Antibodies block Ebola virus entry The recent Ebola virus outbreak in West Africa illustrates the need for both an effective vaccine and therapies to treat infected individuals. Corti et al. isolated two monoclonal antibodies from a survivor of the 1995 Kikwit outbreak and demonstrated their therapeutic efficacy in Ebola virus–infected macaques. In fact, one antibody protected macaques when it was given up to 5 days after infection. Misasi et al. solved the crystal structures of fragments of the two antibodies bound to the Ebola virus glycoprotein (GP), which mediates viral cell entry. The two antibodies targeted different regions of GP, but in both cases blocked steps required for viral entry. Science , this issue pp. 1339 & 1343

Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge.

BackgroundFor most classes of drugs, rapid development of therapeutics to treat emerging infections is challenged by the timelines needed to identify compounds with the desired efficacy, safety, and pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method to overcome many of these hurdles to rapidly produce therapeutics for emerging diseases.MethodsIn this study, we deployed a platform to generate, test, and develop fully human antibodies to Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) antibodies by immunizing VelocImmune mice that use human immunoglobulin variable regions in their humoral responses.ResultsOf the antibody clones isolated, 3 were selected as best at neutralizing EBOV and triggering FcγRIIIa. Binding studies and negative-stain electron microscopy revealed that the 3 selected antibodies bind to non-overlapping epitopes, including a potentially new protective epitope not targeted by other antibody-based treatments. When combined, a single dose of a cocktail of the 3 antibodies protected nonhuman primates (NHPs) from EBOV disease even after disease symptoms were apparent.ConclusionsThis antibody cocktail provides complementary mechanisms of actions, incorporates novel specificities, and demonstrates high-level postexposure protection from lethal EBOV disease in NHPs. It is now undergoing testing in normal healthy volunteers in preparation for potential use in future Ebola epidemics.

A proposed tangential flow ultrafiltration method was compared to the widely used ultracentrifugation method for efficiency and efficacy in concentrating, size selecting, and minimizing the aggregation state of a silver nanoparticle (AgNP) colloid while probing the AgNPs' SERS-based sensing capabilities. The ultrafiltration method proved to be more efficient and more effective and was found to tremendously boost the SERS-based sensing capabilities of these AgNPs through the increased number of homogeneous SERS hot spots available for a biotarget molecule within a minimal focal volume. Future research studies and applications addressing the physiochemical properties or biological impact of AgNPs would greatly benefit from ultrafiltration for its ability to generate monodisperse colloidal nanoparticles, to eliminate excess toxic chemicals from nanoparticle synthesis, and to obtain minimum levels of aggregation during nanoparticle concentration.

A method of fabricating Hill-Downing type, planar thermopiles by vacuum-deposition techniques is described in detail. The present model was designed for initial heat measurements on rabbit papillary muscles as small as 1 mg blotted wt, but it is also suitable for small bundles of frog muscle fibers (30-75). The thermopile has 20 or 14 junctions, an active length of 5 or 3.5 mm, and an actual thickness of 20 micrometer. It has an effective heat capacity of about 0.3 mcal/degrees C, a heat loss coefficient of about 0.3 mcal/degrees C - s, a temperature sensitivity of 1.4 mV/degrees C (20 junctions), and an electrical resistance of 180-200 omega. Infrared-emitting diodes are used to heat the thermopile and muscle artificially for thermal time constant and conduction-delay measurements. Performance of the thermopiles is demonstrated with initial heat records from rabbit right ventricular papillary muscles and a bundle of frog semitendinosus muscle fibers. Results of preliminary experiments concerning latency for heat generation, initial rate of heat generation, and activation heat in both types of muscles are presented.