Vaccines based on outer membrane vesicles (OMV) were developed more than 20 years ago against Neisseria meningitidis serogroup B. These nano-sized structures exhibit remarkable potential for immunomodulation of immune responses and delivery of “self” meningococcal antigens or unrelated antigens incorporated into the vesicle structure. This paper reviews different applications in OMV Research and Development (R&D) and provides examples of OMV developed and evaluated at the Finlay Institute in Cuba. A Good Manufacturing Practice (GMP) process was developed at the Finlay Institute to produce OMV from N. meningitidis serogroup B (dOMVB) using detergent extraction. Subsequently, OMV from N. meningitidis, serogroup A (dOMVA), serogroup W (dOMVW) and serogroup X (dOMVX) were obtained using this process. More recently, the extraction process has also been applied effectively for obtaining OMV on a research scale from Vibrio cholerae (dOMVC), Bordetella pertussis (dOMVBP), Mycobacterium smegmatis (dOMVSM) and BCG (dOMVBCG). The immunogenicity of the OMV have been evaluated for specific antibody induction, and together with functional bactericidal and challenge assays in mice have shown their protective potential. dOMVB has been evaluated with non-self neisserial antigens, including with a herpes virus type 2 glycoprotein, ovalbumin and allergens. In conclusion, OMV are proving to be more versatile than first conceived and remain an important technology for development of vaccine candidates.

Background and purpose: In this study we examined the effect of the natural product cardamonin, upon lipopolysaccharide (LPS)‐induced inflammatory gene expression in order to attempt to pinpoint the mechanism of action.Experimental approaches: Cardamonin was isolated from the Greek plantA. absinthiumL. Its effects were assessed on LPS‐induced nitrite release and iNOS and COX‐2 protein expression in two macrophage cell lines. Western blotting was used to investigate its effects on phosphorylation of the mitogen activated protein (MAP) kinases, ERK, JNK and p38 MAP kinase, and activation of the NFκB pathway, at the level of IκBαdegradation and phosphorylation of NFκB. Also its effects on NFκB and GAS/GAF‐DNA binding were assessed by EMSA.Key results: Cardamonin concentration‐dependently inhibited both NO release and iNOS expression but had no effect on COX‐2 expression. It did not affect phosphorylation of the MAP kinases, degradation of IκBαor phosphorylation of NFκB. However, it inhibited NFκB DNA‐binding in both LPS‐stimulated cells and nuclear extracts of the cells (in vitro). It also inhibited IFNγ‐stimulated iNOS induction and GAS/GAF‐DNA binding.Conclusions and Implications: These results show that the inhibitory effect of cardamonin on LPS‐induced iNOS induction is not mediated via effects on the initial activation of the NFκB or MAP kinase pathways but is due to a direct effect on transcription factor binding to DNA. However, although some selectivity in cardamonin's action is implicated by its inability to affect COX‐2 expression, its exact mechanism(s) of action has yet to be identified.British Journal of Pharmacology(2006)149, 188–198. doi:10.1038/sj.bjp.0706856

Due to the increasing problem of drug resistance, new and improved medicines are required. Natural products and biotherapeutics offer a vast resource for new drugs; however, challenges, including the cost and time taken for traditional drug discovery processes and the subsequent lack of investment from the pharmaceutical industry, are associated with these areas. New techniques are producing compounds with appropriate activity at a faster rate. While the formulation of these combined with drug-delivery systems offers a promising approach for expanding the drug developments available to modern medicine. Here, various classes of drug-delivery systems are described and the advantages they bring to small molecule and biotherapeutic targeting are highlighted. This is an attractive approach to the pharmaceutical industry and the rising trend in research in this area is examined in brief. [Formula: see text].