Jun 27, 2005 (CIDRAP News) – You’ve got to gather a lot of eggs to supply the world with influenza vaccine, but that might change before long.As governments and scientists wrestle with how best to protect people from the annual onslaught of typical flu and the unpredictable attack of pandemic flu, they’re seeking alternatives to egg-based vaccines.A production method common to other vaccines, cell culture, is increasingly gaining currency. Cell-culture technology involves growing key vaccine components in human, monkey, canine, insect, or other cells in enclosed vats.The process has been used for vaccines such as polio, hepatitis A, chickenpox, and shingles, said Robin Robinson, PhD, senior project officer for the Office of Public Health Emergency Preparedness in the US Department of Health and Human Services (HHS).Growing flu vaccines in cell cultures would mark a huge departure from the traditional method.The decades-old production method used today involves growing vaccines in fertilized chicken eggs. It depends on the availability of hundreds of millions of eggs and requires adapting the virus strain to grow in eggs. The production process takes at least 6 months, according to the National Institute of Allergy and Infectious Diseases. And in the event of an emergency, there is no way to quickly scale up the supply, since eggs must be ordered in advance.With cell-culture methods, the virus does not need to be adapted for growth in eggs, and in an emergency, manufacturers could boost production without waiting for chickens to lay enough eggs. Although estimates vary as to how much time would be saved with cell-culture production, experts familiar with both methods say it could shorten the process by at least a month.Besides being faster, production of cell-culture vaccines is considered safer and cleaner than egg-based systems because it uses a closed system of bioreactors.An improving climateDespite the disadvantages of egg-based vaccines, however, there has been little pressure to pursue cell culture. The functional egg-based infrastructure, the relatively low profits for flu vaccines, and the challenges of adapting the flu virus for cell culture production have slowed research and development, authorities say.Egg-based vaccines “have always been a very cheap product, and there was never a real incentive in the industry to change that process,” explained Manon Cox, DrS, MBA, chief operating officer of Protein Sciences Corp. in Meriden, Conn., in a recent interview. Protein Sciences is developing a cell-culture flu vaccine using caterpillar cells.The climate for cell-culture flu vaccines is improving because of shortages in the US vaccine supply and the growing fear that the next pandemic could be brewing right now in Southeast Asia.While some companies have been researching cell-culture techniques for years, others now have incentives to join the push. The United States has worked in the last year and a half to encourage a number of contracts to “secure, expand, and diversify the influenza vaccine supply in the United States” for both seasonal and pandemic flu, Robinson said.HHS in April awarded vaccine maker Sanofi Pasteur a $97 million, 5-year contract to develop cell-culture technology. The contract is for developing the technology and design for a facility to manufacture at least 300 million doses of vaccine for use in a pandemic.HHS has already issued another request for proposals to boost flu vaccine research and development, Robinson said. The contracts call for producing a pandemic flu–like vaccine that must go through phase 1 and 2 clinical trials “so they have a candidate that will be both safe and immunogenic,” he said.Bruce Gellin, director of the National Vaccine Program at HHS, explained why it’s important to end the era of the egg in testimony before a congressional subcommittee on Apr 12:”Using a cell culture approach to producing influenza vaccine offers a number of benefits. Vaccine manufacturers can bypass the step needed to adapt the virus strains to grow in eggs. In addition, cell culture–based influenza vaccines will help meet surge capacity needs in the event of a pandemic or shortage. US licensure and manufacture of influenza vaccines produced in cell culture will also provide security against risks associated with egg-based production, such as the potential for egg supplies to be contaminated by various poultry-based diseases.”Cell-based techniques would allow manufacturers to double or triple vaccine production, from, say, 10 million doses a week to perhaps 20 million or 30 million, Robinson said.In addition, safety could be greatly improved with cell-culture vaccines, he noted. Egg-based vaccine production involves open systems, whereas cell-culture production involves a bioreactor, which is a closed system. Cell-culture technology far safer from contamination by pathogens, which