TWiV 373: The distinguished virology career of Julius S. Youngner

On episode #373 of the science show This Week in Virology, Vincent speaks with Julius about his long career in virology, including his crucial work as part of the team at the University of Pittsburgh that developed the Salk inactivated poliovirus vaccine.

You can find TWiV #373 at Or you can watch the video below.

The switch from trivalent to bivalent oral poliovirus vaccine: Will it lead to polio?

bivalent OPVIn four months, 155 countries will together switch from using trivalent to bivalent oral poliovirus vaccine. Will this change lead to more cases of poliomyelitis?

There are three serotypes of poliovirus, each of which can cause paralytic poliomyelitis. The Sabin oral poliovirus vaccine (OPV), which has been used globally by WHO in the eradication effort, is a trivalent vaccine that contains all three serotypes.

In September 2015 WHO declared that wild poliovirus type 2 has been eradicated from the planet – no cases caused by this serotype had been detected since November 1999. However, in 2015, there were 9 cases of poliomyelitis caused by the type 2 vaccine. For these reasons WHO decided to remove the type 2 Sabin strain from OPV, and switch from trivalent to bivalent vaccine in April 2016.

After OPV is ingested, the viruses replicate in the intestinal tract, providing immunity to subsequent infection. During replication in the intestine, the vaccine viruses lose the mutations that prevent them from causing paralysis. Everyone who receives OPV sheds these revertant viruses in the feces. In rare cases (about one in 1.5 million) the revertant viruses cause poliomyelitis in the vaccine recipient (these cases are called VAPP for vaccine-associated paralytic poliomyelitis). Vaccine-derived polioviruses can also circulate in the human population, and in under-vaccinated populations, they can cause poliomyelitis.

There were 26 reported cases of poliomyelitis caused by the type 1 or type 2 vaccine viruses in 2015. Nine cases of type 2 vaccine-associated polio were detected in four countries: Pakistan, Guinea, Lao People’s Democratic Republic, and Myanmar. Removing the type 2 strain from OPV will eliminate vaccine-associated poliomyelitis in recipients caused by this serotype. When the US switched from OPV to the inactivated poliovaccine (IPV) in 2000, VAPP was eliminated.

The problem with the trivalent to bivalent switch is that vaccine-derived type 2 poliovirus is likely still circulating somewhere on Earth. The last two reported cases of type 2 vaccine-associated polio in 2015 were reported in Myanmar in October. The viruses isolated from these cases were genetically related to strains that had been circulating in the same village in April of the that year. In other words, type 2 vaccine-derived strains have been circulating for an extended period of time in Myanmar; they have been known to persist for years elsewhere. If these viruses continue to circulate past the time that immunization against type 2 virus stops, they could pose a threat to the growing numbers of infants and children who have not been immunized against this serotype.

Eventually as type 3, and then type 1 polioviruses are eradicated, it will also be necessary to stop immunizing with the respective Sabin vaccine strains. The switch from trivalent to bivalent vaccine in April 2016 is essentially an experiment to determine if it is possible to stop immunizing with OPV without placing newborns at risk from circulating vaccine-derived strains.

Over 18 years ago Alan Dove and I argued that the presence of circulating vaccine-derived polioviruses made stopping immunization with OPV a bad idea. We suggested instead a switch from OPV to IPV until circulating vaccine-derived viruses disappeared. At the time, WHO disagreeed, but now they recommend that all countries deliver at least one dose of IPV as part of their immunization program. Instead of simply removing the Sabin type 2 strain from the immunization programs of 155 countries, it should be replaced with the inactivated type 2 vaccine. This change would maintain immunity to this virus in children born after April 2016. Such a synchronized replacement is currently not in the WHO’s polio eradication plans. I hope that their strategy is the right one.

TWiV 370: Ten out of 15

On episode #370 of the science show This Week in Virology, the TWiVomics review ten captivating virology stories from 2015.

You can find TWiV #370 at

TWiV 369: Camel runny noses and other JNK

On the latest episode of the science show This Week in Virology, a swarm of virologists discusses testing of a MERS coronavirus vaccine for camels, and how a neuronal stress pathway reactivates herpes simplex virus.

You can find TWiV #369 at

TWiV 366: Doctorates down under

On episode #366 of the science show This Week in Virology, Vincent visits Melbourne, Australia, where he speaks with four PhD students about their research projects and what it’s like to get a doctorate down under.

You can find TWiV #366 at Or you can watch the video below.

TWiV 354: The cat in the HAART

On episode #354 of the science show This Week in Virology, the esteemed doctors of TWiV review a new giant virus recovered from the Siberian permafrost, why influenza virus gain of function experiments are valuable, and feline immunodeficiency virus.

