Momentum builds for cell-culture flu vaccines

first_imgJun 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.htmllast_img read more

Accurate social aid data still eludes government

first_imgThe government has committed to assisting citizens hit hardest by the COVID-19 outbreak until the end of the year, but persistent issues of data reliability have complicated efforts in the capital and other regions.In a recently published study by the SMERU Research Institute conducted between late April and mid-May in five cities and regencies of the country, researchers found instances where government social assistance ended up in the wrong hands.The study found that 400 of the 2,000 listed recipients surveyed in a certain district should have been ineligible for aid, either because they had escaped poverty or were already deceased. The study did not specify which region this data was from.Jakarta began its social assistance program on April 9 and committed to support the 2.2 million households most affected by the COVID-19 outbreak. The program, which will continue to disburse monthly aid until December, involves the central government, which has committed to supporting the majority of potential recipients, roughly 1.3 million people.Pepen Nazarudin, the Social Affairs Ministry’s director general for social empowerment, said the number of recipients was fixed and could not be changed. He said it was the city administration’s responsibility to determine which recipients should be prioritized.Early on in the program, the lack of reliable recipient data caused a number of logistical problems, including mistargeted aid, which Jakarta Governor Anies Baswedan complained about in April. After four months of running the program, the city has seen improvements in its services, although shortcomings remain.“Social aid disbursement for stages two to four [conducted from May to mid-July] has reached 100 percent, which means that all of the assistance has been disbursed,” said Ika Yuli Rahayu, the Jakarta Social Agency’s head of social security protection, on Wednesday.Ika acknowledged that some ineligible recipients had been discovered during the disbursement process and that local authorities usually looked for the next eligible person to give the aid to.“There were still one or two [ineligible recipients] that we found, but this didn’t occur in every subdistrict,” she said.The official said that when the recipient was deceased or had been registered to the wrong address, the next recipient would be determined based on the recommendation of the neighborhood unit (RT), community unit (RW) or subdistrict head.People who were not registered as recipients but were eligible for social assistance could also be considered, she said.Jakarta RT/RW Forum chairman Muhammad Irsyad said that human error was one reason why aid still ended up with ineligible recipients despite an updated database.Jakarta Deputy Governor Ahmad Riza Patria said last month that data problems had occurred because different institutions employed different methods to process recipient information.But Irsyad also said that the implementing authorities had improved since the early days of the program and that officials would try to quickly resolve outstanding cases.“There is no more of the turmoil that we experienced at the outset,” he said.The National Development Planning Agency (Bappenas) recently revealed that only 113 of the country’s 514 municipalities and regencies had updated their data on the Social Affairs Ministry’s Integrated Data for Social Welfare (DTKS) site, a database of poor and vulnerable families.The regions with updated data were predominantly located on the island of Java, as well as the Bangka Belitung islands and Nusa Tenggara.Semarang in Central Java, Bojonegoro in East Java and Pariaman in West Sumatra were among the few other regions that had provided new data, Bappenas director of poverty alleviation and social welfare Maliki told The Jakarta Post.In Jakarta, some municipalities have managed their data well, but that data’s accuracy – whether the listed recipient is eligible in real life – is a different topic altogether, Maliki said.The government relies on the National Social and Economic Survey (Susenas) to evaluate data accuracy. “The Susenas in September of this year will be a good opportunity to evaluate the accuracy of social aid programs, as the survey will include disbursements for the previous four months,” he said.About 1.63 million Indonesians fell into poverty between September 2019 and March of this year as the COVID-19 outbreak took a toll on the nation’s poor, Statistics Indonesia (BPS) data shows.Jakarta recorded that 1.11 percent of its population had fallen into poverty, the highest percent increase of any province. Now, 4.53 percent of its citizens are considered poor.“Jakarta’s poverty rate is the highest in the past decade and even approaches Jakarta’s condition 20 years ago [4.96 percent],” the Jakarta Statistics Agency wrote.In addition to social assistance for poor families in the capital, the city administration has also distributed staple food to people thought to have the illness and people who are self-isolating in RWs declared “red zones”.More than 6,000 families from the 48 subdistricts in mainland Jakarta and the four islands of the Thousand Islands that had been declared red zones as of July 13 were listed as eligible recipients of social assistance.Topics :last_img read more

