A respirable HPV-L2 dry-powder vaccine with GLA as amphiphilic lubricant and immune-adjuvant

Vaccines not requiring cold-chain storage/distribution and suitable for needle-free delivery are urgently needed. Pulmonary administration is one of the most promising non-parenteral routes for vaccine delivery. Through a multi-component excipient and spray-drying approach, we engineered highly respirable dry-powder vaccine particles containing a three-fold repeated peptide epitope derived from human papillomavirus (HPV16) minor capsid protein L2 displayed on Pyrococcus furious thioredoxin as antigen. A key feature of our engineering approach was the use of the amphiphilic endotoxin derivative glucopyranosyl lipid A (GLA) as both a coating agent enhancing particle de-aggregation and respirability as well as a built-in immune-adjuvant. Following an extensive characterization of the in vitro aerodynamic performance, lung deposition was verified in vivo by intratracheal administration in mice of a vaccine powder containing a fluorescently labeled derivative of the antigen. This was followed by a short-term immunization study that highlighted the ability of the GLA-adjuvanted vaccine powder to induce an anti-L2 systemic immune response comparable to (or even better than) that of the subcutaneously administered liquid-form vaccine. Despite the very short-term immunization conditions employed for this preliminary vaccination experiment, the intratracheally administered dry-powder, but not the subcutaneously injected liquid-state, vaccine induced consistent HPV neutralizing responses. Overall, the present data provide proof-of-concept validation of a new formulation design to produce a dry-powder vaccine that may be easily transferred to other antigens

seasonal abundance of the nearctic gall midge obolodiplosis robiniae in italy and the impact of its antagonist platygaster robiniae on pest populations

The Nearctic gall midge Obolodiplosis robiniae (Haldeman, 1847) (Diptera Cecidomyiidae) infesting black locusts, Robinia pseudoacacia L. (Fabaceae), was detected in Asia in 2002 and in Europe (first in Italy) in 2003. Its distribution in Europe has expanded dramatically, probably favored by extensive distribution of its host plant along the main routes. The results of a 3-yr study on the seasonal abundance of O. robiniae in northern Italy are reported here. O. robiniae can develop three to four generations per year by exploiting plants of different ages and vigor. Overwintering takes place as diapausing larvae and adults emerge in spring. Two generations are completed on mature plants where populations decline in summer. Two additional generations can develop on root suckers from midsummer onward. Pest population densities reach their highest levels in late spring. Gall midge larvae were attacked by various predators, but parasitism by the platygastrid Platygaster robiniae Buhl & Duso was particularly significant. The impact of parasitism by P. robiniae is indicated as a key factor in reducing O. robiniae population densities

Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions

Bifidobacteria represent one of the dominant groups of microorganisms colonizing the human infant intestine. Commensal bacteria that interact with a eukaryotic host are believed to express adhesive molecules on their cell surface that bind to specific host cell receptors or soluble macromolecules. Whole-genome transcription profiling of Bifidobacterium bifidum PRL2010, a strain isolated from infant stool, revealed a small number of commonly expressed extracellular proteins, among which were genes that specify sortase-dependent pili. Expression of the coding sequences of these B. bifidum PRL2010 appendages in nonpiliated Lactococcus lactis enhanced adherence to human enterocytes through extracellular matrix protein and bacterial aggregation. Furthermore, such piliated L. lactis cells evoked a higher TNF-α response during murine colonization compared with their nonpiliated parent, suggesting that bifidobacterial sortase-dependent pili not only contribute to adherence but also display immunomodulatory activity

Role of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in modulating bacterium-host interactions

Bifidobacteria represent one of the dominant groups of microorganisms colonizing the human infant intestine. Commensal bacteria that interact with a eukaryotic host are believed to express adhesive molecules on their cell surface that bind to specific host cell receptors or soluble macromolecules. Whole-genome transcription profiling of Bifidobacterium bifidum PRL2010, a strain isolated from infant stool, revealed a small number of commonly expressed extracellular proteins, among which were genes that specify sortase-dependent pili. Expression of the coding sequences of these B. bifidum PRL2010 appendages in nonpiliated Lactococcus lactis enhanced adherence to human enterocytes through extracellular matrix protein and bacterial aggregation. Furthermore, such piliated L. lactis cells evoked a higher TNF-\u3b1 response during murine colonization compared with their nonpiliated parent, suggesting that bifidobacterial sortase-dependent pili not only contribute to adherence but also display immunomodulatory activity

La costruzione di una mappa di sostenibilità ambientale a Milano: le condizioni di rischio ed opportunità

pubblicazione Ufficio Studi CCIAA Milan