Circulating Vaccine-Derived Poliovirus and the Eradication Endgame
A recent paper published in Journal of Virology describes sporadic and sustained outbreaks of illness from vaccine-derived polioviruses in Nigeria.[i] This study draws attention to what is often called the polio endgame – the vaccines and immunization activities that will be necessary to eradicate polio, given the ability of vaccine-derived viruses from the live poliovirus vaccine to circulate and cause disease.
To understand the complications of eradicating polio, it’s necessary to know that three types of wild poliovirus have been identified. Types 1 and 3 are responsible for all cases of wild polio in the remaining polio-endemic countries of Pakistan and Nigeria. (Very recent cases of polio in Kenya and Somalia are due to Type 1 wild poliovirus.)[ii] Type 2 wild poliovirus has not been detected since 1999, when it was found in Uttar Pradesh, India. It is presumed to be eliminated.[iii]
What has led to the seeming eradication of wild Type 2 poliovirus and not to the eradication of the other types? Several factors may have contributed. Type 2 poliovirus in the Sabin oral polio vaccine (OPV, or tOPV for the trivalent formulation) is the most highly immunogenic of the types in the vaccine and provides superior type-specific immunity than vaccine Types 1 and 3. (In fact, it may even dampen the effects of Types 1 and 3 vaccine viruses.) Additionally, Type 2 vaccine virus is especially effective at spreading to secondary contacts and immunizing them.[iv] So, the vaccine’s effectiveness for Type 2 is amplified in communities, and this may have hastened its disappearance.
The milestone of eliminating wild Type 2 poliovirus, however, has been overshadowed by the fact that vaccine-derived Type 2 polioviruses (VDPV2) are emerging and causing vaccine-acquired paralytic poliomyelitis (VAPP) in some areas. This has been particularly common in Nigeria, but has also occurred in Madagascar, Afghanistan, Ethiopia, India, Democratic Republic of Congo, Somalia, and Yemen. (All cases involved VDPV2; Mozambique had an emergence of a Type 1 VDPV.) The map below from the CDC shows vaccine-derived poliovirus detection until June 2012.
Surveillance in Nigeria has recorded about 23 emergences of VDPV2, one of which led to that virus circulating for about six years. The authors of the Journal of Virology paper calculated that in Nigeria, about 700,000 infections have resulted from cVDPV2 since 2005. (Only a small percentage of polio infections result in paralytic disease, so many fewer cases of VAPP have been noted.)
The Nigerian VDPV2s have resulted in most cases as the vaccine viruses recombined with other enteroviruses.[v] The VDPV2s regained virulence, thereby causing infection and disease in some cases and circulating when shed by those infected. Because trivalent OPV immunization coverage rates were low in some parts of Nigeria, and as immunization programs focused on using monovalent OPV1 and OPV3 to target wild virus outbreaks, a larger number of individuals were vulnerable to Type 2 poliovirus and provided a pool of susceptibles.
It is clear that another eradication challenge is nested within the larger challenge of polio eradication: we must eradicate VDPV2. To address the problem of VDPV2 while wild Types 1 and 3 are still circulating, WHO now recommends eliminating trivalent OPV and adding a dose of trivalent inactivated poliovirus vaccine (TIPV) before the first doses of a bivalent Types 1 and 3 OPV (bOPV). TIPV should prevent infection with any circulating VDPV2s, and they should gradually disappear.[vi]
As a recent WHO report says, the benefits of an IPV/bOPV schedule are many:
[f]ollowing OPV2 withdrawal, IPV vaccination will help to (i) prevent poliomyelitis in IPV-vaccinated individuals exposed to vaccine-derived poliovirus type-2 (VDPV2) or wild poliovirus type-2 (WPV2), (ii) improve the response to monovalent OPV type-1 (mOPV1) or an additional dose of IPV in a type 2 polio outbreak, (iii) reduce the transmission of a reintroduced type 2 poliovirus, and (iv) accelerate wild poliovirus eradication by boosting immunity to wild poliovirus types 1 and 3.[vii]
However, there are also challenges with using IPV, particularly in developing countries. IPV is administered as a shot, which is more complicated to give than the oral vaccine. Production capacity for IPV is limited as well, and vaccine manufacturers in emerging markets may need to begin producing the vaccine to ensure its global availability.
