Improving IPV

The Advisory Committee on Poliomyelitis Eradication (ACPE) recommended in 2004 that the eradication of wild polioviruses (WPVs) will be followed by the discontinuation of immunization by oral poliovirus vaccines (OPV) as soon as feasible, a goal endorsed by the World Health Assembly (WHA) in May 2008. However, before OPV can be stopped globally, the following six prerequisites were defined to minimize the risks of poliovirus re-introduction or re-emergence:

1. certify wild poliovirus eradication and containment of wild polioviruses
2. ensure a global surveillance and notification capacity
3. establish a global stockpile of monovalent OPVs and a mechanism to respond to emergent poliovirus
4. implement IPV requirements in countries that retain poliovirus in laboratories or production facilities and establish ‘affordable’ options for IPV use in any setting
5. synchronize cessation of OPV globally
6. appropriately contain Sabin polioviruses.

High IPV coverage will be a requirement for countries which maintain poliovirus stocks in the post-OPV era to reduce the consequences of an inadvertent release. However, other countries may also choose to maintain polio immunity, using IPV.

To put IPV within reach of any country which may choose to use it after OPV cessation, WHO is pursuing a range of approaches to establish ‘affordable’ strategies for IPV use (i.e., to achieve immunity at a cost similar to that achieved through OPV) following OPV cessation:

1. to establish affordable options for IPV use in any setting
2. to develop safer processes for IPV production.

To meet the first objective, the GPEI is pursuing a multi-pronged research agenda:

   a) dose-reduction strategy using intradermal administration of fractional IPV doses

   b) schedule requiring fewer doses (for example, two doses given six months apart)

   c) adjuvant use to reduce the quantity of antigen required in the vaccine

   d) safer IPV production processes to facilitate manufacture in low-cost sites

To meet the second objective, the GPEI is working with academia, government and industry to develop:

   a) Sabin-IPV

   b) “further-attenuated” Sabin seed strains for IPV production.

Currently, dose-reduction trials are nearing completion in Cuba and Oman. Both trials are testing intradermal injection at 1/5th of the standard intramuscular dose, but using different schedules.

Prior evidence suggests that fractional dose administration may produce similar serologic immunity to the standard intramuscular dose. In addition, since the dermis is a mucosal surface, the intradermal injection may actually stimulate IgA mucosal immunity, which may enable immunized children to prevent or shorten the period that poliovirus replicates in the intestinal tract.

Several groups of investigators are interested in testing different adjuvants for use with IPV. Furthermore, the GPEI has entered into a multi-agency collaboration to bring Sabin-IPV to the proof-of-principle stage. Clinical trials for Sabin-IPV are presently taking place in Japan and India, with the first regulatory approval for this product envisioned as early as 2009.