Baxter says cell-based H5N1 vaccine did well in trial

first_imgJun 12, 2008 (CIDRAP News) – A pharmaceutical company is reporting good results in the first clinical trial of an H5N1 avian influenza vaccine that uses a whole, killed H5N1 virus grown in cell culture—a combination of techniques that entails some risk but may boost immune response and shorten production time.Low doses of the vaccine, made by Baxter Bioscience, generated immune responses against the vaccine strain of H5N1 in most volunteers and also induced responses against two other H5N1 strains in many of them, according to a report published today in the New England Journal of Medicine (NEJM). Formulations without an adjuvant (immune-boosting chemical) yielded the best responses, and the vaccine caused few side effects.Most H5N1 vaccines tested so far have been produced by the conventional method of growing a genetically modified virus in chicken eggs, which takes several months. The Baxter vaccine was grown in Vero cell cultures, a method said to offer increased speed and flexibility.In addition, Baxter took the unusual step of using a whole, “wild-type” (but inactivated) H5N1 virus in the vaccine, instead of a genetically modified, weakened version. Some evidence suggests that whole-virus vaccines against novel flu strains may be more immunogenic than split-virus or subunit vaccines, and producing them takes fewer steps, according to the authors.However, growing large amounts of a wild-type H5N1 virus poses a risk that the virus might somehow escape and trigger devastating outbreaks in poultry. Consequently, Baxter had to build a high-security (biosafety level 3) facility to grow the virus.The vaccine, called Celvapan, is made in a cell-culture system in Bohumil, Czech Republic, Baxter officials said in a Jun 11 news release. “Baxter’s Vero cell manufacturing process is more rapid due to its ability to use a ‘native’ virus that does not need to be modified to allow growth in chicken eggs, therefore accelerating vaccine production,” the company said.The vaccine uses a clade 1 strain of H5N1 virus that was isolated in Vietnam in 2004, known as A/Vietnam/1203/2004.Six formulations testedThe researchers, led by Hartmut J. Ehrlich, MD, and Noel Barrett, both of Baxter, recruited 284 adults (aged 18 to 45) for the double-blind trial, conducted at one site in Austria and two in Singapore. The volunteers were randomly assigned to receive one of six vaccine formulations: 3.75, 7.5, 15, or 30 micrograms (mcg) with an alum adjuvant, or 7.5 or 15 mcg with no adjuvant. Each volunteer received two doses, 21 days apart.The team assessed immune responses primarily by measuring neutralizing antibodies, defining seroconversion as at least a fourfold increase in antibody titer 21 days after the first and second doses. The scientists assessed antibody reactions not only to the vaccine strain, but also to a 2005 clade 2 strain from Indonesia and a 1997 clade 3 strain from Hong Kong.The highest rates of seroconversion were seen in volunteers who received the vaccine without adjuvant: 69.0% with the 7.5-mcg dose and 68.3% with the 15-mcg dose (after two doses). Similarly, those who received nonadjuvanted vaccine had the highest rates of immune response as defined by a virus neutralization titer of 1:20 or more. With the 7.5-mcg dose the rates were 40.5% after one dose and 76.2% after two doses; with the 15-mcg dose the corresponding rates were 39.5% and 70.7%.The formulations without adjuvant also generated high rates of cross-reactivity against the clade 3 virus, as 76.2% of the 7.5-mcg group and 78.0% of the 15-mcg group had a neutralizing antibody titer of 1:20 or more after two doses. Cross-reactivity against the clade 2 strain was lower: 45.2% at 7.5 mcg and 36.6% at 15 mcg. Statistical analysis showed that the no-adjuvant doses induced significantly higher immune responses to both the vaccine strain and the other two strains than the adjuvanted versions did.The vaccine had a safety profile like that of H5N1 subunit vaccines described previously, the authors report. The most common reaction at the injection site was pain (9% to 27% of volunteers, depending on the formulation), and the most common systemic reaction was headache (6% to 31% of vaccinees). Fever occurred in only 2% to 7%.The results, the authors conclude, show “that a broadly reactive immune response to clade 2 and clade 3 of H5N1 virus can be obtained with the use of a low-dose clade 1 vaccine without adjuvant.” Because the 7.5-mcg formulation without adjuvant yielded the best immune response, Baxter has chosen it for further development, they add.Cell culture’s debut hailedIn an accompanying perspective article in NEJM, Peter F. Wright, MD, cites the introduction of a cell-culture–derived flu vaccine as perhaps the most important innovation represented by the Baxter report. Conventional egg-based technology requires decisions in February concerning the next season’s vaccine strains, he notes. But with cell-culture vaccines, “this schedule could be altered to permit incorporation of late-emerging threats.”A graphic accompanying Wright’s commentary indicates that cell-culture technology would