ABSTRACT
BACKGROUND: Almost 700 cases of human infection with avian influenza A/H7N9 have been reported since 2013. Pandemic preparedness strategies include H7N9 vaccine development. METHODS: We evaluated an inactivated H7N9 vaccine in an observer-blind study in healthy adults aged 18-64 years. Participants (420) were randomized to receive 1 of 4 AS03-adjuvanted vaccines (low or medium dose of hemagglutinin with AS03A or AS03B), one nonadjuvanted vaccine, or placebo. The coprimary immunogenicity objective determined whether adjuvanted vaccines elicited an immune response against the vaccine-homologous virus, 21 days after the second vaccine dose per US and European licensure criteria in the per-protocol cohort (n = 389). RESULTS: All adjuvanted vaccines met regulatory acceptance criteria. In groups receiving adjuvanted formulations, seroconversion rates were ≥85.7%, seroprotection rates ≥91.1%, and geometric mean titers ≥92.9% versus 23.2%, 28.6%, and 17.2 for the nonadjuvanted vaccine. The AS03 adjuvant enhanced immune response at antigen-sparing doses. Injection site pain occurred more frequently with adjuvanted vaccines (in ≤98.3% of vaccinees) than with the nonadjuvanted vaccine (40.7%) or placebo (20.0%). None of the 20 serious adverse events reported were related to vaccination. CONCLUSIONS: Two doses of AS03-adjuvanted H7N9 vaccine were well tolerated and induced a robust antibody response at antigen-sparing doses in healthy adults. CLINICAL TRIALS REGISTRATION: NCT01999842.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Influenza A Virus, H7N9 Subtype/immunology , Influenza Vaccines/adverse effects , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Polysorbates/administration & dosage , Squalene/administration & dosage , alpha-Tocopherol/administration & dosage , Adolescent , Adult , Antibodies, Viral/blood , Drug Combinations , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Healthy Volunteers , Humans , Immunization Schedule , Influenza Vaccines/administration & dosage , Male , Middle Aged , Placebos/administration & dosage , Single-Blind Method , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Young AdultABSTRACT
Premenstrual disorders are characterized by a wide variety of affective and somatic symptoms. This diversity of presenting symptoms has led to the use of many different types of treatment approaches, none of which has proven to be successful in all women with these disorders. Non-pharmacologic options include aerobic exercise, dietary changes and supplementation, and cognitive-behavioral therapy. Of the pharmacologic agents used to treat premenstrual symptoms, 3 selective serotonin reuptake inhibitors have received a Food and Drug Administration (FDA) indication for treating premenstrual dysphoric disorder (PMDD). Agents that are often used off label to treat premenstrual symptoms include spironolactone and oral contraceptives (OCs); gonadotropin-releasing hormone (GnRH) agonists and alprazolam are used less frequently in these patients. OCs have historically had little consistent data from controlled clinical trials to support their efficacy until a number of recent studies showed that an OC containing the novel progestin drospirenone is effective in reducing premenstrual symptoms in many women. A new drospirenone-containing OC formulation that is administered for 24 days in a 28-day cycle has been shown to be effective in treating PMDD.