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.

Trivalent influenza vaccine for the 2010-2011 season

influenza-vaccineThe World Health Organization and the US Food & Drug Administration have decided on the composition of the influenza virus vaccine that will be used during the 2010-2011 season in the northern hemisphere. The trivalent preparation will contain the following influenza virus strains: A/California/7/2009 (H1N1); A/Perth/16/2009 (H3N2); and B/Brisbane/60/2008. The same trivalent vaccine is also being used to prepare for the upcoming winter in the southern hemisphere.

The A/California/7/2009 (H1N1) virus is the pandemic strain that was used in the 2009 H1N1 monovalent vaccine. That virus has not yet undergone sufficient antigenic drift to warrant selection of a new strain for the vaccine. Note that a seasonal H1N1 strain from previous years will not be included in the vaccine. This change has been made because epidemiological evidence suggests that these viruses will probably not circulate at significant levels during the 2010-2011 northern hemisphere season. Although the vast majority of circulating influenza viruses in humans are related to the 2009 H1N1 pandemic strain, sporadic influenza A(H3N2) activity continues to be reported in several countries. This is the reason why an H3N2 component is part of the vaccine.

The selection of viruses for seasonal flu vaccines is based on which influenza viruses circulate during the previous season. Sample viruses are collected by 130 national influenza centers in 101 countries and data on disease trends are analyzed by the four World Health Organization (WHO) Collaborating Centers for Reference and Research on Influenza. Vaccine viruses are selected which will most likely protect against the main circulating viruses during the next influenza season. WHO makes recommendations about which specific virus strains should be included in the vaccine. Individual countries then decide which viruses will be included in the influenza vaccine.

Even though the 2009 H1N1 strain has not undergone significant antigenic changes, it’s important to be immunized again in anticipation of the next influenza season. That’s because immunity conferred by the vaccine isn’t particularly long lasting. As Adolfo Garcia-Sastre told me today*, even if influenza didn’t change, you would still have to be immunized every year to protect against infection.

*I recorded our conversation. Look for it at TWiV within the next few weeks.