Chicken vaccines merged to form live viruses and caused outbreaks of irony
Since 2008, Australian chickens have been suffering from intense outbreaks of a disease called infectious laryngotracheitis (ILT). Their eyes become red and swollen, they cough and gasp for air, and they sometimes bleed from their noses. The survivors produce fewer eggs, leading to severe losses for farmers.
The disease is caused by a highly contagious virus called ILTV. It’s a herpesvirus, one of the group that causes herpes, chickenpox, and glandular fever in humans. It’s a problem for poultry the world over, but the recent outbreaks in New South Wales and Victoria have been unusually severe, killing up to 18 per cent of infected chickens. They also have an ironic origin – they’re the result of vaccines.
Chickens are often vaccinated against ILTV, using weakened versions of the virus. Now, Sang-Won Lee from the University of Melbourne has found that two such vaccines have merged together to create the live and virulent virus behind the recent outbreaks. The measures that were meant to protect the chickens have only made things worse. (Some of you may now be worrying or wondering if the same applies to human vaccines. You can skip straight to the end where I discuss this, but it’s worth knowing what actually happened first.)
Vaccine merger
For years, Australian farmers had used two vaccines called SA2 and A20, manufactured by Pfizer and based on local Australian ILTV strains. In 2006, a third vaccine called Nobilis entered the market – it was made by Intervet and used a European ILTV strain.
Last year, Hayley Blacker from the University of Melbourne showed that the new Nobilis vaccine might have been responsible for the recent outbreaks. The timing fit – the outbreaks happened shortly after the vaccine was introduced. Genetics strengthened the case. Blacker showed that the outbreak strains belonged to new branches of the ILTV family tree (classes 8 and 9) which were very similar to the strain in the Nobilis vaccine (class 7).
But Nobilis the only culprit. Lee discovered the true origins of the class 8 and 9 viruses by sequencing their entire genomes, along with those of the three vaccine strains. He found that while the outbreak strains are mostly related to the Nobilis one, they also carried genetic material from the SA2 and A20 strains.
By using multiple vaccines in the same animals, the farmers acted as matchmakers for the intercontinental viruses. The weakened Australian and European strains infected the same cells, “mated” with each other, and shuffled their genetic material (the technical term is “recombined”). Each individual strain was weakened by different mutations – different changes to their genes. When the strains merged, and their genes shuffled, they produced hybrids that lost all of these mutations, and could resume their normal virulent lifestyles. They proved to be far better at causing disease than either of their parents.
“A number of lab studies have shown herpesviruses can recombine under experimental conditions but previously, it was considered very unlikely that two vaccine strains would recombine in the field,” says Joanne Devlin who led the new study). People thought it unlikely that two weakened viruses of different strains would infect the same cell – a necessary step if their genes are to mingle. Devlin’s study shows that such an event might be rare, but it can happen, and with severe consequences.
This isn’t the only instance of poultry vaccinations backfiring. Vaccines have also been used to control bird flu outbreaks around the world. In countries where they were used carefully and efficiently, like Hong Kong and Vietnam, outbreaks were successfully controlled. But in other parts of the world, like Egypt and Indonesia, people used a number of different vaccines, and applied them messily. They didn’t check whether the treated birds were actually protected from the virus, or whether they harboured infectious individuals among them.
As a result, the virus wasn’t eradicated, and gained a proper foothold. It was also under intense pressure to evolve and soon gave rise to new genetically distinct lineages. Indeed, Ilaria Capua found that the virus had evolved faster in countries that used H5N1 vaccines compared to those that didn’t.
The message from these examples isn’t that animal vaccines are bad or dangerous. It’s that if they’re to be used, they need to be used appropriately. Careless vaccination of poultry will make matters worse. Likewise, using many distinct strains of live vaccine may not be the best idea either. “In Australia, the Australian Pesticides and Veterinary Medicines Authority is already reviewing the labels of the vaccines involved in order to change the way that they are used and prevent recombination,” says Devlin.
Is there a risk with human vaccines?
These problems are unlikely to apply to human vaccines. “Using more than one live vaccine at the same time is a feature of veterinary medicine rather than human medicine,” says Devlin.
Vincent Racaniello, a virologist from Columbia University, isn’t worried about the threat to human health either. “It’s good to know that recombination leading to the production of virulent vaccines can occur, and we should be sure that vaccines do not have the propensity to do this,” he says. “But the danger posed by recombination is far less than the harm that would be caused by acquiring the infection. In the world of vaccines, you always have to balance the benefits versus the risks.” He helpfully went through the various possibilities.
