With success still frastratingly elusive, the leaders of the global program to eradicate poliovirus are reintroducing an old tool to fight the disease: an oral polio vaccine designed specifically to protect against the most pervasive strain of poliovirus, known as type 1. The only vaccine used in the 16-year eradication campaign targets three strains of the virus. The new monovalent oral polio vaccine (mOPV) — a version of which was used extensively before the adoption of trivalent OPV in the 1960s — offers "more wallop per punch," says Brace Aylward, who coordinates the program from the World Health Organization (WHO).
It is not a silver bullet, caution officials at WHO and the U.S. Centers for Disease Control and Prevention. Program officials also stress that mOPV will augment, not replace, the well-honed strategy of immunizing every child under age 5 where polio remains a threat with several doses of trivalent OPV each year. But if mOPV works as hoped, "it may be what it takes to tip the scale," says David Heymann, who heads WHO's eradication effort.
The project, which began in November, is on an accelerated track. Sanofi Pasteur in Lyon, France, and Delhi-based Panacea Biotec have promised to deliver 200 million doses this spring. WHO officials say this could well be the fastest a vaccine has been produced and approved. The agency actually wanted the vaccine even sooner, says Francois Bompart, vice president of medical affairs for Sanofi, but the company simply could not retool production from trivalent OPV fast enough. Still, if the vaccine is ready by May, as planned, the partners should be able to deliver two rounds in Egypt and parts of India before the beginning of the high season in July to September, when viral transmission peaks. The mOPV plan, to be announced by the end of January, offers another key benefit: It will give officials a leg up on testing a key component of the vaccine stockpile needed to deal with emergency out-breaks once eradication is achieved.
The use of mOPV is designed to root out the virus in areas where it is most entrenched — typically, overcrowded slums with abysmal sanitation and booming birthrates, like greater Cairo and parts of western Uttar Pradesh, Bihar, and Mumbai in India. Despite dramatic increases in the number of national immunization days last year and the percentage of children reached in each one, viral transmission still persists in these areas, notes Hamid Jafari, who directs the global immunization division at CDC. Meanwhile, the epidemiology of the disease has shifted, says Roland Sutter of CDC. The program has successfully cleared the world of type 2 poliovirus, he says, and type 3 is "just hanging on by its teeth." In Mumbai and all of Egypt, for instance, type 3 has not been detected since October and December 2000. That opens the door for the reintroduction of mOPV against type 1 poliovirus.
Since the early 1970s, polio experts have known that trivalent OPV simply isn't as effective in hot tropical climes, requiring perhaps five to eight doses to confer immunity instead of the standard three (Science, 26 March 2004, p. 1960). In Egypt and parts of India, especially, conditions are "very, very ripe for the virus," says Jafari. Although Egypt recorded just one case of paralytic polio in 2004, environmental samples collected from open sewers show that the type 1 poliovirus is well established in the ecosystem. The same is true in parts of India; Mumbai, for instance, reported just one case of paralytic polio in 2004, but 84 environmental samples tested positive. "So the question is, do we keep pounding away, or do we get some sharper edge to our tool?" asks Jafari. He suspects that edge will come from a new version of mOPV.
Past experience with mOPV has demonstrated that it is much more potent in prompting an immune response. Data from five tropical countries showed that just one dose of mOPV type 1 conferred immunity in 81% of those vaccinated, says Sutter. By contrast, the seroconversion rate for one dose of trivalent OPV in tropical countries is roughly 30% to 40%. The benefit occurs because the live attenuated vaccine virus, which replicates in the gut, doesn't have to compete with the other two virus types for cells susceptible to infection.
MOPV also has a long safety record, notes Bompart. But because no company has produced it in years, and it is no longer licensed, the vaccine must be reviewed as a new product. Regulatory agencies in Egypt and India have agreed to expedite the review based on historical data, while also requiring new clinical trials and postmarketing studies.
Sanofi is manufacturing 50 million doses for Egypt, and Panacea is ready to produce up to 150 million for India for introduction in May. Although all children under age 5 in the target areas will receive mOPV, the partners expect the biggest payoff to come from vaccinating very young children with low or little immunity, who are most likely to transmit the disease: "We really do need to get the youngest ones immunized as quickly as possible," says Sutler. "MOPV will help us do it faster."
At this stage, cautions Aylward, the benefits are theoretical. And even if mOPV does boost immunity as expected, says Bompart, it is not clear that it will make a "real world" difference in terms of stopping transmission. One concern is that the promise of a more effective vaccine will divert attention from the need to reach every single child with multiple doses of trivalent OPV, which must continue, says Aylward.
Even so, the idea is gaining steam. Polio expert Paul Fine of the London School of Hygiene and Tropical Medicine says the plan makes "good sense" scientifically and also shows that the program has an "open-mindedness" toward new tactics and vaccines, which may be needed to finish the job.
PHOTO (COLOR): Ripe environment Poliovirus persists in the slums of India and Egypt.
PHOTO (COLOR)
By Leslie Roberts
