Breakthroughs Blog: Vaccines

In this guest post Tom Harmon, senior policy analyst at the International AIDS Vaccine Initiative (IAVI), highlights a new analysis exploring the critical role of a vaccine in ending AIDS. Photo credit: IAVI When we talk about ending AIDS, what do we mean? The last dozen years have brought tremendous strides in reducing new HIV infections in low- and middle-income countries (LMICs), expanding lifesaving treatment to almost 16 million people living with HIV, and implementing programs to address the epidemic in populations at especially high risk, including women and girls. But we must continue to push for progress in treatment and prevention. The 2 million new infections in 2014 remain far too high, and almost 60 percent of people needing treatment are not getting it. So, when we talk about conclusively and durably ending AIDS and ensuring that it does not bounce back, our experience with other infectious diseases shows that a preventive vaccine will be necessary. The global effort to develop an AIDS vaccine has also recently experienced significant successes and steps forward. For example, we’ve never before seen such a diversity of approaches and partners, with follow-on trials based on the first candidate to show modest efficacy slated to begin later this year in South Africa, exciting new insights toward generating protective antibodies against HIV, and promising approaches toward inducing cellular immune responses that could control HIV infection. Still, there are more far-reaching questions we’re asked today by policymakers, advocates, communities, and even researchers themselves: What would the global response look like if an AIDS vaccine was available? How effective would it need to be? Would it be cost-effective and affordable? A new article, published in PLoS ONE aims to answer some of these crucial questions. The result of a collaboration between IAVI, Avenir Health, and AVAC that builds on work by UNAIDS, this model specifically explores a vaccine’s potential value in terms of preventing HIV infections in LMICs. We analyzed a vaccine’s potential impact depending on how well the world can achieve ambitious HIV and AIDS program objectives, how effectively it can prevent HIV infection, and how it can add to a response that also includes pre-exposure prophylaxis and treatment as prevention. We also looked at cost scenarios to see how a vaccine would stand up to cost-effectiveness criteria used by the World Health Organization to guide the introduction of new health technologies. Despite the potential for today’s tools to have a substantial impact on the epidemic, our results show that a vaccine is a critical piece to ending AIDS. Under our base scenario, a vaccine of 70 percent efficacy with strong uptake would reduce HIV infections in LMICs by 44 percent in its first 10 years and by 65 percent in 25 years, ultimately averting tens of millions of infections and saving millions of lives. Reduction of new annual HIV infections with PrEP, TasP and vaccination added individually and in combination to the Full Scale-up of IFE between 2015 and 2070. A vaccine would be impactful and cost-effective even at lower efficacy levels and costs far higher than many of today’s vaccines. Increasing a vaccine’s efficacy, ensuring it protects for a longer period of time, reducing the number of doses, lowering the cost of a dose, and more effectively rolling it out are all factors that would increase a vaccine’s impact and its value. Such a vaccine could cut the number of people needing treatment in half by the year 2070, and eventually reduce the total cost of fighting AIDS in LMICs even when the additional cost of implementing the vaccination program is included. While these data provide a powerful illustration of a vaccine’s potential value, we acknowledge and welcome discussions of its intrinsic limitations, which reflect the areas the AIDS vaccine field and future program implementers will need to tackle as we research, develop, and ultimately deliver a vaccine to the people who need it most. Such an analysis helps explore the parameters that determine the medical and economic impact and value of a future AIDS vaccine as part of the comprehensive HIV and AIDS response. This data can be a useful guide for research portfolio decisions as new candidates move closer to efficacy trials. In many ways these projections are as much a vaccine development and delivery “to-do list” as they are a crystal ball for what the future holds. A few weeks ago, the US Centers for Disease Control and Prevention organized a Grand Rounds presentation on how models are used to guide pandemic responses. This interesting panel was closed by Dr. Richard Hatchett, chief medical officer and deputy director for strategic sciences at the US Biomedical Advanced Research and Development Authority, who cited modeler Steven Bankes’ use of campfires as an analogy for predictive models, in that their value goes beyond their primary deliverable (be it light, heat, or data), as they just as importantly provide a “gathering place” for discussion between stakeholders. Our new model can perform just such a dual function, adding valuable context for a vaccine’s future role in ending the AIDS epidemic which has ravaged so many communities, while stimulating conversations and new questions on what we need to do in the real world to turn theory to impact.