Research continues into fungus affecting Dominica’s crapaud population

first_imgLive mountain chicken (GIS photo)ROSEAU, Dominica (GIS) — Forestry officials in Dominica are working with counterparts at the Zoological Society of London to determine the cause and eventually bring an end to the crisis, which has resulted in a significant decline in the population of the island’s mountain chicken.Professor Andrew Cunningham of the Zoological Society of London has been monitoring the decline of the crapaud population since it began in 2002.He said on Tuesday that, due to the unique nature of this species of frog, researchers are very concerned about the declining population.“The mountain chicken is a really important species. It is the second largest frog in the whole world and has an amazing life cycle. The reproduction of this frog is unlike any other species. The female will prepare a full nest in a burrow in the ground and she lays her eggs in that next. When they hatch, the tadpoles stay underground in that nest and the female comes and feed the tadpoles with infarcted eggs that she passes herself. When they metamorphose and turn into small frogs, the female continues to look after them for a number of days after they leave the burrow. So this is a really interesting reproductive strategy but the mountain chicken, being one of the largest frogs in the world, is a very important predator of invertebrates on Dominica and in Montserrat. They feed on a huge number of crickets and millipedes and agricultural pests. Therefore, they are a very important for the ecology of the island and for human wellbeing as well,” he explained.Early in 2002, dead crapaud were found in various parts of the island and their friendly calls slowly faded. After extensive examinations researchers determined the cause of their deaths.“A fungus, called Chytrid fungus, appeared to have been introduced into Dominica. We do not know how it got here but it started to kill the crapaud. By 2004, the population of crapaud on Dominica had declined by over 80 percent. So, only two in ten animals are left alive. Since 2004, that decline continued at least until a couple of years ago to the point the animal was almost completely wiped out across the whole island,” Cunningham said.The Chytrid fungus however did not only affect the crapaud population.“This fungus is causing problems for other species of amphibians across the world; in North and South America, Africa, Australia and in Europe, this fungus is spreading. We think it started to spread in the 1960’s and it has been causing many different species of frogs and toads and salamanders to decline. It kills them and the populations decline very rapidly. We think about a hundred species have gone extinct in the last twenty to thirty years purely because of the spread of this fungus,” he added.Researchers are still trying to determine how the fungus was introduced into Dominica’s forests.“There is quite a lot of research going into that not just with the mountain chicken but with other species that have been hit hard with this fungus. Some species of frogs do not appear to be affected by the fungus and the ‘gounouge’ here in Dominica is one of those species (those little tree frogs). They are as numerous as they have ever been on the island and yet we know they can be infected by this fungus. Indeed, some of them seem to be carriers of the fungus so they are infected but not killed by it,” Cunningham said.In an effort to replace the dying crapaud population a captive breeding programme has been introduced at a special facility within the botanic gardens.“From here, the main thing is to see if we can breed the animals in captivity in Dominica and if we can, we will then start a release programme similar to the one that has, so far, at least been successful in Montserrat. But this time, we will be using captive bred animals from within the country rather than bring them back from overseas. They will be Dominican frogs through and through and we will then be releasing them, assuming that we are successful in breeding, back into their natural habitat on the island. The animals will be tagged with a transmitter so that we can follow them knowing where they go and how they survive. If they do get infected by the fungus, we should be able to detect if that is happening or if they are able to survive or if they move to new areas, we should also be able to detect if that is happening. But, this is some way into the future because at the moment we still have to breed the animals here in Dominica,” he outlined.It is difficult to determine when the crapaud population will once again begin to live within the island’s forests but Cunningham is confident that it will happen.“It is a very iconic species for Dominica. What will the Nature Isle be like without its nature? It is really important that we all make a big effort over the next few years to conserve the species and hopefully try to get the numbers back up through captive breeding, through protection in the wild and so on so that one day again, people can eat the national dish of Dominica. But that is not going to happen for a little while I am afraid,” he said.By Mervin MatthewSource: Caribbean News Now LocalNews Research continues into fungus affecting Dominica’s crapaud population by: – August 22, 2011 Share Share 149 Views   no discussionscenter_img Tweet Share Sharing is caring!last_img read more