The measles, mumps and rubella (MMR) vaccine uses live but weakened viruses, but it only uses one strain of each, and they don’t recombine with one another. The chickenpox vaccine also uses weakened virus but again, it only uses a single strain. One flu vaccine, Flumist, uses two different strains of flu: H1N1 and H3N2. However, these have been hobbled by the same mutations, so even if they recombine, all of their progeny will still be crippled.
A vaccine against adenoviruses, which cause airway infections, consists of two weakened strains that could potentially recombine. But this vaccine is only given to the US military, and Racaniello says that a recombined virus wouldn’t likely cause more severe disease than what the vaccine is designed to prevent.
The polio vaccine is a slightly different story – the oral version consists of three strains of live viruses, which do recombine inside a patient and sometimes produce infectious viruses. This happens very rarely (around 1 in every 750,000 vaccinations), but when it does, it can lead to vaccine-derived polio. These isolated outbreaks will be contained if most of the world is immunised against polio, and they’d never happen at all if the disease was finally eradicated. Ironically, it’s when vaccinations wane that vaccine-derived polio becomes a problem.
Reference: Lee, Markham, Coppo, Legione, Markham, Noormohammadi, Browning, Ficorilli, Hartley & Devlin. 2012. Attenuated Vaccines Can Recombine to Form Virulent Field Viruses. Science http://dx.doi.org/10.1126/science.1217134
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질병 예방 백신의 ‘무서운 결합’
닭에 접종한 두 종류 백신이 치명적 바이러스 탄생시켜
조선비즈 | 이영완 기자 | 입력 2012.07.18 03:10
질병을 예방하려고 접종한 백신이 오히려 치명적인 바이러스를 만들어냈다. 호주 멜버른대 연구진은 ‘사이언스’ 최신호 논문에서 “닭에게 접종한 두 종류의 백신이 몸 안에서 서로 결합해 치명적인 바이러스로 탈바꿈했다”고 발표했다.
실험실에서 독성이 없는 두 바이러스를 일부러 결합, 새 질병 바이러스를 만든 경우는 있었다. 하지만 자연 상태에서 이런 일이 발생한 것은 처음이다. 호주 동물 방역 당국은 급히 대책 마련에 나섰다.
백신은 죽은 바이러스를 이용하는 ‘사(死)백신’과, 죽이지는 않고 질병 유발 인자만 없앤 ‘생(生)백신’으로 나뉜다. 백신 접종은 약한 병원균을 집어넣어 인체의 면역기능을 높이는 원리다. 예를 들어 방어군인 면역세포가 가상 적군인 백신 바이러스를 만나 군사훈련을 하는 것과 같다. 나중에 실제 병원성 바이러스가 침입하면 면역세포는 훈련받은 대로 바로 전면 공격에 들어갈 수 있다.
이번에 문제가 된 것은 후두기관지염 예방 생백신이었다. 닭이 이 병에 걸리면 20%가 죽는다. 호주에서는 40여년간 호주산(産) 바이러스로 백신을 만들어 접종했는데, 백신 공급이 부족하자 2006년부터는 유럽산 바이러스로 만든 백신까지 수입했다. 그런데 이듬해부터 백신 접종을 했는데도 후두기관지염이 번지기 시작했다.
멜버른대 연구진은 감염된 닭을 분석해 전혀 새로운 형태의 치명적 바이러스 두 종을 발견했다. 이 바이러스는 호주산 백신과 유럽산 백신에 쓰인 바이러스의 유전자를 짜깁기한 형태였다. 멜버른대 아시아·태평양 동물보건센터의 이상원 박사는 “유전자 재결합으로 탄생한 새 바이러스는 기존의 바이러스보다 더 심각한 질병을 일으키고, 복제도 쉽게 되는 것으로 나타났다”고 밝혔다.
호주 방역 당국은 연구결과를 통보받고 동일한 지역에서 원산지가 다른 두 백신을 접종하지 않게 하는 등 대책을 마련 중이다. 생백신은 주로 동물에게 쓰지만 사람에게도 간혹 사용하는 경우가 있다. 연구진은 “생백신이 체내에서 재결합해 치명적 무기가 될 가능성도 감안해야 한다”고 밝혔다.