Euvichol® produced by EuBiologics. Photo: IVI In January, GHTC member International Vaccine Institute (IVI) announced that a new oral cholera vaccine it developed in partnership with Korean biotech company EuBiologics, Co. Ltd.—Euvichol®—received prequalification from the World Health Organization (WHO), paving the way for the vaccine to be purchased by global procurement bodies like Gavi, the Vaccine Alliance and UNICEF. GHTC’s Breakthrough blog is joined by Jerome Kim, IVI’s Director General, to learn more about this exciting development which will ease global supply limitations of the oral cholera vaccine and expand affordable access in countries where the disease is endemic. Tell us why this breakthrough is so critical. Cholera is a potentially fatal diarrheal diseases that affects between 1.4 million and 4.3 million people each year and causes as many as 142,000 deaths annually in low-income countries. Cholera is endemic in more than 50 countries, with outbreaks often occurring during humanitarian or natural disasters. Oral vaccines against cholera have existed since the 1990s as a potential tool to stem outbreaks. However, because the disease primarily affects poor communities there wasn’t a stable market to create demand for vaccine production at an affordable cost for these countries. To create a stable market for the vaccine, WHO created an oral cholera vaccine stockpile in 2013 to make the vaccine available at an affordable price for vaccinations in epidemic situations and endemic countries. In recent years, increasing demand for the vaccine created supply pressures on the stockpile and limited more extensive implementation of the vaccine. The prequalification of Euvichol® by WHO means a third oral cholera vaccine producer has entered the market. This will significantly increase the number of oral cholera vaccines doses available worldwide and address global shortages. Euvichol® is also expected to help bring down costs and expand access. How did the vaccine come to be developed and prequalified? The prequalification of Euvichol® is the culmination of a five-year long partnership between IVI and Eubiologics, a Korean biotech company. IVI worked with partners in Vietnam, Sweden, India, and the United States to develop a reformulated oral cholera vaccine to meet the needs of low-income countries. IVI originally transferred the technology to an Indian biotechnology company Shantha Biotechnics. Shantha licensed the vaccine in India under the name Shanchol™ in 2009 and received WHO prequalification for the product in 2011. To strengthen the cholera vaccine market further, in 2010, IVI transferred the technology for the vaccine to Eubiologics, as a second producer and manufacturer. Eubiologics advanced the product through clinical trials, receiving licensure from the Korean Ministry of Food and Safety in January 2015. This paved the way for the product to receive WHO prequalification in December, 2015. The development of Euvichol® was supported by the Bill & Melinda Gates Foundation, the Republic of Korea, and Sweden. The Global Health Investment Fund (an impact investment fund sponsored by the Gates Foundation and other partners), Korea-Seoul Life Science Fund, Korea Investment Global Frontier Fund, and Green Cross Corporation also provided funding to Eubiologics. The creation of Euvichol® is a great example of how the contributions of public, nonprofit, and commercial partners can be leveraged to advance technology development for diseases impacting the poor. What’s next for the vaccine? EuBiologics has initiated production of 6 million doses of the vaccine for 2016, which is expected to double WHO’s stockpile. IVI will continue to work with the WHO and partners to promote uptake of the vaccine and make sure it is available and used in places where it is needed most.

