Allen Ross: Vaccination alone will not halt the next global pandemic

A combination of strategies are required to save lives

A US$1-billion initiative was launched earlier this year with the aim of having vaccines ready in order to prevent the next global pandemic. The Coalition for Epidemic Preparedness Innovations (CEPI) was launched at the World Economic Forum in Davos, Switzerland, with US$460 million in backing from Norway, Germany, Japan, the Wellcome Trust and the Bill & Melinda Gates Foundation.1-3 The organization expects to raise the full US$1 billion that it needs for the next 5 years by the end of this year.1-3 Moreover, CEPI has selected 3 pathogens on which to focus their initial vaccination efforts.1-3 However, the vaccines for these pathogens are in the very early stages of development (preclinical stage) and may take decades before they are ready for use in an epidemic.2 Despite Bill Gates’ claim that DNA/RNA vaccines (third-generation vaccines) can serve as a “vaccine pipeline” to accelerate vaccine development against other pathogens, there is no licensed DNA or RNA vaccine approved by the US Food and Drug Administration for human use.4 There is no Th1-adjuvant in existence which may prove to be a vital component of a future viral vaccine. Furthermore, a vaccine, once developed, cannot be tested in a Phase II or III clinical trial as there are few or no cases outside an epidemic for most of the potential pathogens. I believe CEPI’s focus solely on vaccination is a mistake. CEPI needs to carefully consider other innovations (passive immune therapy, antiviral drug discovery, adjuvant discovery, high-throughput viral genome sequencing) and capacity building initiatives (diagnostics, real-time reporting, zoonotic surveillance in animal reservoirs, mathematical modelling, GIS risk mapping) that will compliment vaccination.

Potential pathogens

Emerging infectious diseases are primarily zoonotic and viral (HIV, SARS, Ebola, MERS-CoV, Lassa Fever, Nipah virus), originating in wildlife populations from the tropics.5 WHO recently deemed 11 pathogens as the most likely to cause severe outbreaks but the rationale for this list is unclear. CEPI has chosen only 3 pathogens (Nipah virus, Lassa fever and MERS-CoV) to commence vaccination efforts but again what is the rationale for their selection? Nipah virus is a zoonotic disease with high fatality rates. Human-to-human transmission is common in Bangladesh and novel paramyxoviruses continue to emerge.6 Lassa fever is a viral haemorrhagic illness responsible for disease outbreaks in West Africa.7 It is a zoonosis with its reservoir host (the mouse Mastomys natalenis) distributed across sub-Sahara Africa.7 MERS-CoV is another zoonotic disease with pandemic potential. Like Lassa fever and Nipah virus, there is no specific drug treatment and vaccine development is still at the stage of animal experimentation.8 In recent years multiple zoonotic influenza A strains have emerged in humans (H5N1, H5N6, H7N9, H10N8) that have pandemic potential, but the current quadrivalent influenza vaccine (A-H1N1, A-H3N2, B- Phuket/3073/2013, B- Brisbane/60/2008) does not cover their serotypes.9 The U.S. Centres for Disease Control and Prevention (CDC) ranks H7N9 as the flu strain with the greatest potential to cause a global pandemic. Given the severe illness and fatalities associated with these influenza A strains clearly they should be a CEPI priority.

Building capacity

Vaccines for candidate pathogens may be decades away and new pathogens may arise from the tropics for which there is no vaccine. The recently developed Ebola vaccine (rVSV-ZEBOV) was built on the back of 40 years of research and the durability of the vaccine is questionable.10 No licensed vaccine is 100% efficacious or effective. We therefore, must have other strategies in place if a vaccine is not available. This would include building national capacities of low and middle-income countries. According to a recent report by the United Nations International Labour Organization almost half of the world’s population does not have access to healthcare.11 In Africa the number of rural people who don’t have access to healthcare is 83%.11 Most of the existing rural healthcare centres in Sub-Saharan Africa currently lack access to clean water, electricity, medical equipment, essential medicines, IT, and trained staff. During a pandemic it is these rural healthcare centres that will serve as the first line of defense.

