella pertussis (B.

Solid bioneedle-delivered influenza vaccines are highly thermostable and induce both humoral and cellular immune responses.

The potential of bioneedles to deliver influenza vaccines was investigated. Four influenza vaccine formulations were screened to determine the optimal formulation for use with bioneedles. The stability of the formulations after freeze-drying was checked to predict the stability of the influenza vaccines in the bioneedles.

Minipigs as an animal model for dermal vaccine delivery.

Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery. Here we describe the immunization of Göttingen minipigs by using intradermal and intramuscular delivery of hepatitis B surface antigen (HBsAg).

Pulmonary vaccine delivery: a realistic approach?

Pulmonary vaccine delivery has gained increasing attention during the last decade because this vaccination method combines potential advantages such as the fact that it omits the use of needles and may elicit immunity at the port of entry for many pathogens. In this review the current status of pulmonary vaccination, the potential advantages of pulmonary vaccine delivery, the hurdles to overcome in the future, and the overall perspectives of this vaccination strategy are described.

Hepatitis B surface antigen nanoparticles coated with chitosan and trimethyl chitosan: Impact of formulation on physicochemical and immunological characteristics.

Mucosal immunization offers various advantages over parenteral vaccination, but typically requires potent delivery systems and/or adjuvants to result in protective immunity. Here we report on the preparation of trimethylated chitosan (TMC) and chitosan (CHT) nanoparticles (NPs) loaded with hepatitis B surface antigen (HB), by a simple and scalable method. TMC:HB and CHT:HB NPs were prepared by direct coating of antigen by polymer.

Towards tailored vaccine delivery: needs, challenges and perspectives.

The ideal vaccine is a simple and stable formulation which can be conveniently administered and provides life-long immunity against a given pathogen. The development of such a vaccine, which should trigger broad and strong B-cell and T-cell responses against antigens of the pathogen in question, is highly dependent on tailored vaccine delivery approaches. This review addresses vaccine delivery in its broadest scope.

Inactivated polio vaccine development for technology transfer using attenuated Sabin poliovirus strains to shift from Salk-IPV to Sabin-IPV.

Industrial-scale inactivated polio vaccine (IPV) production dates back to the 1960s when at the Rijks Instituut voor de Volksgezondheid (RIV) in Bilthoven a process was developed based on micro-carrier technology and primary monkey kidney cells. This technology was freely shared with several pharmaceutical companies and institutes worldwide. In this contribution, the history of one of the first cell-culture based large-scale biological production processes is summarized.

Bioneedles as alternative delivery system for hepatitis B vaccine.

An alternative vaccine delivery system for needle injections is the Bioneedle. Hepatitis B surface antigen (HBsAg) was formulated with Bioneedles. Three formulations were used: plain antigen, HBsAg adjuvated with aluminum hydroxide and HBsAg with LPS-derived lpxL1.

Microneedle-based transcutaneous immunisation in mice with N-trimethyl chitosan adjuvanted diphtheria toxoid formulations.

Purpose: The purpose of this study was to gain insight into the delivery and immunogenicity of N-trimethyl chitosan (TMC) adjuvanted diphtheria toxoid (DT) formulations applied transcutaneously with microneedles.

Methods: Mice were vaccinated with DT-loaded TMC nanoparticles, a solution of TMC and DT (TMC/DT) or DT alone. The formulations were applied onto the skin before or after microneedle treatment with two different 300-microm-long microneedle arrays and also injected intradermally (ID).

Transcutaneous immunization studies in mice using diphtheria toxoid-loaded vesicle formulations and a microneedle array.

Purpose: To determine the immunogenicity of diphtheria toxoid (DT) formulated in two types of vesicles following transcutaneous immunization (TCI) of mice onto microneedle array-treated skin.

Methods: DT-containing cationic liposomes or anionic surfactant-based vesicles were prepared by extrusion and sonication. The physicochemical properties were characterized in terms of size, ζ-potential, vesicle elasticity and antigen association.

Efficient induction of immune responses through intradermal vaccination with N-trimethyl chitosan containing antigen formulations.

The function of N-trimethyl chitosan (TMC) in dermal immunisation is unknown. Therefore we investigated the immunogenicity of both antigen-containing TMC nanoparticles and TMC/antigen solutions after intradermal injection. Nanoparticles were prepared with a size around 200 nm and a positive zetapotential.

Preparation and characterization of diphtheria toxoid-loaded elastic vesicles for transcutaneous immunization.

The objective was to develop surfactant-based vesicle formulations containing diphtheria toxoid (DT) for transcutaneous immunization. Formulation variables were molar ratio of the surfactants (sucrose-laurate ester, octaoxyethylene-laurate ester, and sodium bistridecyl sulfosuccinate), DT concentration, pH, and ionic strength. The formulations were characterized by visual inspection, dynamic light scattering and zeta potential measurements.

Bioneedles as vaccine carriers.

Bioneedles are small hollow mini implants fabricated from biodegradable polymers which can be filled with antigen. Bioneedles can be used for vaccination without syringes and needles. Formulations have been prepared containing tetanus toxoid with and without aluminum phosphate.

Quality control of routine, experimental and real-time aged diphtheria toxoids by in vitro analytical techniques.

Physicochemical and immunochemical techniques can be used to assess the quality of diphtheria toxoid vaccines. In a previous paper [Metz B, Jiskoot W, Hennink WE, Crommelin DJA, Kersten GFA. Physicochemical and immunochemical techniques predict the quality of diphtheria toxoid vaccines.