permit mass production of a vaccine within 12 weeks from the time a pandemic flu virus is identified, versus 22 weeks for egg-based technology.Wright, a professor of pediatrics at Dartmouth Medical School in Hanover, N.H., also cites the possibility that using whole virus to make the vaccine resulted in higher immunogenicity. This would be consistent with trial results for the swine influenza vaccine created in 1976. But it is not safe to assume that the Baxter vaccine is more immunogenic than the US-licensed H5N1 vaccine—a subvirion vaccine—because different immunogenicity assays were used for the two products, he adds. Further, the whole-virus vaccines in 1976 triggered the strongest side effects in children, so the new vaccine may have a different safety profile in children than in adults.Wright also says the report raises the question whether large-scale production of vaccine from a wild-type H5N1 virus would be safe. The experience in using wild-type poliovirus to make vaccines is reassuring, he writes, adding that the closed systems used to protect vaccines’ sterility “greatly limit the opportunities for spread.”Pros and cons of whole-virus vaccinesJohn Treanor, MD, who conducts viral vaccine research at the University of Rochester in New York, called the Baxter report “intensely interesting” on multiple counts, including the use of a whole, wild-type virus and cell culture production. Treanor is a professor of medicine and of microbiology and immunology.Commenting by e-mail, he said the question of whole-virus versus subunit vaccines has raised an “intriguing discussion.” Some data suggest that whole-virus vaccines yield better immune responses than subunit vaccines do in hosts with no previous exposure to the virus (as in a pandemic), which makes some intuitive sense, he said. However, this advantage doesn’t hold true with seasonal flu viruses, and there is good evidence that whole-virus vaccines cause more side effects in young children.Whole-virus vaccines might be easier to make, because they require fewer steps, Treanor said. “On the other hand, most of the current manufacturers don’t make whole-virion vaccines, so they would have to significantly change their current process to go back to a whole-virion approach,” he added. Given the pros and cons, it’s hard to say which approach is better, he said.”Then the really interesting thing that Baxter has done is to use the wild-type cleavage sequence,” Treanor added. He explained that H5 viruses are highly pathogenic in birds because their hemagglutinin (HA) surface protein can be cleaved easily by proteases founds in all bird tissues, permitting the virus to bind to and enter cells. “Viruses that have a highly cleaveable HA must be handled under high containment because of the risk that the virus might escape and cause outbreaks of lethal influenza in chickens—an agricultural nightmare,” he said.The standard approach is to use reverse genetics to replace the amino acid sequence at the HA cleavage site with a sequence from a less pathogenic H5 virus, Treanor said. He added that he’s not sure why Baxter chose to use the wild-type sequence, but this approach eliminates the need to use reverse genetics, “and since that requires licensing, maybe that is what they’re trying to avoid.”Still a long way to go Another infectious-disease expert, Michael T. Osterholm, PhD, MPH, welcomed the findings but cautioned that the world is still a long way from having the practical capability to quickly make an effective vaccine in large enough quantities to protect most people in the event of a pandemic.”I think it’s an important step forward in that we’re now reporting results from cell culture, but the pandemic clock is ticking, and there remains considerable confusion about what the different serologic results mean in terms of human protection,” said Osterholm, director of the University of Minnesota Center for Infectious Disease Research and Policy, which publishes CIDRAP News.He called Wright’s commentary a thoughtful analysis of the state of flu vaccine research, but said, “His comments . . . fail to take into account the supply and manufacturing facility requirements to make vaccines for the next pandemic. Even if we had a vaccine today that was an ideal candidate for use in the next pandemic, the international capacity to make vaccines, package them, and provide all of the syringes, needles, and other vaccine support materials for a worldwide campaign are extremely limited.”For example, he said it now takes up to 3 years or even longer for the delivery and installation of equipment to bottle and fill vaccinesBaxter’s news release said the European Medicines Agency accepted the company’s vaccine for licensing review earlier this year. The statement also said a federally supported trial of the product is under way in the United States.Ehrlich HJ, Muller M, Oh HML, et al. A clinical trial of a whole-virus H5N1 vaccine derived from cell culture. N Eng J Med 2008 Jun 12;358(24):2573-84 [Full text]See also: Jun 11 Baxter news releaseNovember 2007 CIDRAP News special report: “The pandemic vaccine puzzle, part 6: Looking to novel vaccine technologies”last_img read more

