Sept 7, 2006 (CIDRAP News) – In a human trial in China, a whole-virus H5N1 avian influenza vaccine generated an immune response with a relatively low dose of antigen, suggesting that it could be used to immunize more people than may be possible with some other vaccines under development.The study, published online today in The Lancet, showed an adequate immune response in 78% of volunteers after two 10-microgram (mcg) doses of the vaccine plus an aluminum hydroxide (alum) adjuvant. That exceeds the European Union’s requirement of an acceptable response (a hemagglutinin-inhibition titer of 40 or more) in 70% of volunteers.The vaccine is made by Sinovac Biotech in Beijing, China, from an inactivated strain of H5N1 known as Vietnam/1194/2004. The report says that Sinovac was involved in designing and monitoring the study but played no role in collecting the data or writing the report.The randomized, placebo-controlled, double-blind study involved 120 adults (aged 18 to 60). They were divided into five groups of 24, with each group receiving either a placebo or 1.25, 2.5, 5, or 10 mcg of the vaccine.Each volunteer received the vaccine on the first day of the study and 28 days later. Serum samples were assessed for evidence of an immune response on days 0, 14, 28, 42, and 56.An antibody response was seen after the first injection at all dose levels. The highest response (78% seropositivity) was seen in the 10-mcg group after two doses.The investigators reported that all four doses were well tolerated, even though whole-virion vaccines are generally thought to cause more reactions than split-virion vaccines. No serious reactions were reported, and most local and systemic reactions were mild and brief. Three people dropped out of the study, and one person was excluded from the final analysis.The authors concluded that the dose required to reach an acceptable immune response was much lower than for vaccines reported in previous studies. Two reports published earlier this year described trials of a split-virus H5N1 vaccine developed by Sanofi Pasteur. The reports said two 90-mcg doses of nonadjuvanted vaccine or two 30-mcg doses of adjuvanted vaccine were required to produce the desired immune response.(In July, GlaxoSmithKline reported a good immune response in 80% of volunteers who received a dose of only 3.8 mcg of the company’s adjuvanted H5N1 vaccine. However, a full report of those findings has not yet been published.)”The manufacturing capacity for an H5N1 vaccine would increase if a whole-virion vaccine is used, because 20% to 30% of vaccine antigen is expected to be lost during the disruption process in the preparation of split-virion vaccines, according to our experience with seasonal influenza vaccine,” the Chinese researchers write.In an accompanying commentary, Iain Stephenson, MD, of the Infectious Diseases Unit at Leicester Royal Infirmary in Leicester, England, writes that the findings point up of “a potential dose-sparing approach that could be crucial for a global supply of pandemic vaccine.”He says that trial results for split-virion H5N1 vaccines have been disappointing, because within current manufacturing constraints, the two such vaccines under development would yield only enough to vaccinate 75 million to 225 million people.Though whole-virion vaccines generally produce a better immune response than split or subunit vaccines, development of whole-virion H5N1 vaccines has been delayed, Stephenson writes. He says it is difficult for manufacturers that produce split seasonal vaccines to switch production approaches and processing methods.Stephenson cautions that whole-virion vaccines have been associated with febrile reactions in children and emphasizes that careful investigation is needed before such vaccines can be widely used.It remains to be seen whether whole-virion vaccines can induce the broad cross-reactive response that would be needed to treat a variety of H5N1 viruses, Stephenson writes.Lin J, Zhang J, Dong X, et al. Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase 1 randomised controlled trial. Lancet 2006 (early online publication, Sep 7) [Abstract (registration required)]Stephenson I. H5N1 vaccines: how prepared are we for a pandemic? (Commentary). Lancet 2006 (early online publication, Sep 7)See also:May 12 CIDRAP News story “Sanofi reports results for H5N1 vaccine with adjuvant”Jul 26 CIDRAP News story “Glaxo says its H5N1 vaccine works at low dose”
Tottenham face an arduous task to keep their Champions League hopes alive after defeat at home by the highly impressive RB Leipzig in the first leg of their last-16 tie.Spurs, now stripped of long-term injury victim Son Heung-min with a broken arm as well as Harry Kane, were beaten more convincingly than the scoreline suggests as the side lying second in the Bundesliga demonstrated their growing stature.And it was only a masterclass from goalkeeper Hugo Lloris that gives Spurs hope for the second leg in Germany, keeping Leipzig at bay with a string of outstanding saves before he was beaten by Timo Werner’s 58th-minute penalty.Lloris turned Angelino’s shot on to the post and saved from Werner inside the first minute, later denying the striker once more from point-blank range.He was powerless to stop Werner’s drilled spot-kick after Ben Davies fouled Konrad Laimer but kept Spurs in it with a crucial block from Patrik Schick.Spurs finally forged chances of their own after the break, with Leipzig keeper Peter Gulacsi turning Giovani Lo Celso’s free-kick on to the post and Lucas Moura heading over from close range – but it is advantage to Julian Nagelsmann’s team.Spurs suffer from lack of threatThe big question for Spurs and manager Jose Mourinho was how they would lay a glove on RB Leipzig after the blow of losing Son to a broken arm exacerbated the long-term absence of main marksman Kane.And so it proved as, despite a much-improved second half, they could not apply consistent pressure to Leipzig, who will go into the second leg as firm favourites to reach the quarter-finals.Spurs should not be written off after the heroics of last season but without Kane and Son it would be an outstanding feat if they were to overturn this deficit.Mourinho at least had shining lights in goalkeeper Lloris and midfield man Lo Celso, the France keeper preventing Leipzig from reducing the second leg to little more than a formality.It was an ominous sign that he was in frantic action inside the first minute and he can take credit for Leipzig not being out of sight already.Lo Celso, meanwhile, showed his growing maturity as he drove Spurs forward, almost equalising with a fine 25-yard free-kick that was turned on to the post by the stretching Gulacsi.It was, however, a night of frustration for Spurs – summed up by the sight of a stony-faced Dele Alli hurling a water bottle and a boot in the dugout after he was substituted.Spurs must call on the Champions League spirit of last season to turn this last-16 tie around. Source: BBC
Sophomore guard Zachary Winston of Albion College in Michigan — the brother of Michigan State All-American Cassius Winston — was struck by a train and killed on Saturday night.The Detroit Free Press reported that an Amtrak passenger train with 65 passengers aboard struck a pedestrian running on the tracks through Albion at 8:41 p.m. An Amtrak spokesperson told the Free Press the family of the victim had been notified. Police said ge purposefully stepped in front of the train, per the Free Press. Albion president Dr. Mauri Ditzler acknowledged the loss of Zachary Winston, although chose not to identify him so soon after the accident. Along with a promise to offer grief counseling to the college community and more details later Sunday, he issued a statement.“Last night, our family lost a student. And as families do in difficult times, we must come together to mourn and to embrace one another,” he said. “We have been in close contact with the student’s family and are doing everything we can to support them.“In accordance with the family’s wishes, we are not sharing a name or details at this time. Please keep the family close in your heart.” Zachary Winston, 19, was a product of Detroit Jesuit High (Detroit). He played 15 minutes off the bench and scored three points in Albion‘s season-opening loss to Mount Union on Friday.His brother, Cassius, is a senior for the top-ranked Spartans, a member of the 2019 Sporting News All-America team and the 2019 Big Ten Conference Player of the Year. He led Michigan State to the Final Four last April, its eighth appearance under coach Tom Izzo.MSU is scheduled to play Sunday night against Binghamton in East Lansing.