From trivalent to bivalent oral poliovirus vaccine

Antibodies bound to poliovirusFor the first time since April of 1955, recipients of poliovirus vaccine will no longer receive all three serotypes. This past Sunday the World Health Organization orchestrated a synchronized switch from trivalent to bivalent oral poliovirus vaccine (OPV) in 150 countries.

The reason for the switch is clear: type 2 poliovirus was declared eradicated last year, and the only remaining cases are cause by vaccine-derived type 2 polioviruses. After oral administration of poliovirus vaccine, the virus replicates in the intestine, conferring immunity to subsequent infection. In all recipients of the vaccine the viruses lose the mutations that make them safe for humans. Consequently a small number of recipients, and their contacts, contract poliomyelitis from the vaccine.

To prevent further cases of poliomyelitis caused by circulating vaccine-derived polioviruses, WHO planned a synchronized, global switch from trivalent OPV to bivalent OPV on 17 April 2016. By July of 2016 all remaining stocks of the Sabin type 2 poliovirus strains, which are used to produce OPV, will also be destroyed.

My concern with this strategy is that type 2 vaccine-derived polioviruses continue to circulate. Whether they will continue to do so long enough to cause an outbreak of paralytic disease in the cohort of new infants that do not receive type 2 vaccine is a mattern of conjecture. In case there is an outbreak, monovalent type 2 oral poliovirus vaccine is being stockpiled by WHO. Of course, re-introduction of this vaccine will be accompanied by more circulating vaccine-derived poliovirus in the environment, and vaccine-associated disease, the very event WHO is trying to end with the trivalent to bivalent switch.

Type 3 poliovirus has not been isolated since 2012. Only type 1 poliovirus still causes outbreaks in two countries: Pakistan and Afghanistan. The inability to vaccinate in those countries, due to conflict, is delaying eradication. The recent killing of seven police officers who were protecting polio vaccinators by the Pakistani Taliban is an example of this difficulty.

Developing a great vaccine is not the only requirement for preventing infectious disease: you also have to be able to deploy it.

Image: Antibodies bound to poliovirus by Jason Roberts.

Is bivalent poliovirus vaccine a good idea?

polio-immunizationA new bivalent poliovirus vaccine, consisting of infectious, attenuated type 1 and type 3 strains, has been deployed in Afghanistan. The use of this vaccine was recommended by the Advisory Committee on Poliomyelitis Eradication, the global technical advisory body of the Global Polio Eradication Initiative. Considering the polio experience in Nigeria, the elimination of type 2 poliovirus from the vaccine might have serious consequences.

There are three serotypes of poliovirus, all of which can cause poliomyelitis. Infection with one serotype of the virus does not confer protection against the other two; therefore poliovirus vaccines have always included all three serotypes (they are trivalent). The attenuated vaccine that is used in the eradication effort is an infectious vaccine. The vaccine is ingested, the viruses replicate in the intestine, and immunity develops. Viruses of all three serotypes undergo genetic changes during replication in the alimentary tract. As a consequence, the vaccine recipient excretes polioviruses that can cause paralysis. These so-called vaccine-derived polioviruses (VDPV) can cause outbreaks of poliomyelitis in non-immune people, as described in Polio among the Amish.

Poliovirus type 2 was declared eradicated from the globe by the World Health Organization in 1999. When type 2 poliovirus was eliminated, many countries began using monovalent type 1 and type 3 vaccines: one vaccine for type 1 and another for type 3. As a consequence of this immunization strategy, population immunity to type 2 poliovirus declined. Not unexpectedly, there was an outbreak of type 2 poliovirus in Nigeria in 2006. The surprise was that the outbreak was caused by a poliovirus type 2 vaccine strain.

Before 2003, the year that Nigeria began a boycott of polio immunization, the trivalent polio vaccine was used. Immunization resumed with monovalent types 1 and 3 vaccine in 2004. Therefore the source of the VDPV type 2 is most likely the trivalent vaccine used before 2003.

The press release at announcing the bivalent vaccine proclaims:

Of the three wild polioviruses (known as types 1, 2 and 3), type 2 has not been seen anywhere in the world since 1999.

The statement ignores the fact that there is vaccine-derived type 2 poliovirus in the world – and it can cause polio as well as ‘wild’ poliovirus. Such strains have been isolated in Nigeria as recently as October 2009. Why isn’t the type 2 vaccine being used in Afghanistan when it is very likely that vaccine-derived type 2 poliovirus is still circulating? Just because we haven’t isolated type 2 poliovirus recently doesn’t mean that it’s gone. No type 2 poliomyelitis was detected in 1999, yet the vaccine-derived virus was silently circulating in humans.

What will be the WHO response to an outbreak of type 2 polio in Afghanistan? They will probably deploy trivalent vaccine, as was done in Nigeria in 2006. But this approach will simply lead to another cycle of eradication and emergence of type 2 polio. It’s time to begin using inactivated poliovirus vaccine, which I’ve been dreaming about for some time.