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”
The €300m Dutch pension fund for the travel sector has said it was looking for a merger with a larger industry-wide scheme or a switch to defined contribution (DC) arrangements.Reiswerk Pensioenen made clear that continuing independently was not an option because of its funding position and its predominantly young membership. “The long duration as a consequence of our young population requires taking more investment risk,” said Frank Radstake, the scheme’s employer chairman. ”But the financial assessment framework (FTK) doesn’t allow us to do so because of our funding shortfall.”The pension fund was therefore “stuck in the FTK trap.” The small sector scheme has been in trouble since the introduction of a new and lower ultimate forward rate (UFR) in 2015, part of the discount mechanism for liabilities.Despite a defensive investment policy, including a 90% interest hedge, the scheme’s funding level has since plummeted from 125% in 2014 to 99.5%.In its annual report, Reiswerk Pensioenen said it was unable to hedge against the impact of the new UFR, which had caused a steep rise of its long-term liabilities.Radstake said the UFR was expected to drop further and that the current asset mix would not solve the pension fund’s financial problems.He indicated that the scheme’s small size – it has 9,000 active members – was another reason why it wasn’t deemed future-proof.Joining another sector scheme or switching to DC would both give Reiswerk the option to increase the risk profile of its investments.A merger would bring the added benefit of scale, but would also mean an instant rights cut for the scheme’s members.“However, in the long term the results will improve,” said Radstake.Based on its current position, the pension fund was headed for a rights discount in 2021 anyway, he noted.The social partners in the travel industry said they wanted to make a decision about the scheme’s future next summer.
The Wisconsin women’s basketball team used a furious second-half rally to climb back into the game Thursday night, but fell short to South Dakota State 68-65. The first half proved the downfall for the Badgers as they dropped their fourth game in a row.”We just had a horrendous time handling the basketball in the first half,” head coach Lisa Stone said. “I’m disappointed in the first half. We got down and lacked intensity. It was a courageous battle for us to come back, obviously, but it was too little, too late.”South Dakota State had just two field goals in the last 14 minutes of the game, including an eight-minute scoring drought when the Badgers cut it to two. The Badgers trailed by 16 at the half and as many as 21 early in the second half, but went on a 19-0 run that brought the 4,670 in attendance to their feet.The team was sparked by freshman Christine Spencer, who came off the bench to help with defense and even knocked down a 3-pointer for her first points of the year.”I thought we got a nice little lift from Spencer. That’s probably the silver lining of the second half,” Stone said.”When [Christine Spencer] came in, she was determined. Her defense and just our intensity was completely different from the first half,” sophomore forward Danielle Ward said. The teams then traded baskets until the final minute, when Janese Banks, who had a team-high 15 points, hit a runner in the lane to cut it to one with just under a minute to go. On the ensuing defensive possession, Banks took a charge to give the ball back to the Badgers with a chance to take their first lead since early in the first half. Jolene Anderson drove and kicked it to Ashley Josephson, who had a good look, but missed a 3-point attempt. The Badgers fouled, freshman Jennifer Warkenthien missed the first end of a 1-and-1 and the Badgers had a second attempt to take the lead, but Danielle Ward’s jumper rimmed out. This time, Warkenthien dropped both free throws to take a three-point advantage. The comeback attempt came to an end when Banks’ desperation 3 at the buzzer missed everything. Banks earned her first career double-double with 15 points and 12 rebounds, but it wasn’t enough on this day.”[South Dakota State] wasn’t afraid of us at all, and they shouldn’t be,” Stone said. “(Head coach) Aaron (Johnson) does a great job. They are a good team that knows how to win.”Sophomore guard Andrea Verdegan, who finished the game with 19 points, led South Dakota State. The Wisconsin native had hit just three shots from beyond the arc all year, but knocked down five in the game.”I did grow up a Badger fan and it feels nice. This is a big game and I was really excited. We knew that they were going to be really tough, especially on their home court,” Verdegan said.The South Dakota State defense caused the Badgers fits all day as evidenced by the total number of turnovers (26) to field goals made (25) by the Badgers.”We feel like if we just allowed Wisconsin to go through their half-court offense and execute and have to try and stop those guards, it would be really hard to do that,” Johnson said. “Defensively, one of the things we try to do is be really distracting. We’re not always going to be the quickest and most athletic team out there, but we have a style and a system that really requires us to try and disrupt other offenses.”Wisconsin must now search for answers, and it gets no easier as they head to Lawrence, Kan., for a date with the Jayhawks. The University of Kansas is currently undefeated at 6-0 and is outscoring its opponents by 20.8 points per game. Senior Crystal Kemp leads the team in scoring (15.7) and rebounds (6.5). The last meeting between the two was 10 years ago in the NCAA tournament, where Wisconsin upset the Jayhawks in the first round 73-72. “We have to start over now. Our record is now 0-0. A brand new season starts tomorrow and there’s going to be some changes,” Stone said.