A rapid immune response to 2009 influenza A(H1N1) vaccines in adults: a randomized, double-blind, controlled trial.

A double-blind, randomized, controlled trial involving 706 adults was conducted to evaluate the immunogenicity and safety of different dosages of whole-virion or split-virion H1N1 influenza vaccines with or without aluminum adjuvant. A rapid and strong immune response was induced at day 14 after the first injection. The seroprotection rates ranged from 72.7% (95% confidence interval [CI], 62.7%-81.1%) for 5-microg whole-virion aluminum formulation to 97.0% (95% CI, 90.9%-99.7%) for 30-microg split-virion nonaluminum formulation. All formulations were well tolerated. The incidences of mild, moderate, and severe reactions were 71 (10.1%), 15 (2.1%), and 1 (0.1%) of 706 reactions, respectively. The 15-microg split-virion formulation had the best immunogenicity and safety.

Model-based analysis of phosphorus flows in the food chain at county level in China and options for reducing the losses towards green development.

Insight in the phosphorus (P) flows and P balances in the food chain is largely unknown at county scale in China, being the most appropriate spatial unit for nutrient management advice. Here, we examined changes in P flows in the food chain in a typical agricultural county (Quzhou) during 1980-2017, using substance flow analyses. Our results show that external P inputs to the county by feed import and fertilizer were 7 times greater in 2017 than in 1980, resulting in a 7-fold increase in P losses to the environment in the last 3 decades, with the biggest source being animal production. Phosphorus use efficiency decreased from 51% to 30% in crop production (PUEc) and from 32% to 11% in the whole food chain (PUEf), but increased from 4% to 7% in animal production (PUEa). A strong reduction in P inputs and thus increase in PUE can be achieved by balanced P fertilization, which is appropriate for Quzhou considering a current average adequate soil P status. Fertilizer P use can be reduced from 7276 tons yr-1 to 1765 tons yr-1 to equal P removal by crops. This change would increase P use efficiency for crops from 30% to 86% but it has a negligible effect on P losses to landfills and water bodies. Increasing the recycling of manure P from the current 43%-95% would reduce fertilizer P use by 17% and reduce P losses by 47%. A combination of reduced fertilizer P use and increased recycling of manure P would save fertilizer P by 93%, reduce P accumulation by 100% and P loss by 49%. The results indicate that increasing manure-recycling and decreasing fertilizer-application are key to achieving sustainable P use in the food chain, which can be achieved through coupling crop-livestock systems and crop-based nutrient management.

Immunogenicity, safety, and cross-reactivity of an inactivated, adjuvanted, prototype pandemic influenza (H5N1) vaccine: a phase II, double-blind, randomized trial.

BACKGROUND: Avian influenza A virus H5N1 has the potential to cause a pandemic. Adjuvants and whole-virion vaccines are regarded as antigen sparing for pandemic vaccines. METHODS: A double-blind, randomized trial was performed from 28 August to 22 December 2007 in 402 adults; 301 adults were randomly assigned to receive 2 doses of an inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine containing 5, 10, or 15 microg of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 microg of vaccine 14 days apart. The vaccine was manufactured from the recombinant A/Vietman/1194/2004 (NIBRG14) strain. Blood samples were collected for hemagglutination inhibition and microneutralization assays. RESULTS: All formulations were well tolerated, with no serious adverse events. Most local and systemic reactions were mild or moderate. Immune responses were induced after 1 dose in all vaccination groups. The highest immune response was seen after 2 doses of 15 microg of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of > or = 1:40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10- and 15-microg doses met or exceeded European Union licensure criteria. Generally, higher immune responses were elicited in participants vaccinated 28 days apart than those vaccinated 14 days apart. Cross-reaction assays showed that after 2 doses of 10 microg of vaccine, 98% and 87% of participants had a microneutralization titer of > or = 1:40 against heterologous Indonesia and Anhui strains, respectively. CONCLUSIONS: The inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine not only showed good immunogenicity and safety but also elicited significant cross-reactivity against heterologous H5N1 strains in clade 2. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00535665.

Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: a phase I-II randomized trial.

OBJECTIVE: Highly pathogenic avian influenza A virus H5N1 has the potential to cause a pandemic. Many prototype pandemic influenza A (H5N1) vaccines had been developed and well evaluated in adults in recent years. However, data in children are limited. Herein we evaluate the safety and immunogenicity of adjuvanted split-virion and whole-virion H5N1 vaccines in children. METHODS: An open-labelled phase I trial was conducted in children aged 3-11 years to receive aluminum-adjuvated, split-virion H5N1 vaccine (5-30 microg) and in children aged 12-17 years to receive aluminum-adjuvated, whole-virion H5N1 vaccine (5-15 microg). Safety of the two formulations was assessed. Then a randomized phase II trial was conducted, in which 141 children aged 3-11 years received the split-virion vaccine (10 or 15 microg) and 280 children aged 12-17 years received the split-virion vaccine (10-30 microg) or the whole-virion vaccine (5 microg). Serum samples were collected for hemagglutination-inhibition (HI) assays. FINDINGS: 5-15 microg adjuvated split-virion vaccines were well tolerated in children aged 3-11 years and 5-30 microg adjuvated split-virion vaccines and 5 microg adjuvated whole-virion vaccine were well tolerated in children aged 12-17 years. Most local and systemic reactions were mild or moderate. Before vaccination, all participants were immunologically naïve to H5N1 virus. Immune responses were induced after the first dose and significantly boosted after the second dose. In 3-11 years children, the 10 and 15 microg split-virion vaccine induced similar responses with 55% seroconversion and seroprotection (HI titer >or=1:40) rates. In 12-17 years children, the 30 microg split-virion vaccine induced the highest immune response with 71% seroconversion and seroprotection rates. The 5 microg whole-virion vaccine induced higher response than the 10 microg split-virion vaccine did. INTERPRETATION: The aluminum-adjuvanted, split-virion prototype pandemic influenza A (H5N1) vaccine showed good safety and immunogenicity in children and 30 microg dose induced immune response complying with European Union licensure criteria.