Next Generation Inactivated Poliovirus Vaccine: The Future Has Arrived

(See the Major Article by Sun et al on pages 1317–25.) The containment requirements restrict the production of Salk-IPV to current low force-of-polio-infection industrialized countries in Europe (Belgium, Denmark, France, and The Netherlands), and North America (Canada) [1]. As a safer-for-production alternative, and to facilitate production of inactivated poliovirus vaccine (IPV) in developing countries, the World Health Organization (WHO) promoted the development and technology transfer of IPV based on Sabin strains (Sabin-IPV) as early as 2005 [2]. The development of Sabin-IPV goes back more than 30 years, with the initial evaluation by Lederle Laboratories (currently part of Pfizer) in 1988 [3]. Subsequently, 2 manufacturers (the Japan Poliomyelitis Research Institute [JPRI] and the Institute of Medical Biology, Kunming, China) started in the mid-1990s with their own in-house development of Sabin-IPV. These efforts were rewarded with regulatory approval in 2012 in Japan for a combination diphtheria and tetanus toxoid and acellular pertussis (DTaP) vaccine with Sabin-IPV [4]. This vaccine is used exclusively in routine immunization program in Japan for poliomyelitis prevention. The report by Sun M et al. [5] published in this issue of the Clinical Infectious Diseases describes part of the scientific evaluation required for regulatory approval of Sabin-IPV in China. It provides detailed information on a dose-finding study for inactivated poliovirus vaccine based on Sabin strains (Sabin-IPV), compares the immunity achieved by Sabin-IPV with traditional Salk-IPV, and reports on the cross-neutralization achieved with 19 different poliovirus strains of all 3 serotypes (wild, vaccine-derived, and Sabin). Encouragingly, the dose-finding study (a phase II trial) evaluating 3 formulations demonstrated the viability and robustness of Sabin-IPV in achieving equal or higher immunogenicity (seroconversion and antibody titer) than the traditional Salk-IPV (produced by a WHO-prequalified IPV manufacturer]. Furthermore, cross-neutralization of 19 different strains revealed similar neutralization profiles by Sabin-IPV compared with Salk-IPV. A single virus, a vaccine-derived poliovirus type 2 from an individual with primary immunodeficiency (iVDPV2), was not neutralized by immune sera induced by Sabin-IPV nor Salk-IPV. The data generated by Sun M et al. [5] are of great interest to public health and will put to rest concerns about the scientific feasibility of Sabin-IPV [6, 7]. The results demonstrate clearly that the immunity profile of Sabin-IPV and Salk-IPV appear to be comparable. These data and a large phase III trial also led to the regulatory approval of Sabin-IPV by the Chinese authorities in 2015 [8]. The Sabin-IPV is now used in routine immunization programs in China in a WHO-recommended schedule of bivalent (types 1 + 3) oral poliovirus vaccine (bOPV) at 2, and 3 months, and simultaneous administration of bOPV and Sabin-IPV at 4 months. At least 3 other vaccine manufacturers in China are either in preclinical or clinical development of Sabin-IPV. In order to broaden the market participation for Sabin-IPV, and more recently, to generate alternatives (and competition) for the established IPV suppliers, WHO established in 2008, a technology transfer hub at Intravacc (the Institute for Translational Vaccinology) in the Netherlands [9]. The ensuing calls for expression of interest in 2010 and later resulted in 7 international (5 of these are continuing) and 1 national developing country manufacturers being selected for technology transfer. The manufacturers are located in India, China, and Korea. Similarly, the Research Foundation for Microbial Diseases of Osaka University (Biken, which includes JPRI) has established a Sabin-IPV technology transfer program with Indonesia and Vietnam. And finally, a number of vaccine producers are pursuing their own in-house development of Sabin-IPV. Thus, 3 manufacturers have licensed Sabin-IPV (Biken, Osaka, and Kakuketsan, Kumamoto, Japan; and Institute of Medical Biology, Kunming, China), and >10 manufacturers are in the development stage, some have or are starting the clinical development this year, but the earliest significant quantities of Sabin-IPV to the international market will not be available until 2019 or later. The current routine schedule for poliomyelitis prevention consists of 3 doses of bOPV and 1 dose of IPV. This IPV dose is intended to maintain an immunization base against type 2 poliovirus, and really a risk mitigation strategy should there be an emergence or importation of type 2 virus. This routine immunization recommendation is under discussion for the time after polio eradication has been achieved. At this point, it appears that a schedule that induces >90% seroconversion to all 3 serotypes is considered [10], requiring additional supplies of IPV. Thus, it appears that there is light at the end of the supply tunnel. The IPV vaccine supply deterioration affecting at least 50 countries (either with inability to introduce, or stock-outs because of inability to resupply) will eventually be resolved. Until then, the world will be on edge, hoping that the birth cohorts without type 2 immunity (born after the switch in April 2016) will not be exposed to poliovirus type 2. And if they do, the Global Polio Eradication Initiative has established a stockpile with monovalent type 2 oral poliovirus vaccine (mOPV2) that can be deployed rapidly after release by the Director General of WHO and should rapidly increase the population immunity against poliovirus type 2 and control endemic and epidemic transmission. Potential conflicts of interests. The authors have no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.