Are vaccines making viruses more dangerous?

Despite the near-universal acceptance of the benefits of vaccination, some people still worry about risks associated with their use. Luckily, scientists are vigilant about identifying possible risks, so they can be addressed before problems emerge.

Still, people sometimes forget that science is the process by which we arrive at solutions. And they worry about incremental scientific steps that often expose weakness in these solutions.

A recent study published in the journal PLOS Biology, for instance, was presented by some media as claiming that certain vaccines make viruses more dangerous. The research showed chickens treated with its vaccine are more likely to spread a highly virulent strain of Marek’s disease virus, a condition that affects poultry.

The reason was simple: the vaccine used in the study targets Marek’s disease, not the virus that causes it. These types of vaccines are known as “leaky vaccines” because they don’t affect the ability of the virus to reproduce and spread to others; they simply prevent the virus from causing disease.

Marek’s disease vaccines use a non-disease-causing virus to infect cells. This preventive infection stops tumour formation and death when those cells are infected by the Marek’s disease virus.

But the virus can replicate and still produce more virus particle, which can infect other chickens. All Marek’s disease vaccines, since their introduction in the 1970s, have been leaky; they allow chickens to carry and spread the virus without getting the disease.

‘Imperfect-vaccine hypothesis’

The effect of leaky vaccines on how disease spreads is explained by the “imperfect-vaccine hypothesis”. It holds that, without vaccination, a very virulent virus can get into a population and kill infected hosts (people or animals) very quickly – before they have a chance to spread it. This means that the virus will die out very quickly too, as all potential hosts will be dead or immune to it.

A leaky vaccine can prevent the very virulent virus from killing the host, but doesn’t stop that host from spreading the virus to others. This means that a very virulent virus can survive for long periods in the vaccinated hosts. And it can continue to spread in this time, making it less likely to die out.

The PLOS Biology study showed chickens vaccinated against Marek’s disease were more likely to spread the disease to other chickens, than unvaccinated chickens were. The unvaccinated chickens all died in less than ten days – before they could spread the virus.

The vaccinated chickens, on the other hand, were protected from the disease so were able to spread the virus to other (unvaccinated) chickens for weeks and weeks. And they made those chickens immune to the virus in the process.

Marek’s disease, which affects poultry, has a ‘leaky’ vaccine'.David Goehring/Flickr, CC BY-SA

One of the reasons the researchers looked at Marek’s disease in chickens is because it has been getting progressively deadlier. Originally, the disease occurred mainly in older chickens and caused paralysis. But an acute form of the disease emerged in the 1950s and has since become the dominant form. This rather virulent version can kill up to 100% of unvaccinated birds.

Leaky but not sinking

But what does all this mean for the future of vaccination?

Well, the first thing to note is that in this study the vaccinated chickens always had the best outcome. In one experiment, only three out of 50 unvaccinated chickens survived the disease, while vaccination protected the majority of chickens (46 out of 50 survived).

The authors also noted that vaccination has been very effective in preventing deaths in chickens due to Marek’s disease. They said their study didn’t indicate whether vaccination played any role in the development of the serious form of Marek’s disease.

Vaccines prevent disease, even if they’re leaky. But it’s important to note there are currently no vaccines against viruses that infect humans that are leaky. Current human vaccines mimic the body’s own response to viruses.

But yet-to-be-developed vaccines for diseases such as HIV, Ebola or malaria, where humans have been unable to mount an effective natural defence, are likely to be leaky. And even imperfect vaccines for these illnesses would be an enormous step forward.

The possible effect of “leaky vaccines” on how viruses spread is an interesting new observation. But there are a number of other ways by which viruses can change in response to vaccination.

An arms race

One response of viruses to vaccines involves the evolution of viral proteins that allow them to escape the vaccine. This is known as “epitope evolution” and it’s the reason flu vaccines change each year.

Even if a vaccine is effective in preventing a particular strain of virus, other strains may take its place. This was a concern when the human papillomavirus (HPV) vaccine was introduced nearly ten years ago. But researchers have investigated whether any HPV types not in the vaccine have become more common since the vaccine was introduced and there’s no evidence this is happening.

The interaction between viruses and their targets can change over time. In the case of Marek’s disease, the infection has become progressively deadlier. Increased use of broiler chickens, lack of genetic diversity in flocks and high-density rearing may all have played a role in the changes seen in the disease.

The benefits of vaccination far outweigh its risks. And it is research like this that helps medical researchers actively identify possible dangers so we can safely continue to avoid the diseases that terrified our parents' generation.

Dave Hawkes has previously received funding from NHMRC and the Name the Virus crowdfunding campaign.