first_img To achieve prepandemic vaccines, researchers would have to ascertain the right dose and dose interval, determine how long priming lasts, and solve the puzzle of measuring primed immunity. Further, regulatory authorities would have to determine the trial design that could deliver those answers, the public discussion that would be necessary for prepandemic vaccines to be accepted, and the safety data that would need to be gathered once the vaccines went into use (see Bibliography: Goodman 2007). A number of the studies that have shown adjuvants may be able to stretch the vaccine supply also demonstrated a secondary benefit: The formulas protected not only against the H5N1 flu strain on which they were based, but against other H5N1 strains as well, a phenomenon called cross-reactive protection (see Bibliography: Nicholson 2001, Stephenson 2005, Govorkova 2006, Hehme 2007, Hoffenbach 2007). Most recently, the GlaxoSmithKline-backed team that described an acceptable immune response after two adjuvanted 3.8-microgram (mcg) doses found that three fourths of their subjects were protected not only against the clade 1 Vietnam virus on which the vaccine was based, but against a drifted clade 2 virus from Indonesia as well (see Bibliography: Leroux-Roels 2007). “I think priming should be done, but I am not sure how it should be done,” said Dr. John Wood, principal scientist in the division of virology at the United Kingdom’s National Institute for Biological Standards and Control. “What we don’t know is how low you can go to actually prime people. It may be that you can go much lower than where we can detect antibody. That is a regulatory headache, because you have to demonstrate that you are doing something, but there is a potential there” (see Bibliography: Wood 2007: author interview). At the moment, however, the science is thin. Much of the support for priming has come from animal studies (see Bibliography: Lipatov 2005, Govorkova 2006, Kreijtz 2007) or via computer modeling (see Bibliography: Longini 2005, Ferguson 2006, Germann 2006). A few small studies in humans have shown promising results. In one, serum from 15 volunteers who received three doses over 16 months of an adjuvanted vaccine based on a 1997 H5N3 isolate showed significant antibody response against H5N1 strains isolated years later (see Bibliography: Stephenson 2005). In another, 37 participants who had been given a baculovirus-grown, clade 3 H5 vaccine in 1998 were boosted with a single dose of the unadjuvanted 90-mcg Sanofi vaccine in 2005, and showed much higher antibody responses than participants who had not been primed but received one or two doses of the 90-mcg vaccine (see Bibliography: Treanor 2007: Immune responses). And researchers at a conference earlier this year reported that some of the participants in the phase 3 trial of the 90-mcg Sanofi vaccine were boosted with a third dose 6 months after their second dose and showed a significant rise in antibody levels that lasted for 6 months (see Bibliography: Zangwill 2007). A tough ethical problemBut the next logical step—that if vaccines can be formulated without waiting for a pandemic, they could be administered before a pandemic began—is a much tougher one to take, and policy makers are approaching it with great caution. The scientific, logistical, and especially ethical questions raised by prepandemic vaccination are grave. “Extraordinary threats call for consideration of innovative strategies that, in less-threatening circumstances, might be dismissed,” Bruce Gellin and Ben Schwartz of the Department of Health and Human Services’ National Vaccine Program Office wrote 2 years ago. “Although it has been assumed that pandemic vaccine cannot be stockpiled or that vaccination cannot occur before the start of a pandemic, might these approaches actually be possible? . . . Would receipt of a vaccine prepared before the pandemic be effective in providing some protection or in priming recipients so a single subsequent dose of vaccine would be protective?” (see Bibliography: Schwartz 2005). The danger demonstrated by both those campaigns, of causing adverse events while protecting against a disease that might never arise, has been noted in World Health Organization (WHO) policies as well. “Possible high-risk shortcuts in response to a potential emergency would be difficult to justify prior to the actual occurrence of the emergency,” the agency said after the June 2006 meeting of its Global Advisory Committee on Vaccine Safety. “Effectiveness of pandemic vaccines will not be known before the pandemic and possibly only after it is over” (see Bibliography: WHO 2006: Global Advisory Committee on Vaccine Safety, 6-7 June 2006). The