The cost and challenge of vaccine development for emerging and emergent infectious diseases.

Over the past two decades, new infectious threats have emerged almost yearly. Outbreaks of Ebola virus disease, severe acute respiratory syndrome, Middle East respiratory syndrome, and Zika virus disease were interspersed between epidemics of H5N1 and H7N9 avian, swine, and H1N1 influenza. While most developed countries focused on these, disease due to Lassa, Nipah, and Crimean-Congo haemorrhagic fever viruses continued unabated. Other emergent pathogens such as severe fever and thrombocytopenia syndrome virus, and Powassan virus remain restricted in scope. When, in 2014, Ebola was detected in the capital cities of Guinea, Liberia, and Sierra Leone, the potential for a global pandemic expanding from travellers from affected regions or repatriation of infected health-care workers became a real concern. Ebola recalled the 2002 severe acute respiratory syndrome outbreaks in Hong Kong and Toronto and raised alarm during the 2015 Middle East respiratory syndrome outbreak in South Korea. And Zika, previously considered as self-limited, was newly associated with Guillain–Barré syndrome and fetal abnormalities.

The Ebola, severe acute respiratory syndrome, Middle East respiratory syndrome, and Zika outbreaks each highlighted substantial and varied gaps in vaccine development. First, vaccine research was reactive. Even for Ebola, despite three decades of vaccine research, human trials were limited to two vaccine candidates in the early to mid-2000s.4, 5 Second, vaccine trials occurred during epidemics with an evolving epidemiology. And third, while funding materialised to combat each outbreak, interest and financial support waned as case prevalences fell and imminent danger receded. These issues highlighted the urgent need for a coordinated and consistent approach to vaccine development for emerging and emergent pathogens.

In this context, WHO identified the need for coordination of countermeasures and convened a consultation to develop a so-called blueprint for infectious diseases with epidemic potential. Although organisations such as the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Biomedical Advanced Research and Development Authority have provided substantial support for select projects and focus areas, their missions are broader than vaccine research. The Coalition of Epidemic Preparedness Innovations (CEPI) was conceived to address this shortcoming.

In this issue of The Lancet Global Health, Dimitrios Gouglas and colleagues present a cost analysis for vaccine development for epidemic infectious diseases. Such an analysis is crucial to serve as a guide to harmonise finite funds and monetary needs to achieve CEPI's goal of successful testing through phase 2a of at least one vaccine per targeted pathogen. Although not part of CEPI's mandate, the eventual objective is successful vaccine licensure.

For the 11 priority pathogens identified in the WHO blueprint, 224 candidate vaccines in preclinical and clinical development were identified. The probability of success for a vaccine to advance to successive stages was modelled from the literature, with a 40–50% chance of advancement from preclinical to clinical studies and a composite prevalence of success through phase 2 of 10–13%. Gouglas and colleagues' actual data show that only 10·7% of vaccines have advanced to phase 1 and 2·7% to phase 2. Although consistent, these figures are slightly lower than the 10% prevalence of drug candidate licensure estimated by DiMasi and colleagues.

Gouglas and colleagues' stochastic model was based on actual expenditures provided by vaccine developers for pipeline vaccines. As the authors note, the accuracy of self-reported cost figures are unknown; also the prevalence of reporting was not provided. For some disease programmes, cost data might be rudimentary because work is ongoing. The cost of development through phase 2a, not including the initial discovery, was calculated as US$31–68. Including the risk of candidate non-advancement, costs per successful candidate could range from $319 to 469 million, consistent with cost estimates through licensure of $2·5 billion per successful candidate. Using these cost estimates, the total portfolio cost to advance at least one candidate vaccine through to phase 2a for each of the 11 target pathogens was $3·5–5·2 billion; a point at which stockpiling could conceivably occur.

One can ask whether there is a way to reduce both time and cost through phase 2 and eventual licensure while increasing potential for success. CEPI's funding model of parallel development of multiple candidates and a focus on platforms with previous known success are key to limiting time and cost. Another area not considered here is the ability to do efficacy trials, which might not be feasible for uncommon or geographically dispersed diseases such as severe fever with thrombocytopenia syndrome virus, Powassan virus, severe acute respiratory syndrome, and Middle East respiratory syndrome, although a potential solution might be to consider group-specific approvals on the basis of success of a vaccine platform for related viruses. Finally, the CEPI model provides the impetus for early-phase vaccine development for diseases with unknown commercial return; solutions to encourage development through licensure are, however, still needed.