The Impact of R&D Decisions on the Downstream Immunization System. Focus on the last mile access-to-medicines issues in low- and middle-income countries.

For many human infectious diseases, in particular for those caused by viruses for which no treatment is available, it is of utmost importance to have effective vaccines at hand. Prevention of suffering and death from infectious diseases by means of prophylactic vaccination is the most (cost-)effective public health intervention available today. However, for many pathogens no such vaccines exist. Many vaccines have features that impede their successful use in remote, tropical, developing areas; among others, these include: (i) too complex in terms of high manufacturing cost of goods and long lead times, (ii) the need for a strict cold-chain (storage and transport), (iii) the requirement for repeated dosing/boosting, (iv) the use of sharps for injection that cannot safely be disposed afterwards, etc. For example, despite the availability of a highly effective yellow fever virus (YFV) vaccine, ~30.000 people die annually from yellow fever because the vaccine does not reach them. Moreover, the underlying fundamental technology gap further hampers the development of urgently needed new vaccines. Novel platform technologies are key to close this gap, not the least to be prepared to recurring outbreaks of emerging infectious diseases, such as recently MERS (Middle East, 2012), Ebola (West Africa, 2014), Zika (South America, 2015) and currently COVID-19. To combat this challenge, the Virology lab (Vaccine R&D, KU Leuven, Rega Institute for Medical Research, Lab of Prof. J. Neyts, co-promotor Dr. Kai Dallmeier) and the Research Center of the Access-To-Medicines (ATM - KU Leuven, Prof. N. Vandaele, promoter) have joined forces. Within this transdisciplinary research project we will combine the unique and very complementary expertise of both KU Leuven teams to link the vaccine development in the R&D phase to this ‘last mile’, i.e. to reach those people in need of vaccination, thereby realizing the immunization goal. Such a study will allow to obtain deep insights in the impact of decisions made in the R&D stage of novel technologies, such as the revolutionary novel vaccine platform technology called PLLAV (Plasmid-Launched Live-Attenuated Viral vaccine platform, patent WO2014174078, entirely owned by KU Leuven), on the entire immunization system. To achieve the immunization goals, a complex system of interrelated and interacting subsystems needs to be in place. Therefore, research by the ATM group will focus on modeling the immunization system, whereby a definite inter- and cross-disciplinary, human-centered approach is mandatory. We will showcase this novel concept of the immunization system for yellow fever and rabies vaccination in Kenya, representative for low and middle income (Sub Saharan) African health systems. The ultimate objective of this highly transdisciplinary project (biomedical research to engineer the vaccine on one hand and operations research/modeling/systems thinking on the other hand) is hence to set a solid and scientifically founded decision framework for the development of vaccines against neglected tropical diseases that match true public health needs and is feasible to implement in the future health system setting. In other words, we aim at the last mile and the system impact from the early R&D steps onwards.