Jul 30, 2007 (CIDRAP News) – Acambis, a British biotechnology company, recently announced the launch of a phase 1 clinical trial of an influenza vaccine designed to provide a stable shield against seasonal and pandemic flu strains and eliminate the need to overhaul the flu vaccine each year.Known as ACAM-FLU-A, the vaccine is designed to target all influenza A virus strains, Acambis said in a Jul 17 press release. If successful, the product will mark a major step toward a universal flu vaccine—one that would protect against all strains of both influenza A and B. The majority of laboratory-confirmed flu cases each year in the United States are type A.The randomized, double-blind, placebo-controlled, multicenter trial will be conducted in the United States. Investigators will assess the vaccine’s safety, tolerability, and ability to generate an immune response in up to 80 healthy volunteers between ages 18 and 40, the company said.The trial will also assess the effectiveness of two adjuvants (immune-boosting chemicals): aluminum hydroxide, widely used in licensed vaccines, and QS-21 Stimulon, an investigational adjuvant licensed from Antigenics, Inc., according to Acambis.Michael Watson, Acambis’ executive vice-president for research and development, said in the press release that an effective universal vaccine will not require reengineering each time the virus mutates. Such a vaccine could be manufactured continuously, and people could be immunized any time of year.”It could be stockpiled in advance of a pandemic or potentially used routinely to ensure population protection against future pandemics,” Watson said, adding that Acambis hopes to see results of the study by the end of the year.Frequent minor changes in flu viruses involve two surface proteins, hemagglutinin and neuraminidase, represented by the H and N in virus names, such as H3N2. The two proteins allow flu viruses to enter host cells and then exit them after replicating. Because the H and N components are highly mutable, vaccine makers must adjust the flu shot components every year to match circulating strains.However, Acambis’s vaccine involves a more stable viral protein called M2, the ion channel protein. The company said the key component in its flu vaccine is M2e, the extracellular domain of M2, which is specific to influenza A. The hope is that M2e will produce an immune response against all influenza A stains, according to Acambis.ACAM-FLU-A is a recombinant vaccine that uses a hepatitis B virus core protein to deliver M2e, the company said.Acambis also said it is searching for a similarly conserved region on influenza B virus strains so that it can offer a vaccine that protects against all human seasonal flu strains.Universal influenza vaccines are under investigation by several other groups, including the Wistar Institute in Philadelphia and Dynavax Technologies in the San Francisco area, among others.Walter Gerhard, professor of immunology at the Wistar Institute, and colleagues wrote in an April 2006 Emerging Infectious Diseases (EID) article that the hope is that universal vaccines can replace current vaccines. But they wrote that even if universal vaccines only reduce, without preventing, clinical disease, they will still be an important adjunct to conventional vaccines, particularly for high-risk groups.Gerhard and colleagues wrote that, in the face of a major new flu variant, maternal antibodies generated by universal vaccines could give newborns some protection. Also, in elderly people a universal vaccine could induce memory B cells, which tend to be maintained into old age and can be recalled by booster vaccination, to generate protective antibodies. The article said the effectiveness of current vaccines depends heavily on “naïve” B cells, which frequently decrease as people age.”When all factors are taken into account, protection against influenza virus infection likely can be improved by a universal vaccine,” the authors wrote.See also:Aug 25, 2005, CIDRAP News story “Acambis hopes to build a flu vaccine that lasts”Apr 2006 EID article on prospects for a universal influenza vaccine