At the World Economic Forum this year (2017) President Alpha Condé of Guinea made a passionate plea for help for improvements in national healthcare systems, community health services, and technology transfer in Africa. But to date this has largely been ignored. The World Bank’s new Pandemic Emergency Financing Facility does not cover pandemic preparedness or national reconstruction efforts. CEPI has put all its eggs in the vaccine basket, but vaccines may not pan out and vaccine-based solutions also ignore the underlying problem of building national capacities and surveillance in the developing world. Real solutions will come from a broader focus as advocated by Alma-Ata declaration of 1978.12, 13

Allen Ross is a professor and chair of Tropical Medicine & Infectious Diseases with Griffith University, Australia, and a Physician Scientist with Menzies Health Institute Queensland. His expertise and research interests lie in the realm of global health, medical microbiology, tropical infectious diseases, disease control, pandemic planning, and vaccination.

I thank the National Health and Medical Research Council, Australia, for providing financial support for my research.

Competing interests: I have read and understood the BMJ policy on declaration of interests and have no relevant interests to declare.

Provenance and peer review: Not commissioned; externally peer reviewed.

References:

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  2. Butler D. Billion-dollar project aims to prep vaccines before epidemics hit. Nature. 2017 Jan 18;541(7638):444-445. doi: 10.1038/nature.2017.21329.
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  • Mrs. Cedroni

    Oh just pick one already, Bill! ☠

  • Richard Hatchett

    We welcome the opportunity to set out the vital role we believe CEPI will play in epidemic and pandemic preparedness(1) and to respond to some of the issues raised by Professor Allen Ross.

    We agree with his contention that vaccines are not a panacea and that multiple strategies are needed to address the increasing risk of epidemic disease – ranging from investments in public health infrastructure to innovations in diagnostics and treatments.

    Acknowledging these points does not undermine the argument that the world needs a better system to produce proven vaccines against known epidemic threats. This was the conclusion of four expert reports on the Ebola outbreak.

    Had an Ebola vaccine existed in 2014, thousands of lives might have been saved(2). The world now has a vaccine that has demonstrated 100% effectiveness, thanks to the extraordinary efforts of an ad-hoc global coalition, which developed and tested an Ebola vaccine at unprecedented speed. CEPI seeks to establish a more sustainable model for epidemic vaccine development so that next time, the world is ready to act.

    Prof Ross questions the three pathogens chosen by CEPI as initial priorities. As a new organisation with a fundraising target of $1bn, we believe we must focus to have the most impact.

    CEPI took as its starting point the WHO’s R&D Blueprint for Action to Prevent Epidemics(3). This contains a list of priority pathogens likely to cause severe outbreaks in the near future, and for which few or no medical countermeasures exist.

    CEPI’s Scientific Advisory Committee(4) chose MERS-CoV, Lassa fever and Nipah virus based on a set of criteria including the risk of an outbreak occurring, transmissibility of the pathogen, burden of disease, feasibility of vaccine development and the current pipeline candidates.

    Prof Ross raises an important point about the risks to global health of influenza A strains. However, CEPI’s rationale is to develop vaccines for which market incentives and other sources of support for advanced research and development are lacking. We do not believe this to be the case here.

    Thanks to the far-sighted commitments of CEPI’s initial investors, we are moving at pace to deliver on the first phase of our mission. But we need to do more: with more funding, we could move faster and potentially expand the list of pathogens we address. We call on other governments to support this crucial endeavour to create new vaccines for a safer world.

    Dr Richard Hatchett, Chief Executive, CEPI

    1. Brende B, Farrar J, Gashumba D, Moedas C, Mundel T, Shiozaki Y, Vardhan H, Wanka J, Røttingen JA. CEPI-a new global R&D organisation for epidemic preparedness and response. Lancet. 2017 Jan 21;389(10066):233-235. doi: 10.1016/S0140-6736(17)30131-9.

    2. Merler S, Ajelli M, Fumanelli L, Parlamento S, Pastore Y Piontti A, Dean NE, Putoto G, Carraro D, Longini IM Jr, Halloran ME, Vespignani A. Containing Ebola at the Source with Ring Vaccination. PLoS Negl Trop Dis. 2016 Nov 2;10(11):e0005093. doi: 10.1371/journal.pntd.0005093.

    3. http://www.who.int/blueprint/en/ (accessed 14 June 2017)

    4. http://cepi.net/governance#Scientific-Advisory-Committee (accessed 14 June 2017)