High development costs and risk of failure, as well as once- or twice-in-a-lifetime use, are just some of the hurdles depressing incentives for drugmakers to develop vaccines.
That's why governments and nonprofit groups play such a large role in spurring development.
"Current markets and incentives do not effectively coordinate the efforts of vaccine developers in government, academic and industry, making it difficult to share knowledge and build upon successes to advance vaccine development," said Orin Levine, director of the vaccine delivery team at The Bill & Melinda Gates Foundation.
"The financial commitment required to license new vaccines is significant, and often the most lucrative drug markets are not the ones with the greatest public health need."
Here's a roundup of the major government incentives to spur vaccine R&D from the U.S. and Europe:
US vaccine incentives: Research and regulation
Funding from the National Institutes of Health and the Centers for Disease Control and Prevention support better understanding of the basic science for vulnerable populations such as newborns, infants and older people. Developing clinical trials for vaccines, particularly for those vulnerable groups, can be both an ethical and a scientific challenge. To this end, the Food and Drug Administration is implementing regulatory pathways that have greater flexibility, and supporting the use of biomarkers, statistical analysis and real-world evidence.
The 21st Century Cures Act also provides FDA funding for biomarker development and identification of protective vaccine antigens and potency, an agency spokesperson said in an email.
"To respond to the challenges in conducting clinical trials and the changing clinical research environment, it is recognized that novel approaches are needed to facilitate efficient clinical development, such as reducing the size and duration of trials while still assuring confidence in the results," the agency added.
The FDA has put a focus on several therapeutic areas. A Staphylococcous aureus team was formed in 2009 to understand the roadblocks inhibiting development and evaluation of effective vaccines directed against the infection. The group is working to develop improved animal models and biological assays to advance basic research and vaccine development. It also collaborates domestically and internationally with other government agencies and the public health community to combat influenza.
"FDA has been diligent and successful in facilitating the development and licensure of safe and effective preventive vaccines for infectious diseases," said the FDA spokesperson. "We approved Trumenba and Bexsero for the prevention of serogroup B meningococcal disease. Both vaccines were designated as Breakthrough Therapy and Priority review and were approved via the Accelerated Approval regulatory pathway."
An additional incentive in the U.S. is the expansion of the Vaccine Injury Compensation Program. Originally covering only routine vaccinations for children, the program has been expanded under the 21st Century Cures Act to cover pregnant women as well. The program provides liability protections for companies, and may encourage innovation.
European vaccine incentives: Funding and guidance
The European Medicines Agency doesn't have a specific mechanism to vaccine development, a spokesperson explained in an email, but it does have a number of tools that support development of innovative products, including vaccines.
One example is the EMA's so-called PRIME scheme, which promotes development of medicines targeting unmet medical needs, according to the spokesperson.
Several other EU projects include Horizon 2020 and the EU 7th Framework Programme, which aims to speed up the vaccine development for European and global health challenges. The Innovation Partnership for a Roadmap on Vaccines in Europe created a blueprint to look at technologies needed to boost vaccine research, focusing particularly on the aging population, as well as emerging threats from hospital infections and low levels of prevention awareness and readiness.
The InnovFin Infectious Diseases Finance Facility, provided by the European Investment Bank, makes available standard debt and equity-type financing for innovators working on a range of ways to combat infectious diseases. This includes vaccines, and funding is available from €7.5 million to €75 million (approximately $8.7 million to $87 million) to cover project costs.
The European Vaccine Initiative, backed by seven research institutes, funds studies that support the transition between early studies and late stage clinical trials, particularly for vaccines relevant to low income populations.
Designing clinical trials for vaccines is one of the key challenges in development. A draft guideline from the EMA, issued for public consultation in April 2018, looks at safety, immunogenicity and efficacy studies for new preventive infectious disease vaccines. It lays out the factors to be considered in planning clinical trials and interpreting their results, in order to help companies to improve study design and data submission.
The EMA also has a number of disease-specific guidelines designed to facilitate the development of vaccines. A guidance for the development of vaccines and medicines that prevent and treat respiratory syncytial virus (RSV) infection, for example, was out for consultation until April 2018.
Vaccine development for infectious diseases is becoming increasingly important as levels of antimicrobial-resistant bacteria climb, and as international travel makes it easier to spread disease across and between continents. Increased support for companies developing vaccines, through more flexible regulatory systems and better alignment between countries over study requirements could speed vaccines to the market for both developed and developing countries.
"Thanks to vaccines, we are saving millions of lives and billions of dollars each year. Yet, one in seven children worldwide are not yet getting the full benefits of vaccines. The world has a tremendous opportunity to build on progress from the last few decades," said Levine.