would be of crucial importance in the event of a pandemic, he said.Caterpillar cells as vaccine factoriesSanofi Pasteur is but one of several companies working to develop cell-culture flu vaccine, according to a list Robinson compiled. They include Solvay Pharmaceuticals of the Netherlands, Baxter in Austria, Chiron in Germany, GlaxoSmithKline in Belgium, ID Biomedical of Canada, and Medimmune in the United States. None of the vaccines is on the market yet.”Today everybody is trying to do this,” said Cox, of Protein Sciences.Protein Sciences is betting on the baculovirus system for its cell culture flu vaccine. The baculovirus has a reputation in nature for easily infecting insect cells, Cox said.Protein Sciences’ process starts with recombinant hemagglutinin (rHA), she said. Hemagglutinin (H) and neuraminidase (N) are the surface proteins of the flu virus. H helps the virus bind to and enter host cells, and N enables new copies of the virus to leave a cell so they can infect others.The rHA is essentially zipped up like DNA, creating a more stable, less shift-prone blueprint, Cox said. The rHA is inserted into a baculovirus, and the baculovirus is added to caterpillar cells.”The rest happens on its own,” Cox said. “There’s an infection, the baculovirus infects the insect cells, and it sets about producing the product of interest [baculovirus copies containing rHA]. The insect cell is a little factory, which is now starting to produce whatever that baculovirus wants it to produce.””Vaccine manufacturers have recognized that this baculovirus system is an enormously powerful system to make vaccines against viral or parasitic diseases,” she said. “We need to convince venture capitalists and other partners that this is indeed the product to go for,” she added. It will probably be 3 years before the company seeks FDA approval.The company’s efforts may have taken a stride forward with the announcement in mid-June of preliminary results from its initial field efficacy study of the FluBlOk vaccine, made through the process described above.The study included 460 healthy people aged 18 to 49 at three US sites, according to a news release from the company. Subjects were injected with one of two different formulations of FluBlOk, with the same amount of H3 antigen but two different amounts of H1 and influenza B antigens, or with a placebo. The 135-microgram dose was 100% efficacious in preventing culture-positive influenza compared with the placebo, the company said. In addition, the vaccine groups had a 50% lower rate of flu-like illness than the placebo group.The trial showed safety and induced strong antibody responses against influenza in all vaccinated subjects, the company said, adding that final assessments are still under way.Seeking licensing in the Netherlands, USThe Dutch company Solvay Pharmaceuticals has been working on a cell-culture flu vaccine since the early 1990s, according to Bram Palache, MSC, PhD, biochemist and global medical affairs director for influenza vaccines.Solvay’s vaccine is made in canine cells, a line that has been approved for use in the Netherlands, although it wasn’t approved when Solvay selected it, Palache said. The company is in the process of validating its factory, and hopes to make clinical lots there this year. From there it’s a relatively short step to final licensure of the flu vaccine for use in the Netherlands, he added.Solvay is seeking US Food and Drug Administration approval of the flu vaccine and the cell line used to produce it, Palache said. He was not ready to speculate on how long it might be before the vaccine would be available in the US.The importance of alternatives to eggs for vaccine production came home to Solvay in 2003, when the company lost chickens during an outbreak of H7N7 avian flu in the Netherlands. The company had to scramble to get approval to bring in eggs from disease-free areas so it could produce flu vaccine on time.”We had a real-life situation where the vulnerability of eggs for the production of influenza vaccines was really making the difference between having vaccine and having no vaccine,” Palache said. “There’s nothing wrong with egg production per se. But once the cell-culture vaccine is implemented . . . more companies will come in, using that technology. Ultimately it will replace the current production technology.”Cell culture just part of US strategyRobinson cautioned that in the flu vaccine arena, there are more pressing short-term goals than developing cell-culture technology. “We approach it in two phases. One is preparedness to hopefully have stockpiles of a virus that is as close as we think it can be to the [potential pandemic] threat. And then to have the manufacturers ready to go with virus seed strain. And then to have the capacity.”The short-term US goals are aimed at improving the current flu vaccine production