Maximising the impact of inactivated polio vaccines
Authors: Elizabeth B Brickley, Peter F Wright
Journal: The Lancet Infectious Diseases (2017)

With the globally coordinated switch from the trivalent oral polio vaccine (OPV) to the bivalent OPV in April, 2016, the international public health community entered a new chapter in the endgame of polio. Although OPV has served as the cornerstone of polio eradication efforts over the past 30 years, trivalent inactivated polio vaccine (IPV) has re-ascended to prominence in the past year, now acting as the sole source of protective immunity against type 2 poliovirus in routine immunisation programmes. Despite its immense public health value, the global supply of IPV is failing to meet demand. The October, 2016, meeting of the Strategic Advisory Group of Experts on Immunization cautioned that, "the IPV supply situation is further deteriorating; 50 countries are experiencing delays in supply or stock-outs, a situation which is likely to persist until 2018".1WHOWeekly epidemiological record, 2 December 2016. World Health Organization, Geneva2016: 561-584Google Scholar Given the existing resource constraints, pragmatic solutions are urgently needed to maximise the impact of IPVs during the transitional and post-OPV immunisation era. In The Lancet Infectious Diseases, Birgit Thierry-Carstensen and colleagues2Rivera L Pedersen RS Peña L et al.Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial.Lancet Infect Dis. 2017; (published online April 25)http://dx.doi.org/10.1016/S1473-3099(17)30177-9PubMed Google Scholar report one such novel strategy in the form of reduced-dose IPVs administered intramuscularly with an aluminium hydroxide (Al) adjuvant. The three IPV-Al candidates were formulated at one-third, one-fifth, and one-tenth the concentration of standard IPV and administered to healthy children living in the Dominican Republic at 6, 10, and 14 weeks of age. The results of the well conducted phase 2 trial indicate that the antigen-sparing IPV-Als were able to achieve substantial (ie, ≥75%) seroconversion against the three serotypes of polio after only two vaccine doses. Promisingly, after three doses, all three formulations of IPV-Als achieved more than 94% seroconversion to poliovirus types 1, 2, and 3, and the seroresponses were non-inferior to those of the standard IPV, which was administered unadjuvanted, but at up to ten-fold higher concentrations. Enhancing the immunogenicity of IPVs is an important achievement in view of the ongoing shortfalls in IPV production by global pharmaceutical firms. Moving forward, an antigen-sparing IPV with adjuvant would be a welcome addition to the expanding portfolio of alternative IPV approaches under development, which also includes fractional (ie, reduced-volume) intradermal IPVs3Resik S Tejeda A Lago PM et al.Randomized controlled clinical trial of fractional doses of inactivated poliovirus vaccine administered intradermally by needle-free device in Cuba.J Infect Dis. 2010; 201: 1344-1352Crossref PubMed Scopus (106) Google Scholar, 4Mohammed AJ AlAwaidy S Bawikar S et al.Fractional doses of inactivated poliovirus vaccine in Oman.N Engl J Med. 2010; 362: 2351-2359Crossref PubMed Scopus (125) Google Scholar and enhanced potency high dose IPVs5Saez-Llorens X Clemens R Leroux-Roels G et al.Immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine in infants: a comparative, observer-blind, randomised, controlled trial.Lancet Infect Dis. 2016; 16: 321-330Summary Full Text Full Text PDF PubMed Scopus (34) Google Scholar that might limit the number of serial doses required to uniformly induce immunity. Overall, dose-sparing IPV strategies have the potential to reduce costs of immunisation activities,6Hickling J Jones R Nundi N Improving the affordability of inactivated poliovirus vaccines (IPV) for use in low- and middle-income countries: an economic analysis of strategies to reduce the cost of routine IPV immunization. Program for Appropriate Technology in Health (PATH), Seattle, WA2010Google Scholar facilitate the protection of individuals during outbreaks by enabling both prompt responses and high levels of coverage,7Bahl S Verma H Bhatnagar P et al.Fractional-dose inactivated poliovirus vaccine immunization campaign—Telangana State, India, June 2016.MMWR Morb Mortal Wkly Rep. 2016; 65: 859-863Crossref PubMed Scopus (26) Google Scholar and stretch dwindling vaccine supplies. However, selecting and then operationally optimising an IPV strategy for a specific context will be challenged by a number of logistical barriers (eg, scalability and costs of vaccine production and storage, availability of trained vaccinators, procurement of immunisation devices) and immunological considerations (eg, scheduling to mitigate interference by maternal antibodies, inducing seroprotection of an appropriate magnitude and duration).8Estivariz CF Pallansch MA Anand A et al.Poliovirus vaccination options for achieving eradication and securing the endgame.Curr Opin Virol. 