Leaky vaccines could lead to more virulent pathogens

In 2015, The National Chicken Council projected that consumers in the United States would eat more than 1.25 billion chicken wings during the 2015 Super Bowl. The Super Bowl represents the second largest “eating day” in the U.S., the first being Thanksgiving. Poultry is a staple food in the U.S., and also an important part of the culture of celebrating these two events. So when avian influenza, also known as “bird flu,” invades, the country goes on high alert.

Bird flu occurs naturally in wild waterbirds across the world, and these animals can be infected and not display any symptoms. Bird flu is very contagious among birds, and when these viruses reach the domestic bird population (e.g., chickens, ducks and turkeys) in places like the U.S., culling entire flocks of birds is a standard response. In a December 2015 report, the United States Department of Agriculture (USDA) said that the outbreak of avian influenza in the spring and summer of 2015 was the “worst animal disease outbreak in U.S. history.” This particular outbreak resulted in the “depopulation” (i.e., death) of more than 48 million domesticated birds. While all countries that raise bird populations for meat are at risk of avian influenza spreading within the flocks, the U.S. and the UK are different from some other countries in that domestic birds are not vaccinated for the avian flu.

The USDA has access to a small stockpile of avian flu vaccines to prevent the disease from developing among domesticated bird populations, but this tool has never been used, according to the USDA’s Animal and Plant Health Inspection Service (APHIS). The USDA notes that the currently available vaccine formulations “… reduce sickness, clinical signs (e.g., symptoms) and death in domestic poultry. [The vaccines] would not prevent birds from becoming infected with the [avian influenza] virus or from producing and shedding virus into the environment.”  In other words, the USDA is not deploying the available vaccines because they leak.

What makes a vaccine leaky?

According to Dr. Andrew Read, an evolutionary biologist at Pennsylvania State University (for full disclosure, I also work at the university) vaccines can function in two ways: a vaccine can be “perfect” (i.e., as perfect as we can make them) or it can be leaky.

Perfect vaccines will stop onward transmission of the virus while also providing immunity that mimics the result of the actual infection in the host. Perfect vaccines, such as immunizations against polio, measles and other childhood diseases (which are mandatory for children in the U.S.) produce immunity about 90 – 100% of the time by stopping the evolution of the pathogen, halting any transmission between hosts. A perfect vaccine will prevent a vaccinated individual from becoming sick and also prevents them from transmitting the virus to others.

A “leaky” vaccine gets its name because it forms a permeable layer in the host, allowing for some of the pathogens to transmit past this weak wall of protection. A leaky vaccine protects the host but continues to allow for the forward transmission of the disease. The immunizations that are currently being used in poultry against the bird flu are of the “leaky” type and research recently published in PLOS Biology demonstrates that these types of vaccines may make viruses more severe.

Making viruses more foul: Research shows leaky vaccines increase virulence in hosts

Read, the lead author of the PLOS Biology study, and his research team previously developed a mathematical model to test the theory that some vaccines could allow for virulence evolution, which refers to when extremely infectious versions of a virus survive in a vaccinated and seemingly healthy host. The findings reported in PLOS Biology by Read and colleagues show that the theory of virulence evolution has merit.

The research team found that the use of leaky vaccines in another bird-borne virus, Marek’s disease, can lead to the survival of more virulent strains of the virus. Marek’s disease is a herpesvirus of chicken that causes paralysis, eye lesions, tumors, and eventually death that is shed through chicken dander (or dust). In the 1930s, the virus didn’t kill enough birds to seriously concern the chicken industry, but by the 1960s, Marek’s began to affect flock size enough that the USDA started a program to vaccinate the birds. Early research on Marek’s vaccine established that it did not stop the forward transmission of the virus. In spite of evidence showing the Marek’s vaccine was leaky, the USDA did not slow their vaccination program and aimed to treat every chicken. Increasingly more virulent strains of Marek’s disease continued to be shed among chicken populations, and Read and his team proposed that the leaky vaccine could be providing the route for the virus’ evolution. Read and his team replicated this phenomenon by exposing vaccinated and unvaccinated chickens to Marek’s disease. Their work showed that an extremely virulent virus would kill an unvaccinated chicken before it was able to shed much of the virus, whereas birds that did receive the Marek’s vaccine were able to survive the infection while continuing to transmit the deadly pathogen.

The study proceeded as follows: Researchers infected both unvaccinated and vaccinated birds with the virus that causes Marek’s disease. Next, they introduced the infected population to a group of unvaccinated, uninfected chickens. In this experiment, the unvaccinated and uninfected chickens that were exposed to the infected, unvaccinated chickens did not get sick, and the infected hosts died before they were able to shed a substantial amount of virus. In contrast, the unvaccinated birds that were exposed to the vaccinated birds died. These findings support the team’s previously modeled theory — that leaky vaccines lead to transmission of a more virulent strain of a particular virus.

