Cost of production of live attenuated dengue vaccines: A case study of the Institut Butantan, Sao Paulo, Brazil

International Vaccine Institute, Seoul, Republic of Korea.
Vaccine (Impact Factor: 3.62). 03/2012; 30(32):4892-6. DOI: 10.1016/j.vaccine.2012.02.064
Source: PubMed


A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed.

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Available from: Richard T Mahoney, Mar 06, 2014
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    • "The vaccination program included vaccine transport, storage and administration for a three dose scheme [7] [8] [23]. The price of each vaccine dose was approximated using per dose production costs and ranges estimated from a study which analyzed vaccine production costs of an attenuated chimeric tetravalent dengue vaccine produced at the Butantan Institute in Brazil [24]. Based on results from two dengue vaccine meta-analysis and two phase 3 efficacy trials, the vaccine side effects were not considered [7–9,25]. "
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    ABSTRACT: Background: Dengue is one of the most important vector-borne diseases worldwide, and annually, nearly 390 million people are infected and 500,000 patients are hospitalized for severe dengue. Argentina has great variability in the risk of dengue transmission due to eco-climatic reasons. Currently no vaccines are available for dengue even though several vaccines are under development. Objective: The aim of this study was to estimate the cost-effectiveness of a dengue vaccine in a country with heterogeneous risk of dengue transmission like Argentina. Methods: The analysis was carried out from a societal perspective using a Markov model that included both vaccine and disease parameters. Utility was measured as disability adjusted life years (DALYs) averted, and the incremental cost-effectiveness ratio (ICER) of the vaccination was expressed in 2014 American dollars (US$) per DALY averted. One-way and probabilistic sensitivity analyses were performed to evaluate uncertainty in model outcomes, and a threshold analysis was conducted to estimate the highest possible price of the vaccine. Results: The ICER of the vaccination program was found to be US$ 5714 per DALY averted. This value is lower than 3 times the per capita GDP of Argentina (US$ 38,619 in 2014); 54.9% of the simulations were below this value. If a vaccination program would be implemented the maximum vaccine price per dose has to be US$1.49 for a vaccination at national level or US$28.72 for a targeted vaccination in high transmission areas. Conclusions: These results demonstrate that vaccination against dengue would be cost-effective in Argentina, especially if carried out in predetermined regions at high risk of dengue transmission. However, these results should be interpreted with caution because the probabilistic sensitivity analysis showed that there was considerable uncertainty around the ICER value. The influence of variations in vaccine efficacy, cost and other important parameters are discussed in the text.
    Full-text · Article · Dec 2015 · Vaccine
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    • "We assume that Sanofi will act in a rational manner and agree to a price that allows all of its volume to be sold, since artificial restriction of supply below 100 million doses will not increase prices but will be associated with substantial negative community pressure. Production costing of the future Butanten-NIH-licensed vaccine plant has been based on a 60 million dose capacity (Mahoney et al., 2012). The planned capacity of other plants is not known. "
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    ABSTRACT: Drugs offer a complementary approach to vaccines for preventing the progression of symptoms and onset of the severe manifestations of dengue. Despite the rapid maturation of the research and development infrastructure for dengue drugs and the increasing frequency of dengue inhibitors reported in the scientific literature, the potential size of the market for dengue drugs has not been articulated. In the present work, extrapolating from publicly available information, we explored the economic burden attributable to dengue, the impact of dengue vaccines on clinical case loads, a possible alternative to tiered pricing for products for neglected diseases, and defined the maximum potential market for a dengue drug. Our projections suggest that in 2006, the annual global burden of dengue was US $1.7billion. Our proposed alternative to existing tiered pricing structures is that during a temporary period of market exclusivity, individual countries would pay 50% of the per-case equivalent of economic costs saved through the use of a dengue drug. This would yield prices per case of US $13-$239 depending on drug effectiveness and cost of medical and indirect costs and lost productivity in different countries. Assuming that such a pricing scheme was embraced, the maximum potential market for a dengue drug or drugs that on average reduced 40% of economic costs might be as high as US $338million annually. Our simulations suggest that dengue vaccines will begin to reduce the clinical case load of dengue in 2022, but that the number of cases will not decrease below 2006 levels and the proportion vaccinated will remain well below that required for the onset of herd immunity during the period of market exclusivity after the licensure of the first wave of dengue drugs.
    Full-text · Article · Sep 2012 · Antiviral research
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    ABSTRACT: Dramatic increases in dengue (DEN) incidence and disease severity have been reported, in great part due to the geographic expansion of Aedes aegypti and Aedes albopictus mosquitoes. One result is the expanded co-circulation of all dengue 1-4 serotype viruses (DENV) in urban areas worldwide, especially in South and South-East Asia, and South America. DEN disease severity ranges from asymptomatic infections to febrile dengue fevers (DF) to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). There is an urgent need for a safe and effective tetravalent DEN vaccine. Several live attenuated, tetravalent DEN vaccine candidates have been generated by recombinant DNA technology; these candidates are capable of providing immunity to all four DENV serotypes. In this paper we review (a) recombinant live-attenuated DEN vaccine candidates in terms of deletion, antigen chimerization, and the introduction of adaptive mutations; (b) strategies for improving tetravalent vaccine attenuation; and (c) live-attenuated DENV vaccine development.
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