prime-boost strategyThe most likely and biologically plausible use of prepandemic vaccination would be as the first half of a “prime-boost” series. People would still be given the two doses of vaccine necessary to provoke immunity in a naïve individual. But the doses would be based on different vaccine strains—the first an early best guess, the second tuned to the pandemic strain—and could be given not weeks but months or years apart if the science supported it. Yet the potential benefits of prepandemic vaccination are so alluring that governments have begun gingerly to lay groundwork for its consideration, despite the obvious difficulties of putting the idea into practice. The findings are not completely understood, though researchers agree that they make biological sense. Adjuvants stimulate the immune system in some manner that is broader than and different from the body’s reaction to the antigen packaged with them. The discovery that adjuvanted flu vaccines may invoke cross-reactivity has generated tremendous excitement—because that could allow production of at least partially protective vaccines well in advance of a pandemic’s beginning. Part 1: Flu research: a legacy of neglectPart 2: Vaccine production capacity falls far shortPart 3: H5N1 poses major immunologic challengesPart 4: The promise and problems of adjuvantsPart 5: What role for prepandemic vaccination?Part 6: Looking to novel vaccine technologiesPart 7: Time for a vaccine ‘Manhattan Project’?Bibliography Hurdles are manySo many steps separate those early results from an agreed-upon policy that would allow for prepandemic vaccines—in an annual flu shot or stockpiled until the WHO declares a pandemic imminent—that it is unrealistic to expect them to be created any time soon. The scientific questions alone are significant and novel. Any vaccination that took place before a pandemic was detected would offer uncertain amounts of both benefit and risk. The vaccine might be cross-protective against a future pandemic—but the lag time to the pandemic’s emergence might be so long that the vaccination would seem pointless. As well, the vaccine might cause a greater-than-expected rate of adverse events, causing both direct harm to recipients and indirect damage to government credibility—results that would be particularly difficult to tolerate if vaccination proved unnecessary because the pandemic did not arrive. Those risks are not theoretical: They have been demonstrated in the United States twice in recent history, in the abortive 2002 smallpox vaccination campaign and the 1976 swine-flu campaign (see Bibliography: Kotalik 2005), which has haunted US flu decision-making ever since. Editor’s note: This is the fifth in a seven-part series investigating the prospects for development of vaccines to head off the threat of an influenza pandemic posed by the H5N1 avian influenza virus. The series puts promising advances in vaccine technology in perspective by illuminating the formidable barriers to producing large amounts of an effective and widely usable vaccine in a short time frame. Part 4 examined the possibility of using adjuvants to stretch the supply of pandemic vaccines and the regulatory barriers to that strategy. Recognizing those hurdles, the European Centre for Disease Prevention and Control said in August that while it welcomes the development of prepandemic vaccines, it would not support administering them until a WHO declaration of pandemic phase 5 or 6, meaning significant human-to-human transmission is occurring or a pandemic is under way (see Bibliography: ECDC 2007: “Pre-pandemic” vaccines might offer protection but uncertainties remain). The pandemic vaccine puzzle Oct 31, 2007 (CIDRAP News) – Experiments with vaccine adjuvants have raised some hope of removing one of the great stumbling blocks to pandemic influenza preparedness: the impossibility of making a vaccine that protects against a pandemic virus before that virus actually emerges. last_img read more

first_imgThis house, named Laurent, at 44 Reading St, Paddington, was designed by Joe Adsett and recently sold for nearly $4m. Picture: Scott Burrows. BEFORE: The front of Brisbane architect Joe Adsett’s house at 18 Kitchener Rd, Ascot, before he redesigned it. Photo: BEFORE: Brisbane architect Joe Adsett’s house at 18 Kitchener Rd, Ascot, before he redesigned it. Photo: AFTER: The new indoor/outdoor living area after the house was redesigned.The house is almost finished, but Mr Adsett said it would take another few months for the finishing touches to be made to the fit-out.More from newsParks and wildlife the new lust-haves post coronavirus12 hours agoNoosa’s best beachfront penthouse is about to hit the market12 hours agoRecords show Mr Adsett and his wife, Hayley, bought the property for $2.665 million in November, 2017. MORE: Broncos skipper signs new agent Joe and Hayley Adsett with their son Julian. They now have two children. Picture: Claudia Baxter.It was originally a mid-century home on a huge 1200 sqm block comprising three lots, but has now been transformed into a three-level, six-bedroom masterpiece with the help of Graya Construction.