processes to improve yield and making the available vaccine supplies stretch further, he said. The goals include developing adjuvants to boost immune response and finding alternative methods for injecting the vaccine.Robinson said he wants the nation to have the surge capacity to produce at least 20 million doses of monovalent vaccine per week by 2009.Ultimately, what the United States would need for a pandemic flu strain is 600 million doses of vaccine—two doses for every American. Compare that with the numbers for the 2004-05 flu season: Authorities hoped to have 100 million doses available, but obtained only 61 million. The leap from the unmet goal of 100 million doses to 600 million is so daunting that even experts such as Robinson break down the numbers.”That’s why we like to talk about it in terms of weeks,” he said.And while cell-culture technology may improve flu vaccine production capacity, it is not a panacea for the challenge of a flu pandemic. A vaccine cannot be specifically tailored to a pandemic virus until the virus emerges, so even with cell-culture technology, an optimal vaccine would not be available for the first several months of a pandemic.Moreover, only nine countries have the capacity to produce flu vaccine on a commercial scale. The advent of cell-culture technology does not automatically solve the problem that current global annual production capacity is fewer than 1 billion doses of flu vaccine in a world of more than 6 billion people—or the challenge of actually administering vaccine to billions of people in a pandemic situation. And even if the United States could eventually secure enough doses for its own population, the nation would not be immune to the global economic disruption that a pandemic would cause.Aside from pandemic-related concerns, Palache said that switching production methods won’t address a key problem with flu vaccine: demand.”[Neither] Solvay nor any other company will produce three times as much vaccine just because they can do it if by the end of the day it isn’t sold. Flu vaccines can’t be put on the shelf for the next year,” he said. “Whether they’re eggs or cells, demand drives supply.”See also: Transcript of Bruce Gellin’s testimonyhttp://www.hhs.gov/asl/testify/t050412.html
Image courtesy of GAILState-run gas company GAIL India has reportedly offered a couple of liquefied natural gas cargoes loading from Dominion’s Cove Point facility in Maryland. Citing industry sources, Reuters reports the two cargoes are to be loaded in August and November and will be sold on a free-on-board (FOB) basis.The $4 billion Cove Point facility, with a nameplate capacity of 5.25 mtpa, began producing LNG in March last year with the facility shipping its first commercial cargo the following month.GAIL has booked a total of 5.8 million tons of U.S. LNG per year on long term deals with Cheniere and Dominion from their respective Sabine Pass and Cove Point natural gas liquefaction and export projects.However, due to the price-sensitive India’s market, the company has been forced to seek swap deals.In addition, GAIL is looking to purchase a liquefied natural gas cargo for delivery to the Dahej LNG terminal in late December on a delivered-ex-ship (DES) basis.The tender for this swap deal is closing on July 3. LNG World News Staff
The Teranga Lions of Senegal has booked its place at the 2018 World Cup to be staged in Russia after its long years of absence since 2002. Senegal, under their manager, Aliou Cisse has found a new lease of life. On the African stage, their best performance ever was a runners-up finish during the 2002 AFCON where they lost to Cameroon. Senegal were also very impressive during the qualifying rounds for the World Cup as they won five and drew one of the six games played. They came out unscathed in a group which featured AFCON 2013 finalists, Burkina Faso as well as Cape Verde Islands and South Africa. A flashpoint of Senegal’s qualification was the game against South Africa where due to manipulation by Ghanaian referee Joseph Lamptey, the game in which Senegal lost by 2-1 under bizarre circumstances was replayed. Senegal went on to win the replay. Joseph Lamptey was subsequently given a lifetime ban. COACH AND PLAYING STYLE Coached by former captain Aliou Cisse, Senegal has been taken out of the dark shackles of football to become a very fearsome physical and attacking side. Aliou Cisse has gathered years of experience as a footballer as he played for Losc Lille, PSG, Sedan, Montpellier, Birmingham City, Portsmouth and Nimes and further captained the Teranga Lions during their maiden world cup appearance in 2002. He has galvanized his men into delivering some wonderful football. The Senegalese are a very physical team with incredible endurance and they play to their strengths. A fluid 4-3-3 formation ensures that they utilize the pace and trickery