Photo: National Institute of Allergy and Infectious Diseases (NIAID) Gavi, the Vaccine Alliance, signed an advanced purchase commitment, pledging to spend US$5 million on an Ebola vaccine currently under development by pharmaceutical company Merck & Co. The vaccine candidate was tested on 4,000 people in Guinea last year, and the results were promising: despite all participants having close contact with at least one Ebola patient, none developed the disease more than ten days after vaccination (several days are required for a vaccine to confer protection). The vaccine candidate—VSV-EBOV—was developed and tested in partnership with the Canadian and US governments, however, without the urgency of an outbreak, public-sector support moving forward is limited. The agreement guarantees that there will be a market for the vaccine, assuring Merck & Co. that they can recover investments in advanced development and manufacturing. This move will also enable Gavi to establish a stockpile of the vaccine so that it can be rapidly deployed in future outbreaks. New research suggests that 2.6 million stillbirths occur each year, 420,000 of which are attributable to malaria or syphilis infections. These results underscore the need for testing and treatment of malaria and syphilis in pregnant women, particularly in endemic regions. Fortunately, there are low-cost interventions that could drastically reduce adverse pregnancy outcomes attributable to malaria and syphilis infections. The malaria parasite is able to reside in the placenta, even when undetectable in the mother’s blood, and thus, preventative treatment for malaria is critical. The antimalarial sulphadoxine-pyrimethamine, which costs a mere $0.20 per patient, is recommended for use in pregnant women in endemic areas. In east and southern Africa, an estimated 5 percent of pregnant women are infected with syphilis and in Tanzania, up to half of stillbirths are caused by syphilis. However, one dose of penicillin can cure both maternal and congenital syphilis and prevent stillbirth—at just $1.40 per person. While malaria- and syphilis-related stillbirths can be prevented with the scale-up of existing medicines, many more could be prevented with interventions that are not appropriate for low-resource settings, which is particularly concerning as 98 percent of stillbirths occur in low- and middle-income countries. Further, the cause of stillbirth is often unknown, according to the Global Alliance to Prevent Prematurity and Stillbirth, and additional research is needed to determine and address these causes. There is little incentive for pharmaceutical companies to invest in antimicrobial research and development (R&D): antibiotics are prescribed for short periods of time and competition among antibiotics keeps prices low. However, with the spread of drug resistance, the “[financial] value assigned to antibiotics and diagnostics often does not reflect the benefits they bring to society,” according to a declaration authored by 80 pharmaceutical and diagnostic companies and released at this year‘s World Economic Forum in Davos, Switzerland. The declaration calls on governments to work with the pharmaceutical industry to spur antimicrobial R&D, identifying innovative financing mechanisms, including prizes (a Market Entry Rewards initiative) and intellectual property–related incentives. In response, the companies pledge to invest in R&D for new antibiotics, as well as improved diagnostics to prevent the unnecessary use of antibiotics (i.e., for viral conditions).

Last week, an oral cholera vaccine receivedWorld Health Organization (WHO) prequalification, a process of regulatory review which paves the way for procurement by United Nations agencies and international organizations. Up to 4.3 million cases and 142,000 deaths from cholera are reported annually, primarily in low- and middle-income countries, and the vaccine—Euvichol®—is 65 percent effective against the bacteria. Euvichol® was developed by GHTC member the International Vaccine Institute (IVI), and has been licensed to the Korean company Eubiologics, which plans to produce 6 million doses in 2016. The vaccine is a reformulated version of Shanchol™, which is licensed to Shantha Biotechnics in India, and was prequalified in 2011. According to the WHO, prequalification of Euvichol® could double the global supply of cholera vaccines. Euvichol® produced by EuBiologics. Photo: IVI Scientists have identified three compounds that could serve as the basis for a vaccine against onchocerciasis (river blindness). More than 17 million people globally are affected by river blindness, 70 percent of whom experience skin conditions, including itching and lesions, and 10 percent of whom develop eye conditions, leading to visual impairment. Without a vaccine, river blindness control programs use the antiparasitic drug ivermectin to treat the disease, however, ivermectin is not recommended for use in children under five. Additionally, in Central and Western Africa, where coinfection with Loa loa worms is common, use of ivermectin can lead to fatal brain inflammation. The team hopes to initiate safety and efficacy trials for a potential vaccine candidate by 2020 and 2025, respectively. The Global Fund to Fight AIDS, Tuberculosis and Malaria is launching an “e-marketplace” through which global health product procurers (i.e., governments and nongovernmental organizations) can purchase everything from drugs and diagnostics to condoms and cars. The e-marketplace will be an online platform utilizing the Global Fund’s pooled procurement mechanisms. Through this mechanism, the Global Fund negotiates with manufacturers and purchases large quantities of global health commodities; governments and other organizations are then able to purchase products directly from the Global Fund, reducing product and transaction costs. This approach also improves demand forecasting and ensures a sustainable supply of products. The launch of the e-marketplace will be phased: while in the first quarter of 2016, only bednets will be available, artemisinin combination malaria medicines, malaria and HIV and AIDS diagnostics, and antiretrovirals will be available by the end of the year. The e-marketplace will initially be limited to Global Fund grant recipients, and 10 to 20 countries are expected to utilize the platform in 2016. The Global Fund hopes to open the e-marketplace to more buyers in the future and eventually offer products that are not part of Global Fund agreements, enabling procurers to independently compare quotes from different manufacturers.