You can find TWiV #354 at

TWiV 351: The dengue code

On episode #351 of the science show This Week in Virology, the Masters of the ScienTWIVic Universe discuss a novel poxvirus isolate from an immunosuppressed patient, H1N1 and the gain-of-function debate, and attenuation of dengue virus by recoding the genome.

You can find TWiV #351 at

TWiV 349: One ring to vaccinate them all

On episode #349 of the science show This Week in Virology, Vincent, Alan and Rich explain how to make a functional ribosome with tethered subunits, and review the results of a phase III VSV-vectored Ebolavirus vaccine trial in Guinea.

You can find TWiV #349 at

TWiV 348: Chicken shift

On episode #348 of the science show This Week in Virology, Vincent and Rich discuss fruit fly viruses, one year without polio in Nigeria, and a permissive Marek’s disease viral vaccine that allows transmission of virulent viruses.

You can find TWiV #348 at

Permissive vaccines and viral virulence

chicken farmA permissive vaccine prevents disease in the immunized host, but does not block virus infection. Would a permissive vaccine lead to the emergence of more virulent viruses?

This hypothesis is based on the notion that viruses which kill their hosts too quickly are not efficiently transmitted, and are therefore removed by selection. However a vaccine that prevents disease, but not viral replication in the host, would allow virulent viruses to be maintained in the host population. It has been suggested that in this scenario, viruses with increased virulence would be selected if such a property aids transmission between hosts.

On the surface this hypothesis seems reasonable, but in my opinion it is flawed. One problem is that increased transmission might not always be associated with increased virulence. The more serious flaw lies in making anthropomorphic assessments of what we think viruses require, such as concluding that increased viral transmission is a desired trait. Our assumptions fail to recognize the main goal of evolution: survival. Evolution does not move a virus along a trajectory aimed at perfection. Change comes about by eliminating those viruses that are not well adapted for the current conditions, not by building a virus that will fare better tomorrow. All the viruses on Earth today transmit well enough, or they would not be here; yet some kill their hosts clearly much faster than others. The fact is that humans have little understanding of what drives virus evolution in large populations. Our assumptions of what constitute the selective forces are usually tainted by anthropomorphism.

This long preamble is an introduction to a series of findings which are purported to support the idea that permissive vaccines (the authors call them ‘leaky’ and ‘imperfect’ vaccines but I dislike both names because they imply defects) can lead to the selection of more virulent viruses. The subject of the paper is Marek’s disease virus (MDV), a herpesvirus that infects chickens. MDV is shed from feather follicles of infected chickens and is spread to other birds when then inhale contaminated dust. Vaccines have been used to prevent MDV infection since the early 1970s. These vaccines prevent disease, but do not block viral replication, and vaccinated, infected birds can shed wild type virus. The virulence of MDV has been increasing since the 1950s, initially from a paralytic disease, to paralysis and death. The authors wonder if the use of permissive Marek’s vaccines has lead to the selection of more virulent viruses.

To address their hypothesis, the authors inoculate vaccinated or unvaccinated chickens with a series of MDV isolates that range from low to high virulence. Unvaccinated chickens inoculated with the most virulent MDV died within a week and shed little virus. In contrast, most vaccinated birds survived infection with virulent viruses, and shed virus for the length of the experiment, 56 days.

A transmission experiment was done to determine if shed virus could infect other birds. The authors infected vaccinated or unvaccinated birds and asked if sentinel, unvaccinated chickens became infected. Unvaccinated birds died within 10 days after infection with virulent MDV, and did not transmit infection. In contrast, vaccinated birds survived at least 30 days, and co-housed sentinel animals became infected and died.

The experiments are well done and the conclusions are clear: more virulent Marek’s disease viruses replicate longer in vaccinated than unvaccinated chickens, and can be readily transmitted to other chickens. But these results do not prove that more virulent MDV arose because of permissive vaccines. Nor do the results prove in general that leaky vaccines lead to selection of more virulent viruses. The results simply show that a vaccine that does not prevent replication will allow transmission of virulent viruses.

To prove that vaccinated chickens can allow the selection of more virulent viruses, vaccinated chickens could be infected with an avirulent virus, and the shed virus collected and used to infect additional, vaccinated birds. This process could be repeated to determine if more virulent viruses arise. While the results of this gain-of-function experiment would be informative, they would be done in a controlled laboratory setting which would not duplicate all the selective forces present on a poultry farm.

The authors note that most human vaccines do prevent replication of infecting virus. They do not mention the one important exception: the Salk poliovirus vaccines. People who are immunized with the Salk vaccine can be infected with poliovirus, which will then replicate in the intestines, be shed in the feces, and transmitted to others. This behavior has been well documented in human populations, yet the virulence of poliovirus has not increased for the 60 years during which the Salk vaccine has been used.

I do not feel that these experimental results have general implications for the use of any animal vaccine. It is unfortunate that the work has been covered in many news sources with the incorrect implication that vaccines may be responsible for the emergence of more virulent viruses.