2013; 3: 309-315Crossref PubMed Scopus (47) Google Scholar In preparing the global public health system to withstand shortages in IPV supply moving forward, it is also important to give due consideration to a limitation of all IPVs—namely, that inactivated vaccines appear to have a limited capacity to induce intestinal immunity against polio. There is no question that serum antibodies produced in response to IPVs are able to successfully protect vaccinees against paralytic polio by inhibiting viraemia and entry into the CNS. Perhaps less appreciated is that with polio—and probably many other pathogens replicating at mucosal surfaces—a vaccine's ability to induce mucosal immunity is tightly linked to the vaccine's capacity to block viral shedding and, thereby, potential onward transmission. Mounting evidence from OPV challenge trials5Saez-Llorens X Clemens R Leroux-Roels G et al.Immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine in infants: a comparative, observer-blind, randomised, controlled trial.Lancet Infect Dis. 2016; 16: 321-330Summary Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 9O'Ryan M Bandyopadhyay AS Villena R et al.Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.Lancet Infect Dis. 2015; 15: 1273-1282Summary Full Text Full Text PDF PubMed Scopus (58) Google Scholar, 10Hird TR Grassly NC Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.PLoS Pathog. 2012; 8: e1002599Crossref PubMed Scopus (147) Google Scholar indicates that, when delivered in a primary vaccine series, IPV seems to have only limited effects on the duration and degree of viral shedding. By contrast, the intestinal immunity induced by live, oral vaccines is close to achieving the ideal of sterilising immunity.10Hird TR Grassly NC Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.PLoS Pathog. 2012; 8: e1002599Crossref PubMed Scopus (147) Google Scholar, 11Asturias EJ Bandyopadhyay AS Self S et al.Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial.Lancet. 2016; 388: 158-169Summary Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 12Wright PF Connor RI Wieland-Alter WF et al.Vaccine-induced mucosal immunity to poliovirus: analysis of cohorts from an open-label, randomised controlled trial in Latin American infants.Lancet Infect Dis. 2016; 16: 1377-1384Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar Ultimately, blocking transmission (eg, via integrated OPV-IPV intestinal immune-boosting strategies13John J Giri S Karthikeyan AS et al.Effect of a single inactivated poliovirus vaccine dose on intestinal immunity against poliovirus in children previously given oral vaccine: an open-label, randomised controlled trial.Lancet. 2014; 384: 1505-1512Summary Full Text Full Text PDF PubMed Scopus (82) Google Scholar, 14Jafari H Deshpande JM Sutter RW et al.Polio eradication. Efficacy of inactivated poliovirus vaccine in India.Science. 2014; 345: 922-925Crossref PubMed Scopus (88) Google Scholar and the development of the more highly attenuated and genetically stable novel OPVs) and thus reducing IPV demand for outbreak control is also a paramount consideration for capitalising on the utility of IPVs under the reality of existing supply limitations. Eradication of polio is tantalisingly close. In the final steps toward eradication and for the post-eradication era, there is a need for as many arrows in the quiver as possible, and it would be valuable to add aluminium hydroxide-enhanced IPV to that arsenal. We declare no competing interests. Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trialThe lowest dose (1/10 IPV-Al) of the vaccine performed well both after two and three doses. Based on these results, this new vaccine is under investigation in phase 3 trials. Full-Text PDF Open Access