“I’ve seen slides all year long,” Mattingly said. “I’ve seen a number of them look just like. You’re trying to break up two. I think as you’re going full speed, you’re trying to break up two. I don’t think you’re — again, I saw the slide. He hit the ground first. Yeah, I’ve seen people say it’s late. You could say it was late, but to me it was legal.”Torre was the Dodgers’ manager from 2008-10, when Mattingly was the club’s hitting coach, and the Mets’ manager from 1977-81.The Dodgers said in a statement that they “stand behind Chase Utley and his decision to appeal the suspension issued (Sunday) by MLB.”Chris Guccione, the second base umpire in Game 2 Sunday, did not rule Utley out for interference. In fact, after the Dodgers challenged Guccione’s “out” call, Utley was allowed to stay on second base — despite never making contact with the bag – because Tejada’s foot was off the bag when he received the throw from Daniel Murphy and Utley left the field thinking he was out.Torre defended Guccione’s judgment after the game, but reversed course in his statement Sunday.“The determination of whether a baserunner has intentionally interfered with a player attempting to turn a double play is left to the judgment of the umpire on the field, and that judgment call is not subject to review,” Torre said. “I should add that determining where to draw the line between an illegal slide and a legitimate hard play is an extremely difficult call for our umpires.“However, after thoroughly reviewing the play from all conceivable angles, I have concluded that Mr. Utley’s action warrants discipline,” Torre continued. “While I sincerely believe that Mr. Utley had no intention of injuring Ruben Tejada, and was attempting to help his club in a critical situation, I believe his slide was in violation of official baseball rule 5.09(a)(13), which is designed to protect fielders from precisely this type of rolling block that occurs away from the base.”Torre said that the league will experiment with a rule requiring runners to slide into second base during the upcoming Arizona Fall League season.That’s of little consolation to the Mets, who are now without their starting shortstop for the remainder of the postseason. Wilmer Flores will replace Tejada in the starting lineup. Triple-A infielder Matt Reynolds is expected to be officially added to the Mets’ playoff roster today.“I said entering this series defense is going to be important, very important,” Collins said Saturday. “So we thought (Tejada) would be the guy. Now we’re going to have to ask Wilmer to step up. Relax, play with a little relaxation that I don’t think there is any pressure on him. Just play the game the way he knows how. And I think he will.”Before the suspension was announced Sunday, Collins reiterated that he believed Utley’s slide was late.“Where he hit Ruben on the field, certainly was something that needs to be addressed,” Collins said. “A two-game suspension for a legal baseball play is outrageous and completely unacceptable,” Wolfe said in his statement. “Chase did what all players are taught to do in this situation — break up the double play. We routinely see plays at second base similar to this one that have not resulted in suspensions. Chase feels terrible about Ruben Tejada’s injury and everyone who knows him knows that he would never intentionally hurt anybody.”Utley expressed regret over the injury Saturday night in postgame interviews and apologized to Tejada via a text message to Mets third baseman David Wright, according to one report.MLB’s Chief Baseball Officer, Joe Torre, ruled that Utley’s slide violated rule 5.09(a)(13). This rule declares a batter – in this case, Howie Kendrick – is out when “a preceding runner shall, in the umpire’s judgment, intentionally interfere with a fielder who is attempting to catch a thrown ball or to throw a ball in an attempt to complete any play.”Baseball’s rulebook goes on to state that “the objective of this rule is to penalize the offensive team for deliberate, unwarranted, unsportsmanlike action by the runner in leaving the baseline for the obvious purpose of crashing the pivot man on a double play, rather than trying to reach the base. Obviously this is an umpire’s judgment play.”Dodgers manager Don Mattingly told reporters Sunday that he believed Utley’s slide was legal. Newsroom GuidelinesNews TipsContact UsReport an Error Major League Baseball suspended Dodgers infielder Chase Utley two games Sunday for his slide that injured Mets shortstop Ruben Tejada in the seventh inning of Game 2 of the National League Division Series. Utley’s agent, Joel Wolfe, said in a statement that Utley will appeal the suspension.The series resumes Monday, with Game 3 scheduled for 5:37 p.m. Pacific Time at Citi Field. Utley is allowed to play until the appeal process is complete. If he loses the appeal, the Dodgers’ roster would be reduced to 24 players. Given the timing and importance of the suspension, the process could be expedited prior to Game 3.Tejada suffered a fractured right fibula on the play.