of Mane upfront while a midfield trio of Gueye, N’diaye and Kouyate ensures that they outrun opposing midfielders. With Kalidou Koulibaly controlling the defence, Aliou Cisse has got a fantastically balanced side who will definitely look to cause major upsets in the tournament. FORM Heading into the world cup, Senegal is ranked 27th in the latest FIFA rankings. Senegal played out a frustrating 1 all draw game with Uzbekistan. Senegal failed to utilize most of the chances they created during the game. They were shockingly wasteful. In their next friendly game against Bosnia, both teams failed to hit the back of the net and hence settled for a goalless draw. Senegal also drew 0-0 with Luxembourg raising genuine concern about their potency in front of goal. In their last friendly game, Senegal took the lead but slumped to a 2-1 defeat to Croatia. Senegal has been unimpressive in their displays during the friendlies so far but these games are not indicative of one’s true strength as a team. THE BIG ONE Aliou Cisse, the fiercely intelligent and cultured dreadlocked individual has not minced words about his expectations as a local coach. He is one who intends to change the status quo. He said “This is a great generation. What we are changing is the mindset. It is not just about playing a pass or some technical skill. It is about raising the whole level of African football. That’s our objective. HISTORY IN THE WORLD CUP The Teranga Lions roared very loudly during their maiden appearance at the world cup. They stunned the footballing world when they defied all odds to defeat the then defending champions France in their opening world cup game by a solitary goal to nil. A 1-1 draw with Denmark preceded an exciting 3-3 draw with Uruguay. With 5 points, Senegal booked their place in the round of 16 where they came from a goal down to defeat Sweden by 2 goals to 1. That sealed their progress to the quarter-finals where they were eliminated Turkey in extra time via the golden goal rule. KEY PLAYERS The Senegalese on everyone’s lips heading into this world cup season is none other than Sadio Mane. Mane is blessed with incredible acceleration and an ability to dribble pass his opponents. There are also the likes of Napoli’s stalwart ball playing defender, Kalidou Koulibaly as well as Monaco’s Diao Keita Balde. OPPONENTS AND PREDICTIONS Senegal will begin their quest for world cup glory on the 19th of June when they take on Poland. Poland striker Robert Lewandowski is definitely the player the Senegalese has to watch out for as he has a big influence Poland’s playing style. We expect Koulibaly to neutralize the threat of Koulibaly. Senegal’s front three will also have to go through a rock in Poland’s defence. Kamil Gilik, dubbed by the French media as “the rock” has built a reputation for himself as a rugged defender with an ability of scoring incredible goals. Grzegorz Krychowiak is also one to look out for in the Poland setup. He expertly closes down space in front of the defence and breaks up opposition attacks with ease. Though a move to French money bags PSG backfired, Krychowiak still offers a lot to this Poland side. Senegal can find solace in the fact that after Nawalka switched to a three-man defence from the back 4, Poland has not really been impressive. Poland’s over-reliance on Lewandowski will also cost them as it is evident that Lewandowski is Poland’s reference for their style. We expect Senegal to nullify Lewandowski’s treats and carry the day. Next up is Japan. In May 2018, Japan parted ways with coach Vahid Halilhodzic and appointed Akira Nishino. Vahid’s defensive style and fall out with players of the national team were the justifications given by the JFA for his sacking. Nishino promised a more attacking way of playing and with players like Kagawa, Okazaki and Honda, Japan are poised to give a good account of themselves. This is tricky but Senegal are the favourites to win this game. Senegal’s final game is against Colombia. Colombia’s attacking approach to the game is very difficult to deal with and with players like James Rodriguez, Juan Cuadrado, Radamel Falcao and Carlos Bacca Senegal will have to be at their best to avoid a defeat. A closer look at this group makes it very difficult to predict but we expect Colombia and Senegal to pull through. Senegal are also expected to go past the quarter-final stage which they achieved in 2002 and with a rich technical bench consisting of Tony Sylva, Omar Daf and Lamine Diatta who are all former players with so much experience in the game, Senegal must be really looked out for. This world cup could, after all, present itself as the perfect forest the long-starved Teranga Lions needs to nourish itself. firstname.lastname@example.orgFollow on twitter@kwabaid —Follow the World Cup with the Multimedia Group! 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