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Abstract: Despite the eradication of smallpox as a naturally occurring disease, concern persists over its potential use as a bioterrorist agent. The development of a new-generation smallpox vaccine represents an important contribution to a cogent biodefense strategy. We conducted a phase 2 randomized, double-blind, controlled trial at four sites in the United States to determine whether a clonal smallpox vaccine manufactured in cell culture, ACAM2000, is equivalent to the standard calf-lymph vaccine, Dryvax®, in terms of cutaneous response rate, antibody responses and safety. Subjects received either Dryvax® or one of four dose levels of ACAM2000 administered percutaneously using a bifurcated needle. All subjects in the highest ACAM2000 dose group and the Dryvax® group experienced a successful vaccination. Dilution doses of ACAM2000 were associated with success rates below the 90% threshold established for efficacy. There were no differences in the proportion of subjects who developed neutralizing antibody: 94% in the highest ACAM2000 dose group (95% CI, 84–99) and 96% in the Dryvax® group (95% CI, 86–100). No significant differences were seen between the effective ACAM2000 and Dryvax® groups regarding the occurrence of adverse events. One subject who received ACAM2000 developed myopericarditis. In healthy, primary vaccines ACAM2000 has a similar vaccination success rate, antibody response, and safety profile to Dryvax. [Copyright &y& Elsevier]

Objective: To determine the relationship between 25-hydroxyvitamin D (25[OH]D) values and subsequent cancer incidence and mortality., Patients and Methods: We identified all adult patients living in Olmsted County, Minnesota, between January 1, 2005, and December 31, 2011, who had at least 1 25(OH)D measurement and no prior diagnosis of cancer. Cancer outcomes were retrieved starting 30 days after 25(OH)D measurement and until patients' final clinical visit as an Olmsted County resident; December 31, 2014; or death. Cox proportional hazards regression was used to analyze data., Results: A total of 8700 individuals had a 25(OH)D measurement and no history of cancer, with a mean ± SD 25(OH)D value of 29.7±12.8 ng/mL (to convert to nmol/L, multiply by 2.496). The mean ± SD age was 51.5±16.4 years, and most were women (78.1%; n=6796) and White (85.7%; n=7460). A total of 761 individuals developed cancer (skin cancer, n=360; nonskin cancer, n=401) during a median follow-up of 4.6 (interquartile range, 3.4-6.1) years. Compared with participants with 25(OH)D values of 20 to 50 ng/mL (reference group), those with 25(OH)D values less than 12 ng/mL had a greater nonskin cancer incidence (hazard ratio [HR], 1.56; 95% CI, 1.03 to 2.36; P=.04) after adjustment. There was no association between 25(OH)D values and total cancer or skin cancer incidence. Compared with individuals from the reference group, 25(OH)D levels less than 12 ng/mL (HR, 2.35; 95% CI, 1.01 to 5.48; P=.047) and 12 to 19 ng/mL (HR, 2.10; 95% CI, 1.05 to 4.22; P=.04) were associated with increased cancer mortality., Conclusion: Low 25(OH)D levels were associated with increased risk for incident nonskin cancer and cancer-related mortality., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: The tocopherol-based oil-in-water emulsion adjuvant system family (AS03) improves antigen sparing with split-virion H5N1 influenza vaccines, representing an important development for pandemic preparedness. In this phase 1/2 randomized, controlled, observer-blinded study in 680 adults, we assessed the immunogenicity and safety of A/Indonesia/5/05 H5N1 (IBCDC-RG2, clade 2.1) prepandemic candidate vaccines produced at 2 separate manufacturing sites., Methods: Two doses, each of which contained 3.75 microg of hemagglutinin antigen, were given 21 days apart either without adjuvant or with an adjuvant system containing 11.86 mg or 5.93 mg of tocopherol (AS03)., Results: The AS03-adjuvanted A/Indonesia/05/2005 (NIBRG-14) vaccines were significantly more immunogenic than nonadjuvanted vaccine in homologous assays. Neutralizing cross-clade immunogenicity against clades 1, 2.2, and 2.3 was demonstrated at day 42 with all vaccines; at 6 months, seroconversion rates were highest for clade 2.2 (60.7%) and for clade 1 (38.3%). Adjuvantation was associated with increased short-term injection-site reactions (pain) in 80% of participants, with such reactions assessed as being of grade 3 severity for 4.0% of doses. No other safety or reactogenicity concerns were identified over 6 months of follow-up., Conclusions: Humoral responses against the adjuvanted 3.75-microg hemagglutinin antigen vaccines from both manufacturing sites fulfilled European and US licensure criteria for immunogenicity for influenza vaccines.