Biomedical subjects

Vincent W Bramwell

Publications and source records attributed to Vincent W Bramwell.

11 recordsLinked to original sources

PubMed2006

Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems.

Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

Administration, Intranasal↗

PubMed2006

Lyophilisation and sterilisation of liposomal vaccines to produce stable and sterile products.

The advantages of liposomes as delivery systems for peptide, protein and DNA vaccines is well-recognised, unfortunately their application has been stinted by their instability during storage and their limited shelf-life. Further, sterilisation of these systems has been problematic, with degradation of the liposomes being reported after sterilisation using the various techniques available. Work form our laboratory has investigated techniques that can be applied to particulate liposomal vaccines such that they can be prepared in a freeze-dried and sterile format. In this article, we describe techniques for the lyophilisation, cryoprotection and sterilisation of liposomal vaccines. Applying these methods allows for the retention of both the chemical integrity of the lipids and the key physico-chemical characteristics of the liposomes (e.g., particle size, zeta potential, and dynamic viscosity), thus supporting the enhanced transition of liposomal vaccines from the bench to the clinic.

Adjuvants, Immunologic↗

PubMed2006

Particulate delivery systems for vaccines: what can we expect?

In our attempts to thwart the unwanted attentions of microbes by prophylactic and therapeutic vaccination, the knowledge of interactions at the molecular level may prove to be an invaluable asset. This article examines how particulate delivery systems such as liposomes and polymer microspheres can be applied in the light of recent advances in immunological understanding. Some of the biological interactions of these delivery systems are discussed with relevance for antigen trafficking and molecular pathways of immunogenicity and emphasis on the possible interaction of liposomal components. In particular, traditional concepts such as antigen protection, delivery to antigen presenting cells and depot formation remain important aspects, whilst the inclusion of selected co-adjuvants and enhanced delivery of these moieties in conjunction with antigen now has a firm rationale.

Adjuvants, Immunologic↗

PubMed2005

The rational design of vaccines.

This review provides an insight into the various opportunities for vaccine intervention, analysis of strategies for vaccine development, vaccine ability to modulate immune responses and resultant rational vaccine design. In addition, wider aspects are considered, such as biotechnological advances, advances in immunological understanding and host-pathogen interactions. The key question addressed here is, with all our research and understanding, have we reached a new echelon in vaccine development, that of rational design?

Drug Delivery Systems↗

PubMed2005

Modulating the adjuvanticity of alum by co-administration of muramyl di-peptide (MDP) or Quil-A.

The characterization of the immunological cascades of the innate immune system activated by pathogen associated molecular patterns (PAMP) recognized by pattern recognition receptors (PRR) have allowed the elucidation of the mechanisms underlying the immunomodulatory properties of adjuvants. Thus, the combinatorial use of adjuvants with specific, complementary functions is investigated to achieve tailored immune responses to subunit vaccines. We have previously shown how combinatorial administration of chitosan and cholera toxin B or muramyl-di-peptide (MDP) intranasally, but not intramuscularly, can allow small doses of MDP which, when administered alone cannot adjuvantise Helicobacter pylori urease (rUre), achieve an immunomodulatory effect through the specific physiological effect of chitosan. The aim of this study was to investigate if in the context of rUre the adjuvantising effect of MDP could be realized via the intramuscular route by combination with aluminium hydroxide, as compared with the routinely used veterinary adjuvant combination of alum and Quil-A. Serum IgG kinetics were comparable between the two adjuvant combination groups. However, the alum + MDP combination afforded higher antigen-specific recall responses in splenocyte cultures, associated with elevated release of the type I immune response cytokines IFN-gamma and IL-2. This data suggests that the adjuvanticity of MDP can be modulated in the context of alum in a manner dissimilar to that of Quil-A, achieving a balancing effect on the responses elicited by alum adjuvantisation.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2005

Particulate delivery systems for biodefense subunit vaccines.

Expanding identification of potentially protective subunit antigens and correlates of protection has provided a basis for the introduction of safer vaccines. Despite encouraging results in animal models, the significant potential of particulate delivery systems in vaccine design has not yet translated into effective vaccines available for use in humans. This review article will focus on the current status of the development of particulate vaccines, mainly liposomes and bio-degradable polymers, against potential agents for biowarfare: plague, anthrax, botulinum, and smallpox; and filoviruses: Marburg and Ebola.

Animals↗

PubMed2005

Comparative immunomodulatory properties of a chitosan-MDP adjuvant combination following intranasal or intramuscular immunisation.