QPR Supporters Club gesture excites Eberechi Eze

first_img The skillful midfielder contributed 13 goals and eight assists in his 45 appearances to help the club retain their championship status for another season. Meanwhile, Eze’s compatriot Osayi-Samuel was not left out of the party as he bagged the Daphne Biggs Supporters’ Young Player of the Year and Kiyan Prince Goal of the Season award. read also:Eberechi Eze reveals desire of playing football at highest level Both players are still eligible to play for Nigeria and they will be in action again West Bromwich Albion at Hawthorne this Wednesday. FacebookTwitterWhatsAppEmail分享 Eberechi Eze is delighted to be named Sportito Queens Park Rangers Supporters’ Player of the Year for the 2019/20 season. The club made the announcement on their official website and the player also won the other two awards to make three in a season. The 21-year-old was also voted Ray Jones Players’ Player of the Year and the Junior Hoops Player of the Year awards for the 2019/20 campaign. Eze was the star of the season for the club who failed to hit the expected height in the Skybet championship this season.Advertisement Promoted ContentWho Is The Most Powerful Woman On Earth?8 Things That Will Happen If An Asteroid Hits EarthTop 10 Female Disney Villains You’ll Definitely Fall In Love WithCouples Who Celebrated Their Union In A Unique, Unforgettable Way10 Asian Actresses Of Irresistible Beauty8 Shows That Overstayed Their Welcome14 Hilarious Comics Made By Women You Need To Follow Right Now7 Of The Wealthiest Universities In The WorldWho Earns More Than Ronaldo?7 Universities In The World With The Highest Market ValueFantastic-Looking (and Probably Delicious) Bread Art6 Best Natural History Museums In The Worldcenter_img Loading… last_img read more

Hammers hit back to beat Baggies

first_img Dawson had become the first Albion player to score in 370 minutes but the Baggies’ dream start turned into a nightmare before the break. They had recalled Chris Baird and Victor Anichebe with Sebastien Pocognoli, sidelined with a dead leg, and Youssouf Mulumbu, dropping to the bench. West Ham were without midfielder Mark Noble, who failed to recover from the calf injury he suffered in their 1-0 win over Newcastle. It meant Nolan returned with Winston Reid and Mauro Zarate. The Baggies needed a quick start after their recent slump and they got it after 10 minutes. Anichebe and Graham Dorrans had already gone close before they grabbed the goal their start merited. The former was fouled on the left and Dawson arrived unmarked to crash in Dorrans’ free-kick from six yards. The Baggies, so passive in losing to Arsenal on Saturday, seemed to have learned their lessons as they took the game to West Ham, only for their momentum to ebb away. They survived a scramble when Ben Foster saved from Nolan’s hooked shot and Cheikhou Kouyate could not force a leveller. Kevin Nolan and James Tomkins cancelled out Craig Dawson’s early opener as the hosts slipped to their fourth straight defeat. The Hammers, though, remain fifth in the Barclays Premier League after another impressive victory. It lifted the Hammers after their slow start and they took control and, a s against Arsenal, Albion wilted and inevitably conceded on 35 minutes. Referee Mike Jones awarded a free kick after Chris Brunt, who was booked, won the ball from Nolan. Downing’s delivery found Tomkins and, when the ball fell to Andy Carroll, his fine acrobatic volley was saved by Foster – only for Nolan to head in from four yards. Worse was to follow, though, in stoppage time as the Hammers deservedly took the lead. Kouyate forced Foster into a smart save but the keeper was beaten from the resulting corner when Tomkins headed in Downing’s cross. It was abject defending from the Baggies and underlined the soft underbelly of the squad which requires improvement next month. That the Baggies lost the influential Brunt to injury just before the goal was a double blow but they should have levelled eight minutes after the break. Mulumbu, on for Brunt, chipped up to Joleon Lescott but Dawson could only volley his knock-down wide from 10-yards. It was a golden chance but one which summed up the hosts’ waning confidence. Adrian got down smartly to save Anichebe’s fierce angled drive with 27 minutes left but the hosts lacked sparkle. Substitute Silvestre Varela tried to add the missing creativity and his cross saw Anichebe head weakly at Adrian. The lack of cutting edge had Albion fans calling for record signing Brown Ideye and he was thrown on as the hosts tried to rescue the game in the final 10 minutes. It lifted the Baggies and Anichebe continued his duel with Adrian when he turned only for the keeper to save his sharp six-yard effort. And with four minutes left Dorrans sent a volley inches wide but with that missed chance went Albion’s hopes of a recovery. West Ham hit back to win 2-1 at West Brom and heap more pressure on Baggies boss Alan Irvine. Press Associationlast_img read more