When Types 1 and 3 polioviruses are finally eliminated in the wild, then the oral vaccines will need to be suspended and IPV used until OPV-vaccinees no longer excrete VDPVs. The need for IPV will grow, as countries transition from using a single dose of IPV prior to bOPV to the full three-dose IPV series. Production of IPV, however, will be complicated by the fact that WHO guidelines call for higher levels of biological security when working with the virulent IPV strains after elimination of the wild viruses. Fewer facilities will be equipped to work under the more stringent guidelines.
Meanwhile, researchers are investigating alternatives to the now 60-year old IPV. The Bill & Melinda Gates Foundation is supporting research into several different vaccine strategies: vaccines using empty poliovirus capsids and virus-like particles, recombinant vaccines, and alternate vaccine delivery techniques.[viii] Another strategy might be to use Sabin virus strains in a new formulation of IPV; because they are less transmissible and less virulent, the Sabin strains will be less expensive to produce in IPV.[ix]
Monitoring and detecting wild and vaccine-derived polioviruses and disease will be crucial to the success of endgame strategies. We'll continue to read the weekly reports from the Global Polio Eradication Initiative to get the latest updates on the shifting target of polio eradication.
Burns et al. Multiple independent emergences of Type 2 vaccine-derived polioviruses during a large outbreak in northern Nigeria. Journal of Virology. May 2013 vol. 87 no. 9 4907-4922. http://jvi.asm.org/content/early/2013/02/06/JVI.02954-12.abstract
Caceres VM, Sutter, RW. Sabin monovalent oral polio vaccines: Review of past experiences and their potential use after polio eradication. Clinical Infectious Diseases. 2001;33:531-41.
Centers for Disease Control and Prevention. MMWR. Update on vaccine-derived polioviruses — worldwide, April 2011–June 2012 September 21, 2012 / 61(37);741-746 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6137a3.htm
MacNeil, DG. Polio reappears in the horn of Africa. New York Times. 5/27/2013 http://www.nytimes.com/2013/05/28/health/polio-reappears-in-the-horn-of-africa.html
Sutter RW, Kew, OM, Cochi, I. Poliovirus vaccine-live. In: Plotkin S, Orenstein W, Offit PA. Vaccines, 5th edition, Philadelphia: Saunders, 2008.
WHO. Bulletin of the World Health Organization. Ending polio, one type at a time. Volume 90, Number 7, July 2012, 477-556. http://www.who.int/bulletin/volumes/90/7/12-020712/en/
WHO. Weekly epidemiological record. 1/4/2013. No. 1, 2013, 88 , 1–16. http://www.who.int/wer/2013/wer8801.pdf
[i] Burns et al. Multiple independent emergences of Type 2 vaccine-derived polioviruses during a large outbreak in northern Nigeria. Journal of Virology. May 2013 vol. 87 no. 9 4907-4922
[ii] Global Polio Eradication Initiative. Horn of Africa polio outbreak. 5/23/2013. http://www.polioeradication.org/tabid/488/iid/300/Default.aspx
[iii] Centers for Disease Control and Prevention. MMWR. Update on vaccine-derived polioviruses — worldwide, April 2011–June 2012 September 21, 2012 / 61(37);741-746 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6137a3.htm
[iv]Sutter RW, Kew, OM, Cochi, I. Poliovirus vaccine-live. In: Plotkin S, Orenstein W, Offit PA. Vaccines, 5th edition, Philadelphia: Saunders, 2008.
[v] Burns, et al.
[vi] Bulletin of the World Health Organization. Ending polio, one type at a time. Volume 90, Number 7, July 2012, 477-556. http://www.who.int/bulletin/volumes/90/7/12-020712/en/
[viii] Grand Challenges in Global Health. Poliovirus eradication grants, May 2013. http://www.grandchallenges.org/Explorations/Pages/GrantsAwarded.aspx?Topic=Poliovirus%20eradication&Round=all&Phase=all
[ix] Caceres VM, Sutter, RW. Sabin monovalent oral polio vaccines: Review of past experiences and their potential use after polio eradication. Clinical Infectious Diseases. 2001;33:531-41.