As the precise functions of adjuvants become clearer, opportunities are presented in their complementary use for the induction of tailored immune responses to subunit vaccines. Here we comparatively investigate the immunological outcome following intranasal or intramuscular immunisation with Helicobacter pylori urease admixed to a chitosan and muramyl di-peptide (MDP) combination. MDP appeared to limit the antigenicity of rUre by either administration route. Nasal administration of the combined adjuvant formulation resulted in an up-regulation of type I recall responses in splenocytes as opposed to adjuvantisation with chitosan alone. In contrast, intramuscular immunisation appeared to limit the responsiveness to the antigen when adjuvanted with chitosan and even more so when chitosan was combined with MDP, suggesting that the mechanism of adjuvantisation and adjuvant synergy differed depending on the immunisation route. Recognising the benefit of improved delivery of MDP intranasally due to the specific physiological effects of chitosan, we discuss the impact of the newly identified pathogen associated molecular pattern (PAMP) role of MDP with respect to the adjuvanticity of proposed chemical variants of this peptide adjuvant.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2005

Strategies for DNA vaccine delivery.

Strategies for gene delivery comprise a diverse range of live and synthetic approaches; DNA delivery for the purposes of immunisation in turn comprises a large part of this research. This review mainly discusses synthetic systems for application in the delivery of plasmid DNA vaccines, outlining polylactide-co-glycolide, liposome, chitosan and complex combination delivery systems. Areas of promise for DNA vaccine candidates include immune modulation of allergic responses and veterinarian application. The potential for realistic consideration of DNA vaccines as an alternative to existing approaches is dependent on the development of efficient DNA vaccine vectors and improved systems for DNA vaccine delivery. DNA vaccine technology may yet prove to be an important asset in an environment where there is a critical need for therapeutic and prophylactic strategies to combat a wide range of disease states.

Animals↗

PubMed2005

Particulate delivery systems for vaccines.

This review focuses on the use of particulate delivery systems for the purposes of immunization. This includes poly(lactide-co-glycolide) (PLGA), ISCOMs, liposomes, niosomes, virosomes, chitosan, and other biodegradable polymers. These systems are evaluated in terms of their use as carriers for protein subunit and DNA vaccines. There is an extensive focus on recent literature, the understanding of biological interactions, and relation of this to our present understanding of immunological mechanisms of action. In addition, there is consideration of formulation techniques including emulsification, solvent diffusion, DNA complexation, and entrapment. The diversity of formulation strategies presented is a testament to the exponential growth and interest in the area of vaccine delivery systems. A case study for the application of particulate vaccine carriers is assessed in terms of vaccine development and recent insights into the possible design and application of vaccines against two of the most important pathogens that threaten mankind and for which there is a significant need: Mycobacterium tuberculosis and human immunodeficiency virus. This review addresses the rationale for the use of particulate delivery systems in vaccine design in the context of the diversity of carriers for DNA- and protein-based vaccines and their potential for application in terms of the critical need for effective vaccines.

Drug Delivery Systems↗

PubMed2002

Liposome/DNA complexes coated with biodegradable PLA improve immune responses to plasmid encoding hepatitis B surface antigen.

We hypothesized that the addition of polymer to the surface of liposome/DNA complexes may potentially enhance in vivo delivery of plasmid DNA to antigen-presenting cells and thereby facilitate enhanced immune responses to encoded protein. BALB/c mice were immunized subcutaneously or intramuscularly three times with a total of 50 microg of the plasmid pRc/CMV-HBs(S) (ayw subtype) encoding for the hepatitis B surface antigen. We measured transgene-specific total immunoglobulin G (IgG), IgG2a, IgG2b and IgG1 antibody responses as well as splenocyte and T-cell proliferation and cytokine production upon re-stimulation following immunization. Modification of lipid/DNA complexes by the polymer precipitation method used here for the addition of poly(d,l-lactic acid) was found to be consistently and significantly more effective than either unmodified liposomal DNA or naked DNA in eliciting transgene-specific immune responses to plasmid-encoded antigen when administered by the subcutaneous route. In addition, the polymer-modified formulations delivered by this route were more effective than naked DNA delivered by the intramuscular route in inducing antibody responses (n=5, P<0.03). Our observations provide 'proof of principle' for the use of these multicomponent formulations, which offer potential for manipulation and increased transfection efficiency in vivo for the purposes of genetic immunization.

Animals↗

PubMed2002

Current status of DNA vaccines and their route of administration.

This review is aimed at bringing DNA vaccines into perspective with regard to other currently available vaccines and vaccine strategies in development. It is concluded that, encouragingly, DNA vaccines still offer significant potential, with more recent developments such as improved vectors and delivery systems likely to have an important impact; and in addition, the potential safety of DNA as a vaccine is becoming increasingly apparent. Strategies for oral delivery may be suitable for some applications, with all nonparenteral routes likely to require suitable carriers or adjuvants. The diversity of experimental data attests to the increasing interest in vaccination for the treatment and prevention of disease.

Adjuvants, Immunologic↗