Scientific experiments with the herpes virus strain that causes Marek's disease in poultry have confirmed, for the first time, the highly controversial theory that some types of vaccines allow for the evolution and survival of increasingly virulent versions of a virus, putting unvaccinated individuals at greater risk of severe illness. The research has important implications for food-chain security and food-chain economics, as well as for other diseases that affect humans and agricultural animals.

The new research, which will be published in the Open Access journal PLOS Biology on July 27th, investigates how the use of "leaky" or "imperfect" vaccines can influence the evolution of virulence in viruses. The work was carried out by an international group led by Prof. Andrew Read, the Evan Pugh Professor of Biology and Entomology and Eberly Professor in Biotechnology at Penn State University, USA and Prof. Venugopal Nair, the Head of the Avian Viral Diseases programme at The Pirbright Institute, UK.

Imperfect, or leaky, vaccines are known as such because they prevent the vaccinated host from getting sick but do not prevent the transmission of the virus, thus the virus is able to survive and to spread throughout a population. "In our tests of the leaky Marek's disease virus in groups of vaccinated and unvaccinated chickens, the unvaccinated died while those that were vaccinated survived, and transmitted the virus to other birds left in contact," Nair said. "Our research demonstrates that the use of leaky vaccines can promote the evolution of nastier 'hot' viral strains that put unvaccinated individuals at greater risk."

"When a vaccine works perfectly, as do the childhood vaccines for smallpox, polio, mumps, rubella, and measles, it prevents vaccinated individuals from being sickened by the disease, and it also prevents them from transmitting the virus to others," Read said. These vaccines are "perfect" because they are designed to mimic the strong immunity that humans naturally develop after having been exposed to one of these diseases. "Our research demonstrates that another vaccine type allows extremely virulent forms of a virus to survive -- like the one for Marek's disease in poultry, against which the poultry industry is heavily reliant on vaccination for disease control," said Prof. Nair. "These vaccines also allow the virulent virus to continue evolving precisely because they allow the vaccinated individuals, and therefore themselves, to survive".

"Vaccines for human diseases are the least-expensive, most-effective public-health interventions we ever have had," Read said. "But the concern now is about the next-generation vaccines. If the next-generation vaccines are leaky, they could drive the evolution of more-virulent strains of the virus." He said it is critical now to determine as quickly as possible that the Ebola vaccines that now are in clinical trials are not leaky -- that they completely prevent the transmission of the Ebola virus among people. "We do not want the evolution of viral diseases as deadly as Ebola evolving in the direction that our research has demonstrated is possible with less-than-perfect, leaky vaccines," Read said.

He also recommends vaccination for individual protection. "When evolution toward more-virulent virus strains takes place as a result of vaccination practices, it is the unvaccinated individuals who are at the greatest risk. Those who are not vaccinated will be exposed, without any protection, to the hottest strains of a virus. Our research provides strong evidence for the importance of getting vaccinated."

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All works published in PLOS Biology are open access, which means that everything is immediately and freely available. Use this URL in your coverage to provide readers access to the paper upon publication: http://www. plosbiology. org/ article/ info:doi/ 10. 1371/ journal. pbio. 1002198

Contact:

Dr Andrew Read

Penn State University

a.read@psu.edu

814 321 5004

Citation:

Read AF, Baigent SJ, Powers C, Kgosana LB, Blackwell L, Smith LP, et al. (2015) Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens. PLoS Biol 13(7): e1002198. doi:10.1371/journal.pbio.1002198

Funding:

This work was funded by the Institute of General Medical Sciences, National Institutes of Health (R01GM105244) and by UK Biotechnology and Biological Sciences Research Council as part of the joint NSF-NIH-USDA Ecology and Evolution of Infectious Diseases program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests:

The authors have declared that no competing interests exist.

Video: https:/ / psu. box. com/ Read7-2015