The Poliovirus Endgame: Create ways to Accelerate, Sustain and Monitor Eradication (Round 6)
Although delayed, the progress made by the Global Poliovirus Eradication Initiative in reducing the incidence of disease caused by poliovirus has been extraordinary. This has been primarily due to the widespread use of the easily-administered oral poliovirus vaccines (OPV).
The effort to complete eradication, however, has met with a number of challenges for which solutions are not readily available. In particular:
- OPV and other orally administered enteric vaccines have shown reduced efficacy in children living in certain resource-poor environments.
- The interactions between OPV, live attenuated rotavirus vaccines, and other enteric vaccines are unclear. In particular, the existence, extent and potential mechanisms of vaccine interference are poorly characterized; and whether protection from diarrheal disease by rotavirus vaccine can enhance OPV efficacy is uncertain.
- Paralytic poliomyelitis incidence currently serves as a surrogate measure for the circulation of wild poliovirus in a region. However, as eradication nears the signal provided by paralytic disease will be eventually lost; new methods to monitor poliovirus circulation are increasingly necessary.
- Improvements in water and sanitation infrastructure are considered to be effective interventions for reducing poliovirus transmission; however, the true impact and relative importance of these measures in limiting transmission remain unclear.
Once eradication of wild polioviruses has been achieved, a number of challenges will remain:\
PV can, in rare instances, cause vaccine-associated paralytic poliomyelitis. Furthermore, OPV is excreted in the stool and, though initially attenuated, can regain characteristics of wildtype neurovirulence and/or transmission—resulting in circulation of vaccine-derived poliovirus (VDPV) and outbreaks of poliomyelitis.
Thus, post-eradication, OPV use must cease. However, risks of re-introduction of polioviruses into the population will remain. These risks include persistent shedding of viruses by immunodeficient individuals; escape of OPV or wild virus from containment facilities, laboratories, or manufacturing sites; and bioterrorism. Further, current plans for control of a wild or vaccine virus outbreak in the post-eradication period call for use of OPV, running the risk of generating new VDPV outbreaks
- Therefore, routine use of the inactivated poliovirus vaccine (IPV) is being considered as a means of ensuring any re-introduced viruses do not spread. However, administration of the current IPV is accompanied by a number of challenges, as follows.
- Manufacturing of IPV currently requires wild virus, thus introducing the possibility for escape of wild virus from manufacturing facilities.
- The delivery and administration of the current IPV requires more infrastructure than that of OPV (e.g., trained medical staff, needles, medical waste, etc.), and will thus be far more expensive and difficult to deploy using current approaches.
- Currently, per dose, IPV is more expensive than OPV (due to both the cost of manufacturing and the scale of production).
- Unlike OPV, the current IPV does not induce strong mucosal immunity in the intestinal tract; thus, IPV less-effectively prevents viral shedding. Post-eradication, re-introduction of wild poliovirus might result in widespread transmission through an IPV-vaccinated population due to intestinal infection and shedding.
What We Are Looking For:
The goal of this topic is to solicit innovative approaches to address the roadblocks listed above. We seek proposals that may be "off the beaten track" and daring in premise, and are clearly differentiated from approaches currently being developed or employed. Proposals must (i) have a testable hypothesis, (ii)include an associated plan for how the idea would be tested or validated, and;(iii) yield interpretable and unambiguous data in Phase I if they are to be considered for Phase II funding.
Specific examples to be considered include:
- New approaches, which are practical, scalable and affordable, for improving the immunogenicity and effectiveness of poliovirus vaccines in children living in resource-poor regions where oral vaccine efficacy is reduced;
- Rigorous short-term studies to directly test the ability of practical and low-cost water and/or sanitation interventions to reduce the transmission of poliovirus in populations where the force of infection is high;
- Novel and sensitive tools, which do not rely on sentinel cases of paralytic poliomyelitis, to detect wild polioviruses, poliovirus vaccine strains and VDPVs, and to discriminate among these;
- Novel, non-invasive methods to measure poliovirus vaccine-induced mucosal immune responses (humoral and/or cellular) that correlate with reduction in virus shedding;
- Studies aimed at determining direct and indirect functional interactions among rotavirus, poliovirus, and other enteric vaccines;
- Novel approaches to formulate and administer IPV that do not require trained medical personnel or hypodermic needles for administration, provide substantial dose sparing, and lower the overall cost without compromising efficacy;
- Novel ways to substantially increase the level of intestinal mucosal immunity induced by IPV in order to prevent viral shedding;
- Novel methods to produce an equally or more efficacious inactivated or subunit poliovirus vaccine that do not require wild virus for production and can be manufactured at scale in a cost-effective manner;
- Original studies examining factors/processes involved in the waning of mucosal intestinal immunity and methods/interventions for counteracting these factors/processes.
We will not consider funding for:
- Modifications, similar to those already being undertaken, of Sabin vaccine strains for use in IPV production;
- Interventions focused solely on behavioral modifications;
- Antiviral discovery, development, or implementation;
- Surveys of sanitation conditions in resource-limited settings that are not directly linked to data that accurately report or test OPV efficacy;
- Surveillance or monitoring systems;
- Epidemiological or burden of disease studies;>
- Conventional, indirect measures of mucosal immunity (e.g., circulating IgA antibodies), invasive measures, or measures that do not provide a direct comparison to protection from shedding;
- Modified delivery methods for IPV that require skills greater than are currently required for administration of OPV in the field, represent incremental modifications of hypodermic administration, or do not have the potential for substantial dose sparing or production at scale;
- Incremental modifications of existing approaches;
- Studies without specific, testable hypotheses.
Grants will be selected on ability to create impact in the context of our existing global health priorities. For more information on The Bill & Melinda Gates Foundation's priority global health conditions, please click here.