Polio vaccination: preparing for a change of routine

Edward P. K. Parker and Nicholas C. Grassly

Department of Infectious Disease Epidemiology, St Mary’s Campus, Imperial College London, London, UK

The Global Polio Eradication Initiative is on the brink of a major milestone. As of April 2016, the type 2 component of oral poliovirus vaccine (OPV) will be removed from all immunisation activities globally. This transition, which is the first step in the synchronised withdrawal of all OPV serotypes, is essential to the polio endgame: although wild type 2 polioviruses have not caused a case of paralytic disease since 1999, vaccine viruses of this serotype have continued to cause rare cases of vaccine-associated paralytic poliomyelitis among OPV recipients or their close contacts,1 as well as sporadic emergences of circulating vaccine-derived polioviruses (cVDPVs), wherein Sabin strains mutate to regain neurovirulence.2

Preparations for the withdrawal of type 2 vaccine viruses have seen significant shifts in routine immunisation practices across much of the globe. To provide type 2 immunity by alternative means, more than 90 countrieshave introduced at least one dose of inactivated poliovirus vaccine (IPV) into their routine immunisationprogrammes since 2013.3 These efforts have laid the foundation for the replacement of trivalent OPV (tOPV) with a bivalent formulation targeting serotypes 1 and 3 (bOPV) in all routine and supplementary immunisation activities, after which type 2 OPV will be used only in a monovalent form if required in an outbreak response.

Although essential to the polio endgame, these programmatic shifts lead us into uncharted terrain. How will the transition to a mixed schedule of bOPV and IPV impact humoral immunity to the three poliovirus serotypes? And how will these changes impact intestinal immunity, which is required to halt the spread of viruses from person to person?

The report in The Lancet by Asturias and colleagues is part of a series of recent trials specifically tasked with answering these questions.4 In a randomised, controlled study across sites in Colombia, Guatemala, Panama, and the Dominican Republic, infants received three doses of bOPV according to the Expanded Programme on Immunization schedule (6, 10, and 14 weeks of age) alongside one dose of IPV at 14 weeks, or two doses of IPV at 14 and 36 weeks. Control groups received three doses of bOPV or tOPV. Serum antibodies against all three poliovirus serotypes were assessed at multiple timepoints, while intestinal immunity to serotype 2 was examined by administering a challenge dose of monovalent type 2 OPV (mOPV2).

A robust humoral immune response to serotypes 1 and 3 was seen in all study arms (with seroconversion rates exceeding 97%), confirming that bOPV is highly immunogenic when administered either with or without IPV.5-7 For serotype 2, seroconversion was observed in approximately 10% of infants after three doses of bOPV, probably reflecting community exposure to type 2 viruses shed by recipients of tOPV. Notably, the addition of a single dose of IPV at 14 weeks of age elicited type 2 seroconversion in 80% of infants –a result comparable to recent observations from Chile and India.6,7 These findings are reassuring given that many OPV-using countries have introduced just one dose of IPV into their routine schedules.

As expected, a high proportion of infants (>75%) who had received three doses of bOPV shed type 2 poliovirus 1 week after mOPV2 challenge. The addition of either one or two doses of IPV did not decrease this proportion. However, a modest decrease in the overall quantity and duration of shedding was seen among recipients of one dose of IPV, and this effect was amplified by a second IPV dose. While these findings confirm that IPV elicits a degree of intestinal protection,8,9 given the potential of wild polioviruses to circulate in populations immunised with IPV alone (as seen recently in Israel),10 it is unlikely that this protection would be sufficient to curb the spread of a type 2 cVDPV (cVDPV2),particularly in settings where poor sanitation and hygiene facilitate faecal–oral transmission.

Several gaps in our understanding of poliovirus immunity remain. Among infants in this study who had not seroconverted to serotype 2 before receiving mOPV2, seroconversion 1 week after challenge was seen in 115/162 (76%) who had received bOPV alone and 20/38 (53%) who had received bOPV alongside one dose of IPV. These infants were considered to have been ‘primed’–an interpretation shared by other recent trials that have observed a similar phenomenon.6,7 However, we remain uncertain as to the cause of this priming through homotypic or heterotypic mechanisms, and whether these individuals are protected from paralytic disease. Moreover, given that serum neutralising antibodies may begin to appear within 7 days following primary exposure to OPV,11 this definition of priming is up for debate.

We are entering a phase of significant transition in polio immunisation. Even with the encouraging response to serotype 2 reported in this study after one dose of IPV, poor routine immunisation coverage in high-risk areas and the risks of cVDPV2 emergences after tOPV withdrawal mean that type 2 poliovirus remains a threat to the polio endgame. High-quality surveillance for cases of poliomyelitis alongside enhanced monitoring of wastewater and sewage will be key to identifying the persistence of type 2 vaccine viruses after tOPV has been withdrawn. We must also be ready to respond rapidly with mOPV2 should an outbreak occur.

Declaration of interests

We declare no competing interests. NCG is a member of the WHO Strategic Advisory Group of Experts polio working group.

References

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3.WHO. Countries using and planning to introduce IPV and the global status of bOPV registration. 2016. (accessed March 10, 2016).

4.Asturias EJ, Bandyopadhyay AS, Self S, et al. Humoral and intestinal immunity induced by new schedules of bivalent OPV and one or two doses of IPV in an open, randomised, controlled trial in Latin America infants. Lancet 2016; in press.

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