Low expression, poor solubility, and polyspecificity are significant obstacles that have impeded the development of antibodies discovered from in vitro display libraries. Current biophysical characterization tools that identify these 'developability' problems are typically only applied after the discovery process, and thus limited to perhaps a few hundred candidates. We report a flow cytometric assay using a polyspecificity reagent (PSR) that allows for the identification and counter selection of polyspecific antibodies both during and after the selection process. The reported assay correlates well with cross-interaction chromatography, a surrogate for antibody solubility, as well as a baculovirus particle enzyme-linked immunosorbent assay, a surrogate for in vivo clearance. However, unlike these assays, PSR labeling is compatible both with screening of individual antibodies as well as selections of large antibody libraries. To this end, we demonstrate the ability to counter-select against polyspecificity while enriching for antigen affinity from a diverse antibody library, which enables simultaneous evolution of both antigen binding and superior non-target-related properties during the discovery process.

The influence of preformed, anti-whole organism antibody on the development of Streptococcus sanguis endocarditis was examined in both in vivo and in vitro systems. Antibody prevented, rather than potentiated, endocarditis in rabbits. The infectious dose in 30 control animals was 10(6.5) +/- 0.33 (mean +/- standard deviation); this increased to 10(7.71 +/- 0.05 in 36 immunized animals (P less than 0.01). No differences in bacterial clearance mechanisms were apparent between groups. Antibody also prevented the adherence of S. sanguis to the constituents of nonbacterial thrombotic endocarditis (fibrin and platelets) in vitro. When preincubated in high-titer antisera, adherence of S. sanguis was reduced compared with controls (adherence ratio mean +/- standard error of the mean, X 10(4): 174 +/- 5 versus 427 +/- 10, P less than 0.001). Preadsorption of immune sera with intact S. sanguis restored adherence to normal values, whereas preadsorption with dextran was partially effective. These studies demonstrate that preformed antibody had a protective role in vivo and suggest that a possible mechanism is blockade of adherence, a crucial early step in the pathogenesis of endocarditis.

Summary Background On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain. Methods We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage. Findings 28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217. Interpretation This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt.

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263aecatriz. He, on the other hand, always found t h a t it was difficult to ensure that poultry developed a n p firm immunity to intestinal coccidiosis. n referring to Dr. Albiston's remarks on the predisposing causes of caecal coccidiosis, he said that, though they were important, experimentally it was possible to produce coccidiosis in chicks kept under warm conditions and on a good ration.H e said that, in his experience, where birds are kept on litter, it is a good practice to provide fresh litter for each new batch of chicks, but to incor orate in this a small quantity of contaminatecflitter. This will provide a source of coccidial infection which will stimulate immunity while the birds a r e being given a medicated mash.Nitrofurazone is a drug which gives considerably better results under field conditions than one would expect from its laboratory performance.A . K . Sutherland (Vic.) said that there was a luck in knowledge of the factors that give rise to outbreaks of coccidiosis. If there had been an increase in the incidence of coccidiosis i n spite of the availability of efficient drugs, this may have been associated with the increased use of battery brooders which would result usually in the chickens being unexposed to oocysts and so not developing any immunity before they were transferred to floor pens at four weeks of age.Formerly floor brooding was much more widely used, usually exposing chickens to small doses of oocysts from a n early age. (Vic.), in answering Mr. Brander, asked whether he had typed the infections referred to, as he thought that many of them may have been due to E. aceniulina. He agreed t h a t management was a n important factor but considered t h a t on old farms, or where conditions were bad, drugs were essential. Therefore a balance must be struck between management and drugs. J . H . Arundel