EVOLUTION: Of Mice . . .

Background Approximately 20 percent of adults become infected with human papillomavirus type 16 (HPV-16). Although most infections are benign, some progress to anogenital cancer. A vaccine that reduces the incidence of HPV-16 infection may provide important public health benefits. Methods In this double-blind study, we randomly assigned 2392 young women (defined as females 16 to 23 years of age) to receive three doses of placebo or HPV-16 virus-like–particle vaccine (40 μg per dose), given at day 0, month 2, and month 6. Genital samples to test for HPV-16 DNA were obtained at enrollment, one month after the third vaccination, and every six months thereafter. Women were referred for colposcopy according to a protocol. Biopsy tissue was evaluated for cervical intraepithelial neoplasia and analyzed for HPV-16 DNA with use of the polymerase chain reaction. The primary end point was persistent HPV-16 infection, defined as the detection of HPV-16 DNA in samples obtained at two or more visits. The primary analys...

A controlled trial of a human papillomavirus type 16 vaccine.

Innate immunity: impact on the adaptive immune response

A surgical clip applier includes a housing, a pair of handles pivotably connected to opposite sides of the housing, a channel assembly which is anchored to the housing and a jaw assembly which is anchored to the channel assembly. The jaws are opened and closed by a cam plate which is slidably positioned in the channel assembly and is provided with cam slots at its distal end to engage drive rivets positioned on the jaw members. A pusher bar assembly is also provided to feed clips from a series of clips to the jaw mechanism, and the instrument operates such that all moving components move in the same direction during the closing stroke of the handle, and then move in the same direction opposite to the closing direction when the handles are in the opening stroke. A novel lockout mechanism is also provided to render the instrument inoperable after all the clips have been utilized from the instrument.

Surgical clip applier

Recent advances in wet chemical synthesis and biomolecular functionalization of gold nanoparticles have led to a dramatic expansion of their potential biomedical applications, including biosensorics, bioimaging, photothermal therapy, and targeted drug delivery. As the range of gold nanoparticle types and their applications continues to increase, human safety concerns are gaining attention, which makes it necessary to better understand the potential toxicity hazards of these novel materials. Whereas about 80 reports on the in vivo biodistribution and in vitrocell toxicity of gold nanoparticles are available in the literature, there is lack of correlation between both fields and there is no clear understanding of intrinsic nanoparticle effects. At present, the major obstacle is the significant discrepancy in experimental conditions under which biodistribution and toxicity effects have been evaluated. This critical review presents a detailed analysis of data on the in vitro and in vivo biodistribution and toxicity of most popular gold nanoparticles, including atomic clusters and colloidal particles of diameters from 1 to 200 nm, gold nanoshells, nanorods, and nanowires. Emphasis is placed on the systematization of data over particle types and parameters, particle surface functionalization, animal and cell models, organs examined, doses applied, the type of particle administration and the time of examination, assays for evaluating gold particle toxicity, and methods for determining the gold concentration in organs and distribution of particles over cells. On the basis of a critical analysis of data, we arrive at some general conclusions on key nanoparticle parameters, methods of particle surface modification, and doses administered that determine the type and kinetics of biodistribution and toxicity at cellular and organismal levels (197 references).

Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies

Immunogeni di proteine che legano il fattore h.

Developing deoxyribonucleic acid (DNA) vaccines potent enough to be clinically useful will likely require an understanding of the mechanism of action both of naked DNA vaccines themselves, and of adjuvant formulations that may be combined with DNA. Mechanisms of action attributed to naked DNA vaccines described thus far include transfection of keratinocytes (1), muscle cells (2), and dendritic cells (DCs) (3), and activation of innate immunity by pathogen- associated molecular patterns (PAMPs) such as unmethylated CpG-containing immunostimulatory sequences (4). Improving the immunogenicity of DNA vaccines has focused on four areas of investigation: increasing stability and efficiency of transfection, maximizing the ability of the antigen to be presented by DCs, and stimulating the immune response to the target antigen. A collective body of work demonstrating the versatility and mechanism of action of microparticle/DNA vaccine formulations supports promise of developing effective DNA vaccines utilizing this potent adjuvant/delivery system. Understanding the mechanism of action of DNA/microparticles provides both a basis for rational optimization of the formulation and basic insights into efficient induction of immunity.

Microparticles and DNA Vaccines

Hiv-vakzine-formulierungen

Immunogenische Zusammensetzung einer Spikeprotein des SARS Coronavirus

L'invention porte sur des microparticules presentant des surfaces absorbantes, et sur des methodes de production et d'utilisation desdites microparticules. Les microparticules de l'invention comprennent un polymere, tel qu'un poly(α-hydroxyacide), un acide butyrique polyhydroxyle, un polycaprolactone, un polyorthoester, un polyanhydride et analogue, et sont formees avec des detergents cationiques, anioniques ou non anioniques. L'invention concerne egalement des microparticules sous forme d'emulsions submicroniques d'une emulsion de globules d'huile comportant une huile metabolisee et un agent dispersant. La surface des microparticules adsorbe efficacement des polypeptides tels que des antigenes, et des acides nucleiques tels que des vecteurs ELVIS ou autres constructions vecteurs contenant des sequences nucleotidiques heterologues codant des macromolecules biologiquement actives, telles que des polypeptides, des antigenes et des adjuvants. L'invention porte en outre sur des methodes de stimulation d'une reponse immune et sur des methodes d'immunisation d'un animal hote contre une infection virale, bacterienne ou parasitaire. Elle porte enfin sur l'utilisation des compositions microparticulaires de l'invention dans des vaccins.

John J. Donnelly

Papers

Immunogeni di proteine che legano il fattore h.

Microparticles and DNA Vaccines

Hiv-vakzine-formulierungen

Immunogenische Zusammensetzung einer Spikeprotein des SARS Coronavirus

Microparticules de transport d'acides nucleiques heterologues