Read’s findings that leaky vaccines resulted in a more virulent strain of Marek’s disease in chicken populations may have implications for other infectious diseases that scientists aim to control with vaccinations in human populations. Read’s experiments with vaccinated and unvaccinated chickens introduces a new line of inquiry: Could the use of leaky vaccines for avian influenza (“bird flu”) lead to the evolution of a more virulent pathogen?

Vaccines need to be rigorously evaluated

Immunization is one of the most effective public health tools to protect against death and devastation from infectious diseases such as measles, mumps and polio; many of which have been eliminated from the United States through rigorous vaccination coverage as sanctioned by the CDC. The 2015 PLOS Biology study on Marek’s disease does not question the safety of vaccines currently used in human populations, but it does raise concerns that researchers need to be aware of when developing vaccinations for emerging diseases.

Bird flu has jumped the species barrier before; and vaccines that are being developed for use in humans, such as Ebola and malaria, are going to be the litmus tests. It is critical that these vaccines be evaluated and reevaluated rigorously as part of an ongoing process of building immune defense against these diseases. The ongoing threat of malaria and evolution of the Ebola virus in West Africa shows scientists that we cannot risk introducing a disease with evolving virulence through the widespread use of leaky vaccines.

References

Wikipedia: https://en.wikipedia.org/wiki/Avian_influenza

CDC: Avian Flu http://www.cdc.gov/flu/avianflu/avian-in-birds.htm

USDA Continues to Prepare for Any Possible Findings of Highly Pathogenic Avian Influenza: https://www.aphis.usda.gov/wps/portal/aphis/home/!ut/p/a1/04_Sj9CPykssy0xPLMnMz0vMAfGjzOK9_D2MDJ0MjDz9vT3NDDz9woIMnDxcDA2CjYEKIoEKDHAARwNC-sP1o8BKnN0dPUzMfYB6TCyMDDxdgPLmlr4GBp5mUAV4rCjIjTDIdFRUBADp5_lR/?1dmy&urile=wcm%3apath%3a%2Faphis_content_library%2Fsa_newsroom%2Fsa_stakeholder_announcements%2Fsa_by_date%2Fsa_2015%2Fsa_12%2Fct_hpai_preparedness

National Chicken Council: http://www.nationalchickencouncil.org/americans-eat-1-25-billion-chicken-wings-super-bowl-2/

USDA: Avian Influenza in the United States: http://www.usda.gov/documents/avian-influenza-united-states-qa.pdf

Influenza Activity — United States and Worldwide, 2003–04 Season and Composition of the 2004–05 Influenza Vaccine: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5325a1.htm

HPAI and Vaccine Use: https://www.aphis.usda.gov/publications/animal_health/2015/fs-hpai-vaccine-use.pdf

Additional Criteria Must Be Met Before Emergency Use of Vaccine for Highly Pathogenic Avian Influenza Can Be Approved, USDA Animal and Plant Health Inspection Service sent this bulletin at 06/03/2015 03:45 PM EDT: http://content.govdelivery.com/accounts/USDAAPHIS/bulletins/1079e08

Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens, Read, Andrew F.,  et. al., Published: July 27, 2015, DOI: 10.1371/journal.pbio.1002198 http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002198

Iowa Turkey Farmer “Living the Avian Influenza Nightmare,” National Turkey Federation, July 7, 2015, www.eatturkey.com/pressroom/iowa-turkey-farmer-%25E2%2580%259Cliving-avian-influenza-nightmare%25E2%2580%259D

Imperfect vaccines and the evolution of pathogen virulence, Sylvain Gandon, Margaret J. Mackinnon, Sean Nee & Andrew F. Read, Nature 414, 751-756 (13 December 2001) | doi:10.1038/414751a, http://www.nature.com/nature/journal/v414/n6865/full/414751a.html

The economics of Marek’s disease control in the United States, H.G. , Schultz, E.F. Jr., World’s poultry science journal 1978 v. 34 no. 4 pp. 198-204 http://naldc.nal.usda.gov/catalog/9304

Vaccine effectiveness: http://www.vaccines.gov/basics/effectiveness/

Presence and Survival of Marek’s Disease Agent in Dust, V. Jurajda and B. Klimes , Avian Diseases Vol. 14, No. 1 (Feb., 1970), pp. 188-190, Published by: American Association of Avian Pathologists  DOI: 10.2307/1588571, URL: http://www.jstor.org/stable/1588571