Vaccine Research Priorities
In the past two decades new advances in biotechnology have resulted in the licensure of new vaccines, such as Hib, acellular pertussis, HepB, and attenuated varicella. Research institutions in the public sector have generated most of the basic scientific breakthroughs, whereas the large pharmaceutical companies have borne the cost for clinical development. Because such development requires heavy investments that need to be recouped from profits, new vaccines are expensive and therefore out of reach for poor populations.
Of all the vaccines currently under development, the three most needed today are vaccines to prevent the three big diseases—AIDS, TB, and malaria—which jointly account for more than 5 million deaths per year, or about 50 percent of all infectious disease deaths (see table 72.4). The total investment in vaccine against these diseases is not impressive, and it will probably take at least 5 to 10 years before a vaccine against any of them is available.
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GAVI has selected three vaccines for accelerated development: meningococcal meningitis, rotavirus, and pneumococcal vaccines. They have been selected because they are considered close to licensure, or "near term." Other important diseases are considered neglected in terms of vaccine development, among them shigella dysentery and dengue fever.
New diseases emerge and old ones reemerge, influencing priorities in vaccine research. The severe acute respiratory syndrome (SARS) epidemic, the outbreak of avian influenza, and the emergence of bioterrorism threats such as anthrax have led to a new search for vaccines against these infections. The threat of a pandemic of a reassorted influenza virus strain has recently highlighted the need for much greater resources and attention to be devoted to the development and distribution of effective flu vaccines.
New Vaccine Technologies
Alternative routes of administration would improve program safety, avoiding needle transmission of bloodborne pathogens. The ability of nonprofessionals to administer vaccines would also ease vaccine delivery strategies. New administration routes, such as oral, nasal, and transcutaneous routes, are being explored. An interesting project concentrates on the development of a nasal measles vaccine that would greatly enhance the feasibility of eliminating this disease by facilitating the administration during mass campaigns.
The concept of using plant-derived or edible vaccines involves encoding protective antigens from pathogens into transgenic plants. The plants are processed so that they can deliver a uniform dose of vaccines. Human clinical trials have been conducted with, for example, bananas and raw potatoes, which have shown encouraging antibody responses. The potential advantages of this technology could include thermostability, low investment needs, multivalency, and oral administration.
New Immunization Technologies
Priority is given to new delivery technologies that will expand access, improve safety, and cut the cost of immunization programs. They include the following technologies:
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The reuse of disposable syringes and needles is widespread and contributes significantly to the transmission of hepatitis B and C and HIV. The autodisabled syringe prevents reuse, and disposal in safety boxes reduces the risk to health staff and the general public from contaminated syringes and needles.
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Four different technologies are being explored to minimize the risk of infection from accidental exposure to sharps: corrosive disinfectants, thermoprocessing, needle destruction, and plastic melting. However, none of these options will soon be put into use in the field.
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Although the adoption of the multidose vial policy will contribute to the reduction of wastage, the ultimate aim is to provide all immunizations as monodose preparations. Injection devices prefilled with a monodose increase quality and safety at the point of use. UniJect is one such device that has been tested with HepB and tetanus toxoid. Village health workers or traditional birth attendants can use such devices. Currently, the cost of the device and the need for additional cold storage space when multidose presentation is exchanged for monodose pose obstacles to implementation.
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Needle-free injection devices deliver vaccine at high velocity into the skin without penetration of a needle, reducing the risk of transmission of bloodborne pathogens. Technologies are being developed for both mono- and multidose presentations. Available multidose injectors have not been found safe, and new models are under development. However, regulatory obstacles and high cost have rendered the monodose injector models that are currently available infeasible for large-scale programs.
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Vaccine distribution and storage without a cold chain would considerably simplify the delivery system, reduce cost, and allow for an integrated supplies mechanism. Development of vaccines that do not need a cold chain should be the highest priority for technology research. Sugar glass drying is one such technology that has shown great promise. It can be used to produce multivalent vaccines that are completely heat stable except under extreme climatic conditions. The high cost of regulation and licensing and the uncertainty about market prospects in industrial countries have so far impeded the development and use of this technology.
Obstacles to Vaccine Research
A host of obstacles confront vaccine research, the most important being the low level of investment for vaccine development when there are limited market prospects in the industrial world. Only a limited number of research centers have the capacity and experience required to conduct phase 2 and especially phase 3 trials of new vaccines, and they are mainly located in industrial countries. The capacity to conduct phase 3 trials in developing countries needs to be strengthened; the current situation impedes further development of vaccines needed in those countries.
Pilot lot production of vaccines is required for all phases of clinical trials. The global capacity to produce pilot lots is, however, inadequate to meet demand. Close public-private partnerships are necessary to ensure that the production capacity is available.
Manufacturers need markets to provide some assurance that the development cost for new products can be recouped. Such incentives require realistic forecasts of demands. Various mechanisms have recently been put in place to try to guarantee future markets, most notably the Vaccine Fund.
Last, disease burden data are needed for both selections of vaccines for national programs and for estimations of vaccine requirements, including market projections. However, such data are lacking in many countries and regions. Existing data are especially weak for respiratory disease of both bacterial and viral origin.
