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.)
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
More on vaccines:
- Silk cages preserve vaccines and antibiotics for months without refrigeration
- Will we ever have an HIV vaccine?
- Herding HIV into an evolutionary dead end – study finds the virus’s weak spots
- Goodbye smallpox vaccination, hello monkeypox
- Genes from Arctic bacteria used to create new vaccines
- Vaccine against 2009 pandemic flu also protects mice against 1918 strain
Image by Jlastras