The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose.

A potentially deadly A/H7N9 avian-origin influenza virus is currently the cause of an ongoing outbreak in China. Preparedness plans have thus been initiated to preempt the spread of this virus, which appears to have substantial pandemic potential. To effectively prevent a pandemic from unfolding, rapid production of an immunogenic vaccine with an acceptable safety profile is critical. Given the significance to public health, we are reporting immunogenicity and safety results from a phase 1 study in healthy adults administered one of four inactivated A/H7N9 vaccine formulations. Three formulations contained increasing quantities of antigen and of an oil-in-water adjuvant, MF59, and one formulation contained only the maximum dose of antigen without adjuvant. All vaccine formulations were derived using a synthetic virus seed technology in combination with a cell culture approach; together, these techniques have been shown to expedite vaccine production compared to conventional methods. Higher responses were seen with the MF59-adjuvanted versus the nonadjuvanted A/H7N9 vaccine, with significant and potentially protective immune responses after two doses in most subjects with no preexisting immunity to the H7N9 virus. Further, despite increased injection site pain and other mild effects with MF59, all formulations were well tolerated. These encouraging immunogenicity and safety data on the A/H7N9 vaccine provide a strong rationale for further clinical development. By also using synthetic seed/cell culture technology, we are now one step closer to being able to rapidly and reliably respond to a potential H7N9 pandemic using a clinically tested A/H7N9 vaccine.

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Background and objectives: Staphylococcus aureus is a leading cause of infection in patients with ESRD. Clinical and economic outcomes associated with S. aureus bacteremia and other S. aureus infections in patients with ESRD were examined.Design, setting, participants, & measurements: Laboratory, clinical, and hospital billing data from a randomized trial of 3359 hemodialysis-dependent patients hospitalized with S. aureus infection in the United States whose vascular access type was fistula or graft and who were hospitalized with S. aureus infection to evaluate inpatient costs, hospital days, and mortality over 12 wk were used. Generalized linear regression was used to identify independent predictors of 12-wk costs, inpatient days, and mortality.Results: Of the 279 patients (8.3%) who developed S. aureus infection during approximately 1 yr of follow-up, 25.4% were treated as outpatients. Among patients for whom billing data were available, 89 patients hospitalized with S. aureus bacteremia incurred mean 12-wk inpatient costs of $19,454 and 11.9 inpatient days. Among the 70 patients hospitalized with non-bloodstream S. aureus infections, mean inpatient costs were $19,222 and the mean number of inpatient days was 11.3. Twelve-week mortality was 20.2 and 15.7% for patients with S. aureus bloodstream and non-bloodstream infections, respectively. Older age was independently associated with higher risk of death among patients with S. aureus bacteremia and with higher inpatient costs and more hospital days among patients with non-bloodstream infections.Conclusions: Hemodialysis-dependent patients with fistula or graft access incur high costs and long inpatient stays when hospitalized for S. aureus infection.

Immunochemical and immunocytochemical techniques have been used to identify and characterize glucagon-related peptides of the rat central nervous system. These peptides show immunoreactivity with antiglucagon sera directed towards the central portion of the hormone, but not with antisera specific for the free COOH terminus of glucagon. Highest concentrations were found in hypothalamus (6.1 i 1.6 ng/g wet weight) although lower amounts (approximately 2 ng/g) were found in cortex, thalamus, cerebellum, and brain stem. During recent years, a number of intestinal peptides, including substance P (1, 2), vasoactive intestinal peptide (3, 4), and cholecystokinin (5-7), have been identified within the mammnalian brain. Immunoreactive and biologically active pancreatic insulin has also been identified in central nervous tissue of the rat and has been localized, in part, to cells in the olfactory lobe and hypothalamus (8). Conversely, somatostatin (9) and thyrotropin-releasing hormone (10), peptides originally identified in the hypothalamus, have now been found in pancreatic islets. Although in many cases the anatomical diversity of these peptides has yet to be explained functionally, these findings emphasize a close relationship among peptides of the nervous system and those of the pancreas and gastrointestinal tract. Peptides related to pancreatic glucagon occur in several tissues of the body and represent an unusual group of proteolytically modified forms: although gastric glucagon appears to be identical to the 29-residue hormone isolated from pancreas (11), intestinal glucagon-like peptides have higher molecular weights and contain the structure of the hormone extended from its NH2 and COOH termini (12-16). By structural (14, 15), immunocytochemical (16), and biosynthetic (17, 18) criteria, it appears that these larger peptides represent incompletely processed forms of proglucagon. The mapping of biological tissues for these glucagon-containing peptides thus permits an assessment of selective posttranslational modificationThe publication costs of this article were defyayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 6229as well as an examination of specific gene expression or cellular uptake. This report describes the identification and localization of higher molecular weight forms of glucagon within the brain of the rat. These peptides, like their intestinal counterparts, appear to have both NH2-terminal and COOH-terminal extensions on the glucagon sequence and probably result from a limited posttranslational modification of the glucagon ptcursor. While this work was in progress, two short reports on the subject appeared (19,20). MATERIALS AND METHODSAntisera and Radioimmunoassays. Three antisera directed against pancreatic glucagon were used in the studies reported here. Antiserum NS (15, 21) is a low-titer serum prepared in a chicken by using a glucagon-albumin conjugate. It reacts well with ...

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Background A/H5N1 influenza viruses have high pandemic potential; consequently, vaccines need to be produced rapidly. MF59® adjuvant reduces the antigen required per dose, allowing for dose sparing and more rapid vaccine availability. Methods Two multicenter, phase II trials were conducted to evaluate the safety and immunogenicity of an MF59-adjuvanted, cell culture–derived, A/H5N1 vaccine (aH5N1c) among 979 adult (18–64 years old) and 1393 elderly (≥65 years old) subjects. Participants were equally randomized to receive 2 full-dose (7.5 μg of hemagglutinin antigen per dose) or 2 half-dose aH5N1c vaccinations 3 weeks apart. Outcomes were based on Center for Biologics Evaluation Research and Review (CBER) and Committee for Medicinal Products for Human Use (CHMP) licensure criteria (titers ≥1:40 and seroconversions on day 43). Solicited reactions and adverse events were assessed ( www.clinicaltrials.gov : NCT01776541 and NCT01766921). Results CBER and CHMP criteria were met by both age groups. CBER criteria for hemagglutination titers were met for the full-dose formulation. Solicited reaction frequencies tended to be higher in the full-dose group and were of mild to moderate intensity. No vaccine-related serious adverse events occurred. Conclusions In adult and elderly participants, the full-dose aH5N1c vaccine formulation was well tolerated and met US and European licensure criteria for pandemic vaccines.

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