Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer

Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g. proteins). As a result they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Comparing microbiotas in the upper aerodigestive and lower respiratory tracts of lambs

Abstract Background Recently, the importance of the lung microbiota during health and disease has been examined in humans and in small animal models. Whilst sheep have been proposed as an appropriate large animal model for studying the pathophysiology of a number of important human respiratory diseases, it is clearly important to continually define the limits of agreement between these systems as new concepts emerge. In humans, it has recently been established that the lung microbiota is seeded by microbes from the oral cavity. We sought to determine whether the same was true in sheep. Results We took lung fluid and upper aerodigestive tract (oropharyngeal) swab samples from 40 lambs (7 weeks old). DNA extraction was performed, and the V2-V3 region of the 16S rRNA gene was amplified by PCR then sequenced via Illumina Miseq. Oropharyngeal swabs were either dominated by bacteria commonly associated with the rumen or by bacteria commonly associated with the upper aerodigestive tract. Lung microbiota samples did not resemble either the upper aerodigestive tract samples or reagent-only controls. Some rumen-associated bacteria were found in lung fluids, indicating that inhalation of ruminal bacteria does occur. We also identified several bacteria which were significantly more abundant in lung fluids than in the upper aerodigestive tract swabs, the most predominant of which was classified as Staphylococcus equorum. Conclusions In contrast to humans, we found that the lung microbiota of lambs is dissimilar to that of the upper aerodigestive tract, and we suggest that this may be related to physiological and anatomical differences between sheep and humans. Understanding the comparative physiology and anatomy underlying differences in lung microbiota between species will provide a foundation upon which to interpret changes associated with disease and/or environment