Combatting infectious diseases: nanotechnology as a platform for rational vaccine design

Drug Delivery Technolog

Outer Membrane Vesicles of Porphyromonas gingivalis Elicit a Mucosal Immune Response

We previously reported that mutation of galE in Porphyromonas gingivalis has pleiotropic effects, including a truncated lipopolysaccharide (LPS) O-antigen and deglycosylation of the outer membrane protein OMP85 homolog. In the present study, further analysis of the galE mutant revealed that it produced little or no outer membrane vesicles (OMVs). Using three mouse antisera raised against whole cells of the P. gingivalis wild type strain, we performed ELISAs to examine the reactivity of these antisera with whole cells of the wild type or the galE mutant. All three antisera had significantly lower reactivity against the galE mutant compared to wild type. OMVs, but not LPS, retained the immunodominant determinant of P. gingivalis, as determined by ELISAs (with wild type LPS or OMVs as antigen) and absorption assays. In addition, we assessed the capacity of OMVs as a vaccine antigen by intranasal immunization to BALB/c mice. Synthetic double-stranded RNA polyriboinosinic polyribocytidylic acid [Poly (I∶C)], an agonist of Toll-like receptor 3 (TLR3), was used as the mucosal adjuvant. Vaccination with OMV elicited dramatically high levels of P. gingivalis-specific IgA in nasal washes and saliva, as well as serum IgG and IgA. In conclusion, the OMVs of P. gingivalis have an important role in mucosal immunogenicity as well as in antigenicity. We propose that P. gingivalis OMV is an intriguing immunogen for development of a periodontal disease vaccine

Pauson-Khand Adducts of N-Boc-propargylamine: A New Approach to 4,5-Disubstituted Cyclopentenones

A new approach to the synthesis of 4,5-disubstituted cyclopentenones is described. The strategy is based on the Pauson-Khand (PK) reaction of norbornadiene and N-Boc-propargylamine as alkyne with a masked leaving group, which can be eliminated at will. This approach to the synthesis of 4,5-disubstituted cyclopentenones overcomes the problem of using the alkylation to introduce the alpha-side-chain. As an example, prostane 13-epi-12-oxo-phytodienoic acid (13-epi-12-oxo-PDA) methyl ester was synthesized

Intranasal inactivated influenza vaccines for the prevention of seasonal influenza epidemics

Introduction: Intranasal influenza vaccines are expected to confer protection among vaccine recipients by successful induction of mucosal immune response in the upper respiratory tract. Though only live attenuated influenza virus vaccines (LAIVs) are licensed and available for intranasal use in humans today, intranasal inactivated influenza vaccines (IIVs) are currently under reconsideration as a promising intranasal influenza vaccine. Areas covered: This review addresses the history of intranasal IIV research and development, along with a summary of the studies done so far to address the mechanism of action of intranasal IIVs. Expert commentary: From numerous in vitro and in vivo studies, it has been shown that intranasal IIVs can protect hosts from a broad spectrum of influenza virus strains. In-depth studies of the mucosal antibody response following intranasal IIV administration have also elucidated the detailed functions of secretory IgA (immunoglobulin A) antibodies which are responsible for the mechanism of action of intranasal vaccines. Safe and effective intranasal IIVs are expected to be an important tool to combat seasonal influenza