Untitled-1 IMAGE UNAVAILABLE FOR COPYRIGHT REASONS © 1996 Nature Publishing Group http://www.nature.com/naturebiotechnology• ANALYSIS BUSINESS & REGULATORY NEWS WHO and UNICEF find vaccines too costly Officials of the World Health Organization (WHO, Geneva) and the United Nations Children's Fund (UNICEF, New York) have pointedly criticized industry and the biomed- ical research community over vaccine research and pricing policies in a recent comprehensive report on worldwide immunization efforts. Indeed, the report cites the approval of geneti- cally engineered hepatitis B vaccine in 1986 as signaling "that the days of cheap vaccines were over:' But both industry representatives and the two global health-care organizations agree that disease prevention programs need to take steps to harness the productive power of com- mercial biomedicine. "We need more dia- logue with industry;' says WHO Director General, Hiroshi Nakajima. The WHO-UNICEF report, "State of the World's Vaccines and Immunization;' lauds recent successful campaigns to deliver vac- cines against diseases-including polio, measles, neonatal tetanus, diphtheria, per- tussis, tuberculosis, hepatitis B, and yellow fever-to the world's children, particularly in developing countries. But the report also warns that, "unless the international com- munity continues to back scientific research and global immunization with adequate resources for new vaccines. . .the great promise of molecular biology and genetic engineering may be squandered:' High on the list of global vaccination campaigns are efforts to eradicate polio-a goal that officials expect to meet by the year 2000. In 1995, for instance, nearly half of all children under five, some 300 million, received supplementary doses of polio vac- cines during special national immunization days. But even here, officials are concerned over budget "shortfalls;' mainly from decreased donor funding, that now have the managers of this campaign scrambling for the $600-800 million needed for vaccine purchases, personnel, training, research, logistics, establishment of a cold chain to preserve vaccine activity, and development of a global laboratory network. The current full allotment of six childhood vaccines (against polio, diphtheria, pertussis, tetanus, measles, and tuberculosis) now costs less than $1 for the vaccines-plus $14 for program costs. The hepatitis B vaccine has been a touch- stone for the vaccine cost discussion. Nakaji- ma points out that the cost of the recombinant hepatitis B vaccine has been dropping, in part because several countries in the developing world, including China, Korea, and Cuba, now are manufacturing the prod- uct and making it widely available. However, he adds, unless its price falls below $1 per dose, this vaccine remains out of reach for much of the world. "We're not saying all vac- 1532 cines should be free;' says Carol Bellamy, executive director of UNICEF. "We're hoping for a healthy, competitive market and to cre- ate a varied pricing structure." But Thomas Bombelles, who specializes in international issues for the Pharmaceutical Research and Manufacturers of America Association (PhRMA, Washington, DC), argues that innovation can be expensive. "The development costs for vaccines are not all that much lower than for drugs;' he says. "R&D for vaccines is often on the lower end of the range for pharmaceutical products, but it can Child receiving an oral polio vaccine in a hospital in Phnom Penh, Cambodia. be from $50-350 million, which is still an awful lot of money, and there has to be a rea- sonable return on such development costs:' In any case, he says, "The cost is actually very small:' Even though its price is higher than that of older vaccine products, its effectiveness makes it a "fantastic bargain" when health outcomes are considered, he says. Other improved recombinant vaccine products are nearing regulatory review. For instance, Chiron Corporation (Emeryville, CA) announced in October that it is seeking regulatory clearance for the marketing of Pertugen, a diphtheria, tetanus, and geneti- cally engineered acellular pertussis (DTaP) vaccine for infants and children. Pertugen is the first recombinant DTaP vaccine to detox- ify the pertussis toxin. Pricing is not the only impediment to wider vaccine development and usage. Bombelles notes that adequate safeguards for intellectual property rights are crucial. Strengthening of intellectual property laws in China, he says, made it easier for Merck (Whitehouse Station, NJ) to share some of its hepatitis B vaccine know-how with Chinese collaborators, enabling them to build up domestic vaccine manufacturing capacity. Another issue pivots on health-care pri- orities in developing countries. With more than 300 candidate vaccines "in the pipeline," developing countries "need to make resources available at the national level;' points out Ciro de Quadros, Nakaji- ma's special advisor for the WHO Global Program for Vaccines and Immunization. Institutions in such countries need to form "consortia to bring vaccine prices down and make sure these products are widely used." Jeffrey L. Fox Edible plant vaccines The first human clinical trial for an edible, plant-based vaccine could start at the beginning of 1997. A team headed by Charles Arntzen at the Boyce Thompson Institute for Plant Research (BTI, Ithaca, NY) is currently undertaking advanced preclinical research on a vaccine for diar- rhea that consists of raw transgenic pota- toes expressing an Escherichia coli enterotoxin LT-B subunit gene. If the work goes as planned, the vaccine could enter clinical trials on 12 volunteers at the Balti- more Vaccine Testing Center (Baltimore, MD) in the new year. The potato vaccine, may, however, be beaten to the market by more palatable or technically accessible alternatives. Arntzen's research and the similar work of Hilary Koprowski's group at Thomas Jef- ferson University (Philadelphia, PA) on plants that produce rabies and human immunodeficiency virus antigens are directed at producing edible vaccines for developing countries. "How would you expect [people in] Africa or Asia to be vacci- nated except by the oral route?" asks Koprowski. Plants are "the cheapest and the most accessible production method," he says, and they eliminate both the need for refrig- eration, needles, and trained medical staff, and the risks of pathogen-derived vaccines. The BT! potato vaccine has been shown to stimulate the production of specific an tien- terotoxin IgG and lgA in mice. The next pre- clinical hurdle for the vaccine is to show that it can protect mice against challenge with the E.coli toxin, or with E.coli itself. Even though the potato vaccine will be the first plant-based vaccine in human tri - als, it is still rea lly just a model system. Few people enjoy raw potatoes (altho ugh Charles Arntzen did as a ch ild , he told Nature Biotechnology). According to Arntzen's colleague, Hugh Mason, the first commercial edible plant vaccine will be in bananas. They are much more palatable, NATURE BIOTECHNOLOGY VOLUME 14 NOVEMBER 1996 WHO and UNICEF find vaccines too costly