RESUMEN
IMPORTANCE: Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continue to occur. Hemagglutinin H7 administered alone is a poor immunogen necessitating evaluation of adjuvanted H7N9 vaccines. OBJECTIVE: To evaluate the immunogenicity and safety of an inactivated H7N9 vaccine with and without AS03 adjuvant, as well as mixed vaccine schedules that included sequential administration of AS03- and MF59-containing formulations and of adjuvanted and unadjuvanted formulations. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, phase 2 trial at 5 US sites enrolled 980 adults aged 19 through 64 years from September 2013 through November 2013; safety follow-up was completed in January 2015. INTERVENTIONS: The H7N9 vaccine was given on days 0 and 21 at nominal doses of 3.75 µg, 7.5 µg, 15 µg, and 45 µg of hemagglutinin with or without AS03 or MF59 adjuvant mixed on site. MAIN OUTCOMES AND MEASURES: Proportions achieving a hemagglutination inhibition antibody (HIA) titer of 40 or higher at 21 days after the second vaccination; vaccine-related serious adverse events through 12 months after the first vaccination; and solicited signs and symptoms after vaccination through day 7. RESULTS: Two doses of vaccine were required to induce detectable antibody titers in most participants. After 2 doses of an H7N9 formulation containing 15 µg of hemagglutinin given without adjuvant, with AS03 adjuvant, or with MF59 adjuvant, the proportion achieving an HIA titer of 40 or higher was 2% (95% CI, 0%-7%) without adjuvant (n = 94), 84% (95% CI, 76%-91%) with AS03 adjuvant (n = 96), and 57% (95% CI, 47%-68%) with MF59 adjuvant (n = 92) (P < .001 for comparison of the AS03 and MF59 schedules). The 2 schedules alternating AS03-and MF59-adjuvanted formulations led to lower geometric mean titers (GMTs) of (41.5 [95% CI, 31.7-54.4]; n = 92) and (58.6 [95% CI, 44.3-77.6]; n = 96) than the group induced by 2 AS03-adjuvanted formulations (n = 96) (103.4 [95% CI, 78.7-135.9]; P < .001) but higher GMTs than 2 doses of MF59-adjuvanted formulation (n = 94) (29.0 [95% CI, 22.4-37.6]; P < .001). CONCLUSIONS AND RELEVANCE: The AS03 and MF59 adjuvants augmented the immune responses to 2 doses of an inactivated H7N9 influenza vaccine, with AS03-adjuvanted formulations inducing the highest titers. This study of 2 adjuvants used in influenza vaccine formulations with adjuvant mixed on site provides immunogenicity information that may be informative to influenza pandemic preparedness programs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01942265.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Subtipo H7N9 del Virus de la Influenza A , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/inmunología , Adulto , Factores de Edad , Anticuerpos Antivirales/sangre , Método Doble Ciego , Combinación de Medicamentos , Femenino , Pruebas de Inhibición de Hemaglutinación , Hemaglutinación por Virus/inmunología , Humanos , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Polisorbatos/administración & dosificación , Escualeno/administración & dosificación , alfa-Tocoferol/administración & dosificaciónRESUMEN
Leaf scald, caused by Xanthomonas albilineans, is a major sugarcane disease worldwide. The disease is managed primarily with resistant cultivars obtained through classical breeding. However, erratic symptom expression hinders the reliability and reproducibility of selection for resistance. The development and use of molecular markers associated with incompatible/compatible reactions could overcome this limitation. The aim of the present work was to find leaf scald resistance-associated molecular markers in sugarcane to facilitate marker-assisted breeding. A genetic linkage map was constructed by selective genotyping of 89 pseudo F2 progenies of a cross between LCP 85-384 (resistant) and L 99-226 (susceptible) using 1,948 single dose (SD) markers generated from SSR, eSSR, and SNPs. Of these, 1,437 SD markers were mapped onto 294 linkage groups, which covered 19,464 cM with 120 and 138 LGs assigned to the resistant and susceptible parent, respectively. Composite interval mapping identified 8 QTLs associated with the disease response with LOD scores ranging from 3.0 to 7.6 and explained 5.23 to 16.93% of the phenotypic variance. Comparative genomics analysis with Sorghum bicolor allowed us to pinpoint three SNP markers that explained 16% phenotypic variance. In addition, representative stress-responsive genes close to the major effect QTLs showed upregulation in their expression in response to the bacterial infection in leaf/meristem tissue.
RESUMEN
The aim of this study was to evaluate the release of pro- and anti-inflammatory as well as anabolic mediators stimulated by a leukocyte-reduced platelet-rich gel supernatant (Lr-PRGS) and a leukocyte-reduced plasma supernatant (Lr-PL) at two concentrations (25 and 50%) on normal equine suspensory ligament explants (SLEs) and tendon explants (TEs). SLEs and TEs from six horses were independently incubated for 48 h with Lr-PRGS and Lr-PL at concentrations of 25 and 50%, respectively. Samples were collected from the incubated tissues at 1 h and 48 h, which were employed for ELISA determination of interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), IL-4, IL-1 receptor antagonist (IL-1ra), platelet-derived growth factor isoform BB (PDGF-BB), transforming growth factor beta-1 (TGF-ß1, and hyaluronic acid (HA). Overall, 50% Lr-PRGS induced significantly less IL-1ß release than the other hemoderivatives in both tissues. At 48 h, both Lr-PRGS and 25% Lr-PL induced significantly higher TNF-α concentrations in SLEs when compared to TEs, whereas both Lr-PRGS concentrations induced significantly higher IL-4 concentrations in SLEs in comparison to TEs. IL-1ra release was not different between tissues. However, this cytokine was significantly higher in tissue explants cultured with both Lr-PRGS concentrations. HA concentration was lower in tissue explants cultured with all hemoderivatives at two concentrations when compared to the control group. The positive effects observed for ligaments and tendons treated with Lr-PRGS may be mediated by the inhibition of IL-1ß release of and increased release of IL-4 and IL-1ra. Furthermore, PDGF-BB could be a polypeptide responsible for mediating the release of anti-inflammatory cytokines in SLEs and TEs incubated with Lr-PRGS.