AEROSOLTERAPIA BELLICA: VACCINI ANCHE DAL CIELO

di Gianni Lannes

La fantascienza ha superato di gran lunga la realtà, mentre la stragrande maggioranza della popolazione mondiale viene mantenuta nell'ignoranza. I criminali in camice bianco e divisa militare a mano armata non chiedono mai il consenso informato ai pazienti, ma li trattano come cavie. Ecco la follia scientifica all’opera. Un nuovo sistema di vaccini  particolarmente attivi nel sistema respiratorio, attraverso la dispersione di nanoparticelle nell’aria. Infatti, il dottor David Edwards della Harvard University, nel Massachusetts (U.S.A.), guida una squadra multidisciplinare di ricercatori che utilizza tecnologie per sviluppare una linea colturale di cullule BCG per il vaccino anti-tubercolosi e l’antigene proteina CRM197 da destinare al vaccino anti-difterico sotto forma di nuove nanoparticelle da somministrare, appunto via aerosol dall’alto dei cieli.

http://www.grandchallenges.org/ImproveVaccines/Challenges/NeedleFreeDelivery/Pages/Aerosols.aspx

PRIMARY INVESTIGATOR: Dr. David Edwards, Harvard University/Medicine in Need, Massachusetts, United States - US Needle Free Vaccination Via Nanoparticle Aerosols

Most childhood vaccines are delivered through injection. This increases the risk that HIV, hepatitis, and other serious diseases might be transmitted by unsterile syringes and needles.  Moreover, injecting vaccines can be a complex process, and used syringes and needles create a major waste disposal problem. Vaccine delivery systems that target specific areas of the body have the potential to be simpler and less prone to risk of infection, as well as especially effective against some types of infection. For example, inhaled vaccines may better guard against respiratory diseases, such as tuberculosis, and those that commonly infect the tissues of the nose and throat, such as diphtheria. Dr. Edwards is leading a multidisciplinary team using materials science technologies combined with infectious disease, device, and toxicology expertise to reformulate tuberculosis and diphtheria vaccines into aerosol sprays that can be inhaled. The team's ultimate objective is to develop a cell-based BCG vaccine for tuberculosis and a protein antigen CRM 197 vaccine for diphtheria in the form of novel porous nanoparticle aggregate (PNAP) aerosols. Investigators are working toward the possibility of clinical development of an inhaled BCG product candidate. Supported by a supplemental grant and working with the nonprofit organization Medicine in Need (MEND), the project team has developed infrastructure in South Africa to prepare inhaled BCG toxicology material. They have also identified a clinical manufacturing option with Advanced BioScience Laboratories, Inc. (ABL) of Maryland.

Research Objectives: Prepare chemically and physically stable PNAPs economically and in a scaleable fashion, using vaccine candidates that range from protein to attenuated whole bacteria. Investigators intend to show that their process of spray drying can produce dry vaccine powders with at least the cost efficiency of freeze drying, and can produce substantially purer active vaccine substance for delivery. Deliver via PNAP formulations large masses of antigen to the bronchopulmonary mucosa of infants and adults. Investigators intend to show that by formulating vaccines in PNAP aerosols, up to 100 mg of vaccine can be delivered to the pulmonary mucosa in several breaths, requiring less than a minute. Engineer the size and composition of nanoparticles in PNAP aerosols to enhance targeting of vaccine to dendritic cells and macrophages in the respiratory tract. By formulating vaccines into nanoparticles in the size range of 50-300 nanometers, investigators aim to show that vaccines can be specially targeted to these cells for more effective vaccination per dose. Deliver vaccine to the lungs to provide an enhanced pulmonary and systemic immunity relative to intradermal injection

Project Progress & Milestones: Demonstrated the capability of spray drying live non-replicating bacteria dry vaccine powders at potentially low cost and large scale. The team has published results (PNAS 2007 104(8):2591-2595) that show by drying bacteria such as BCG in salt-free suspensions, osmotic stresses can be minimized during drying and good activity and shelf-life stability achieved. Work with CRM 197 has led to a scaleable method for PNAP production, but animal studies suggest the team has not yet achieved active CRM 197 in the PNAP powders. Demonstrated excellent aerosol properties for BCG and CRM biomaterial forms that can lead to delivery of up to 100 mg of vaccine powder to the pulmonary mucosa of infants and adults in several breaths, requiring less than a minute. BCG work shows that the excellent aerosol properties of dry BCG are related to a new biomaterial “nanomicroparticle” form that differs from that described in the team's initial PNAP proposal; These aerosols possess two axes of nanoscale dimensions and a third axis of micron dimension. The latter permits effective physical dispersion and the former, alignment of the principal nano-dimension particle axes with the direction of airflow. Investigators also have developed a novel patented newborn delivery system that works effectively with their new biomaterial vaccines. Engineered size and composition of nanoparticles in PNAP aerosols to target cells of the respiratory tract. Investigators have formulated PNAP carriers with 100 nm and 200 nm nanoparticles and found in preliminary fate-mapping studies in rats that 100 nm particles are taken up more preferrentially than are 200 nm particles. Demonstrated that the nanomicroparticle formulations of BCG produce heightened immunity compared to intradermal and subcutaneous injections. The team's study in a TB-infection guinea pig model suggests that equal body dosing of BCG by the pulmonary route produces statistically more significant reduction in colony forming units relative to intradermal and subcutaneous injection both locally (in the lung) and systemically (in the spleen).

Publications and Related Links: Wong ,Y et al., Proceedings of the National Academy of Sciences, 104, 2591-2595, 2007

Collaborators: Aeras Foundation, Maryland, United States - US Biovac Institute, Cape Town, South Africa - ZA Dr. Peter Andersen, Statens Serum Institute, Copenhaugen, Denmark - DK Dr Maria J Alonso, University of Santiago de Compostela, Santiago de Compostela, Spain - ES James Baker, Michigan, United States - US Stefan Kaufmann, Berlin, Germany - DE Peter Singer, Canada - CA http://www.pnas.org/content/104/8/2591.full.pdf+html