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About poliovirus

Poliovirus is an enterovirus which is transmitted by the fecal-oral route. The virus is ingested, transits the stomach, and replicates in the lining of the gut where it causes a short-term diarrhea. The virus is shed in the feces for several weeks after resolution of symptoms. In about 1 in 200-1000 cases, the virus escapes the intestine, enters the bloodstream and infects the nervous system where it causes the classic paralytic symptoms associated with the disease.

Existing polio vaccines

There are two types of poliovirus vaccines in current use. One is the killed Salk vaccine, which consists of chemically inactivated wild poliovirus. As there are three serotypes of poliovirus, the Salk vaccine contains a representative amount of each serotype. The Salk vaccine is administered intramuscularly, and being a killed vaccine, predominantly induces systemic antibodies. These protect against disease by preventing spread from the gut to the nervous system. However, the Salk vaccine does not induce strong mucosal immunity, so poliovirus can replicate freely in the intestines of even vaccinated individuals, and the infection can then be spread to unvaccinated contacts.

The second vaccine is the Sabin vaccine, which is a live-attenuated vaccine. It contains weakened vaccine strains of each of the three serotypes. The Sabin vaccine is given orally, replicates in the intestines of vaccinees, induces both mucosal and systemic immunity, and protects against infection of the intestine by ingested virulent poliovirus. The Sabin vaccine also has drawbacks; notably, it can revert to a virulent form, and there are documented cases of circulating revertant Sabin poliovirus causing outbreaks of disease in areas from which the natural virus had been previously eradicated. The Sabin vaccine has been used to eradicate poliovirus from most of the globe. However, there remain pockets of endemic disease in some of the poorest parts of the world. In these areas of Africa and the Indian subcontinent, children who have received multiple vaccinations with the Sabin vaccine still develop incomplete immunity to poliovirus and can suffer from paralysis. In these places, intestinal parasites and other infections are probably activating the innate immune system which interferes with the replication of the Sabin vaccine strains in the gut, thus preventing the development of immunity to poliovirus.

How GVI technology can make a difference

Switching to the Salk vaccine may help solve this problem, but carries at least three liabilities. First, it is expensive to manufacture. Second, manufacture can only be done under high containment for fear of release of the virulent virus prior to chemical inactivation. And third, lack of protection in the gut would mean failure to interdict circulation of natural poliovirus. The GVI adjuvant has the potential to greatly improve vaccination with the Salk vaccine so that less of this expensive vaccine would be required and so that it would be capable of inducing mucosal immunity for protection of the gut. Because the Salk vaccine plus adjuvant would be delivered intramuscularly, immunization would not be prevented by an activated environment in the gut. Thus, we hope that the GVI adjuvant could finally enable the worldwide eradication of poliovirus.

Program achievements and outlook

Collaborating with the Netherlands Vaccine Institute (NVI/RIVM), we have tested their cGMP manufactured Salk vaccine in conjunction with the GVI adjuvant. In mice, the adjuvant improved the level of systemic antibodies by a factor of 4-8 for each of the three serotypes in the Salk vaccine. While the Salk vaccine alone did not induce cellular immunity, immune cells were induced in the presence of the adjuvant. Finally, intestinal IgA and IgG, indicative of mucosal immunity, were induced with the adjuvant, whereas these were not detected in mice receiving Salk alone. Scientists at NVI/RIVM have conducted a rat potency test with the Salk vaccine and the Salk vaccine plus adjuvant. This test is the international standard for determining the potency of each batch of Salk vaccine. With the adjuvant, comparable levels of potency were achieved with 1/7 the amount of vaccine. This dose sparing effect was highly significant. An even more impressive dose sparing effect was found in this test with inactivated Sabin vaccine.

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