Charles Oliveira brags about winning future UFC fight with Khabib Nurmagomedov

first_imgAlso Read- UFC: Dana White Confirms Tony Ferguson Vs Khabib NurmagomedovAlso Read- Khabib Nurmagomedov: Fighter’s Salary, Net Worth, Next UFC Opponent Khabib Nurmagomedov, the ‘Dagestani Eagle’ is at the peak of his career and after two back-to-back successful title defences against Conor McGregor and Dustin Poirier at UFC 229 and UFC 242 respectively, the UFC lightweight champion is expected to face Tony Ferguson in his next fight. No wonder Nurmagomedov is one of the best pound-for-pound fighters in the division and he mauls his opponents. However, there is a lightweight contender who claims that he possesses the ability to dethrone Khabib Nurmagomedov from his undefeated MMA record.  The number 15 ranked Charles Oliveira is currently on a six-fight win-streak and he wants to face Nurmagomedov, only to make him feel what defeat tastes like. Also Read- UFC: Khabib Nurmagomedov Considers Mohamed Salah As Perfect Role ModelUFC: Charles Oliveira thinks he can beat Khabib NurmagomedovWell before you rule out the possibility instantly, Charles Oliveira has finished off all of his last six opponents which include two knockouts and four submissions. The Brazilian holds an MMA record of 28 wins and eight losses. Ever since losing to Paul Felder at UFC 218, he went onto achieve a six-fight win-streak against some of the best fighters of the roster including the likes of Jim Miller, Clay Guida and Jared Gordon in his last fight on November 16. The Brazilian has now fixed his eyes on the 155lbs title and he feels that he can take it away from Khabib. 10 months ago UFC: Conor McGregor gets attacked in Khabib Nurmagomedov’s Russia 9 months ago UFC: Khabib Nurmagomedov considers Mohamed Salah as perfect role model WE RECOMMEND LIVE TV 10 months ago UFC: Dana White confirms Tony Ferguson vs Khabib Nurmagomedov Written By SUBSCRIBE TO US In a recent interview, Charles Oliveira said that Khabib Nurmagomedov has been beating everyone at the top but all those victories came up against stand-up guys. Oliveira feels that his superior Jiu-Jitsu skills can impose a threat on Khabib. The Brazilian also said that he is not afraid to take the game on the ground against Khabib, where the lightweight champion is most comfortable since he is Khabib’s anti-game and also claimed that he is better than Khabib Nurmagomedov in stand-up.  “I think if I win two more fights, maybe I can have the opportunity to fight him (Khabib Nurmagomedov)” said the Brazilian martial artist.Also Read- UFC: Khabib Nurmagomedov Says McGregor Needs 10 Wins Before RematchUFC: Whom will Khabib face after Tony Ferguson?After Khabib vs Tony Ferguson takes place, former double champ Conor McGregor expressed his urge to fight the winner but Khabib has ruled out the possibility. According to Khabib, Conor McGregor needs to win 10 fights in a row if he wishes to face him once again in a re-match. The first encounter between them did not go well for the Irishman as Khabib choked him out in round four of the UFC 229 main-event fight. 10 months ago Khabib Nurmagomedov: Fighter’s salary, net worth, next UFC opponent FOLLOW US Last Updated: 18th November, 2019 19:40 IST Charles Oliveira Brags About Winning Future UFC Fight With Khabib Nurmagomedov After his recent victory against Jared Gordon on November 16, Charles Oliviera said that he can dethrone lightweight champion Khabib Nurmagomedov. Know more. COMMENT WATCH US LIVE 9 months ago UFC: Khabib Nurmagomedov says McGregor needs 10 wins before rematch First Published: 18th November, 2019 19:40 IST Raj Sarkar last_img read more