Methods 40 (2006) 77–85 www.elsevier.com/locate/ymeth 1046-2023/$ - see front matter  2006 Elsevier Inc. All rights reserved. doi:10.1016/j.ymeth.2006.05.021 Introduction to Part II Economic and practical challenges to the formulation of vaccines against endemic infectious diseases such as malaria Magdalena Plebanski a,¤ , Ester Lopez a , Owen Proudfoot a,1 , Brian M. Cooke b , Mark von Itzstein c , Ross L. Coppel b a Vaccine and Infectious Diseases Laboratory, Burnet Institute at Austin, Studley Road, Heidelberg, Vic. 3084, Australia b Department of Microbiology, Monash University, Vic. 3800, Australia c Institute for Glycomics, GriYth University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Qld. 9726, Australia Accepted 2 May 2006 Abstract Herein, we analyze in general the current vaccine market and identify potential factors driving and modulating supply and demand for vaccines. An emphasis is placed on changes in regulation in the last 20 years which have led to increased indirect costs of production, and which can create a barrier against the timely use of technological advances to reduce direct costs. Other deWning industry characteristics, such as Wrm numbers and sizes, cost and pricing strategies, nature extent and impact of Government involvement and international regu- lation are noted. These considerations, far from being removed from basic vaccine research, inXuence its ability to achieve aims that can be then progressed into eVective vaccine products. We discuss speciWcally the development of particulate vaccines against malaria, a major lethal disease and health problem prevalent in Africa, including some key economic and methodological challenges and opportuni- ties. We note some practical issues blocking the development of eVective particulate vaccines for the Third World, mainly driven by the regulatory spiral noted above.  2006 Elsevier Inc. All rights reserved. Keywords: Vaccine; Economic; Infectious diseases; Malaria 1. The vaccine market In the decade of 1967–1977, smallpox was eradicated after a massive worldwide vaccination campaign, using pri- marily cowpox products similar to the one discovered by Edward Jenner in the XVIII century [1]. Today billions of dollars each year are spent worldwide on preventive vacci- nation against a range of viral and bacterial diseases, and the vaccine market is predicted to continue proWtable growth [2–5]. The number of vaccines recommended by International and National health advisory organizations for childhood and adult vaccination in the First World has increased from a few to well over a dozen in the last 20 years. During this time there has also been a 4- to 100-fold increase in the real price of vaccines [2–5]. Threat of product-liability lawsuits in the 1970 and 1980s, saw the number of vaccine companies shrink from about a dozen companies to four. The threat of costly liti- gation of this type will discourage smaller companies from entering or remaining in vaccine production. Further it is really only the large pharmaceutical companies, with a vari- ety of drug and vaccine products to oV-set temporary cash Xow limitations and a highly proWtable business model that may be able to provision adequately for such potential risks. To encourage companies to enter and/or remain in vaccine production, the US government enacted legislation to establish a liability fund in 1986 to compensate patients who suVered injury as a result of vaccination. The Bill and Melinda Gates Foundation have also taken steps to * Corresponding author. Fax: +61 3 9287 0643. E-mail address: mplebans@burnet.edu.au (M. Plebanski). 1 Present address: Bio-organic and Medicinal Chemistry Laboratory, Burnet Institute at Austin, Studley Road Heidelberg, Vic. 3084, Australia.