Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

IMPORTANCEThere is a need for improved immunogenicity of hepatitis B virus (HBV) vaccines among young adults with risk of infection.OBJECTIVES To demonstrate manufacturing equivalence of a 3-antigen (3A) HBV vaccine, evaluate noninferiority of seroprotection rate (SPR) of 3A-HBV vs single-antigen (1A) HBV after 2 and 3 vaccine doses, and compare safety and reactogenicity between 3A-HBV and 1A-HBV vaccines. DESIGN, SETTING, AND PARTICIPANTSThis phase 3, double-blinded, randomized clinical trial included healthy adults aged 18 to 45 years randomized to 1 of three 3A-HBV groups or 1 control group receiving 1A-HBV. The trial was conducted at 37 community clinics and academic hospitals in Canada, Europe, the United Kingdom, and the United States between December 2017 and October 2019. Participants were followed up for 48 weeks after the first vaccination. INTERVENTIONS Intramuscular administration of 3A-HBV (10 μg) or 1A-HBV (20 μg) on days 0, 28, and 168. MAIN OUTCOMES AND MEASURES Geometric mean concentration (GMC) of serum hepatitis Bsurface antibodies (anti-HBs) and proportion of participants achieving seroprotection. RESULTSOf 2838 participants, 1638 (57.8%) were women, 2595 (91.5%) were White, and 161(5.7%) were Black or African American. A total of 712 participants (25.1%) were randomized to the 1A-HBV group and 2126 (74.9%) to 3A-HBV. The mean (SD) age at informed consent was 33.5 (8.0) years. The study demonstrated 3A-HBV lot-to-lot consistency, as the 2-sided 95% CIs for each pairwise comparison for the anti-HBs GMC ratios were within 0.67 and 1.50 (eg, adjusted GMC ratio,

AS03-adjuvanted H1N1 2009 pandemic influenza vaccine (3.75 µg or 1.9 µg HA), administered as 2 doses, was highly immunogenic, induced long-term immune response to 6 months, with a clinically acceptable safety profile in children aged 6 months to <9 years of age.

Background. Accelerated immunization schedules may help gain early control of influenza pandemics. We investigated different schedules of an AS03A-adjuvanted H5N1 vaccine.Methods. This phase II, open-label, 6-month study randomized participants (aged 18–64 years) to 2 vaccine doses administered 21 (standard schedule), 14, or 7 days apart, or on the same day. Coprimary end points were that the lower limit of the 98.75% confidence interval 14 days after the last dose must be (1) >40% for seroconversion rate (SCR) (Center for Biologics Evaluation and Research [CBER] criterion) and (2) >50% for seroprotection rate (SPR) (attainment rate for reciprocal hemagglutination inhibition titers ≥40, protocol-defined criterion) for the vaccine homologous strain (A/Indonesia/5/2005). European Committee for Human Medicinal Products (CHMP) immunogenicity criteria were also evaluated.Results. Coprimary end points were achieved (lower 98.75% confidence intervals exceeded defined values). Titers were highest with the standard schedule. Nevertheless, CBER SCR, protocol-defined SPR, and CHMP criteria were met with all schedules for the A/Indonesia/5/2005 strain. There were no significant differences between age groups (18–40 vs 41–64 years). Immune response was robust against drift variants A/turkey/Turkey/1/2005 and A/Vietnam/1194/2004.Conclusions. The AS03A-adjuvanted H5N1 vaccine in accelerated schedules offers a robust immune response against vaccine homologous and drift variant strains, allowing consideration of compressed vaccination intervals.Clinical Trials Registration. NCT00695669.

Because human milk is thought to protect infants from shigellosis, we evaluated milk for immunoglobulin A to Shigella virulence determinants. Milk was preincubated to remove antibodies unrelated to each locus of interest, using defined Shigella and E. coli hybrids containing known Shigella genetic segments prior to immunoblotting. The milk could not be shown to contain antibodies to chromosomally encoded virulence loci except for the expected antibodies to the products of the histidine locus. However, all the milk samples contained antibodies to antigens encoded by the large virulence plasmid. The finding of these antibodies suggests a possible mechanism by which human milk might protect infants. * Corresponding author. pared the major antibodies found in these women with those found in a group of women from Houston, Tex.