“There was a lovely house there, but it was just orientated in the wrong direction and we just couldn’t work with it,” Mr Adsett said.“We’ve certainly designed it to be very particular to our own brief.“I’ve designed houses for myself which were stepping stone houses, but this was really looking at the 10 year play.” BEFORE: The living area leading to an outdoor balcony at Brisbane architect Joe Adsett’s house at 18 Kitchener Rd, Ascot, before he redesigned it. Photo: AFTER: The kitchen in the house after it was redesigned.With two kids aged three and five, Mr Adsett said he and his wife wanted a family home.“It’s not designed to be a trophy house — it really is a family home,” he said.“It is a big house, there’s no mistake about that, but it’s designed for lifestyle.”The Adsetts spent a few years looking for the right property before they found 18 Kitchener Road.“We really wanted a block of land that was elevated, flat, large and a square block,” Mr Adsett said.“It’s very rare to find a big, square block. Rectangular blocks are limiting, whereas a square block allows for these types of houses.” The new Boyd residence, as envisioned by Joe Adsett, will be built by Graya Construction. Source: Facebook/Graya.But for the past year, Mr Adsett has been working on his biggest project yet — his dream home in Ascot called ‘Boomerang’ after its signature ‘L’ shape.The three-level home is currently being filmed to appear on the Foxtel television series ‘Grand Designs Australia’.“When you’re advising for clients or a developer, it’s very easy to be objective and … make decisions, but when it’s yourself you can sit there and say; ‘what is it I actually want?’” Mr Adsett said.“I could do it 10 different ways — which way do I like the best?”center_img AFTER: An aerial shot of the house at 18 Kitchener Rd, Ascot, before it was redesigned. Photo: BEFORE: The outdoor area at the original house. Photo: The house at 18 Kitchener Road after the rebuild.ARCHITECT JOE ADSETT’S TIPS FOR MAKING A HOUSE A HOME*Orientation – design the living spaces to face north-east*A flexible floorplan – the Adsett house has six bedrooms, but all could be converted to other spaces if preferred*Privacy – Separate the master bedroom from the kids’ bedrooms*Man cave – a big garage underneath the house*Emphasis on family lifestyle – indoor/outdoor living areas to make the most of Brisbane’s climate and put pools and tennis courts close to the house so that they are easy to access. AFTER: The front of Brisbane architect Joe Adsett’s house after he redesigned it.Other recent projects include ‘Laurent’ at 44 Reading St, Paddington, which recently sold for $3.98 million, a house on a 215 sqm block in Small St, Teneriffe, which fetched $1.9 million despite the tiny lot and another property at 192 Baroona Rd, Paddington, which has just gone under contract for $2.35 million. Brisbane architect Joe Adsett’s new house at 18 Kitchener Rd, Ascot.HE has designed showstopping houses for some of Queensland’s fussiest clients, but Joe Adsett’s toughest brief yet has been his own. As one of Brisbane’s leading architects, Mr Adsett is renowned for bringing Queenslander homes into the 21st century with his multimillion-dollar, contemporary creations for high profile clients.He is currently designing a new dream home for NRL star Darius Boyd and his wife, Kayla, that will be minutes from Suncorp Stadium. RELATED: Buyers swooping in to snap up dream homes fast AFTER: The outdoor area and tennis court at the new house.The ‘L’ shape of the house is a trend Mr Adsett has been incorporating in many of his new projects because of the emphasis it places on indoor/outdoor living.“It’s a very classic kind of style,” he said.“The Romans were doing courtyards, so it’s been around a long time, but definitely the contemporary interpretation of these kind of old housing forms is something we look to run with.“We’ve gone with a lightweight timber box floating over a stone base and the upper level is really light like a nest.”Intricate baton work has been used to recreate the Queenslander style.Mr Adsett said his wife, Hayley, had been instrumental in helping him design their dream home. “So many of the decisions around the materials and the experience of the house have come from her input,” he said.last_img read more