Vaccines: All Things Considered (original) (raw)

2006, Clinical and Vaccine Immunology

This minireview is based on the diverse discussions of vaccine development presented during the GTCBIO Third Annual Conference on Vaccines: All Things Considered (3 to 4 November 2005, Arlington, Va.). As the name implies, the meeting provided an excellent overview of the concepts and concerns for vaccine developers and the vaccine industry and was relevant to individuals in academia, industry, regulatory agencies, implementation, military, government, and physicians. This minireview is divided into the categories that the keynote speaker, Michel Klein (Canadian Network for Vaccines and Immunotherapeutics, Université de Montreal), indicated to be the basis for new vaccine development: (i) biological basis for vaccine development, (ii) new technologies, (iii) new targets, (iv) bringing a vaccine to market, and (v) current issues in vaccine development. Immunization programs have led to the elimination and/or control of several different infectious diseases, including smallpox, polio, measles, mumps, rubella, Haemophilus influenzae type B disease, pertussis, tetanus, and diphtheria. These vaccines were developed using technology from the 19th and 20th centuries, inactivation by heat, chemicals, and irradiation to produce a killed vaccine, vaccination with a serologically related virus à la Jenner, and attenuation by tissue culture passage to produce live vaccines with substantially reduced virulence. The vaccines of the 21st century will be developed by improvements on these basic techniques and through the use of new technologies based on the expanding understanding of the immune response. New, and still unmet, targets for vaccine development include some of the more difficult infectious agents, such as human immunodeficiency virus (HIV), cytomegalovirus, and severe acute respiratory syndrome coronavirus; bacteria, such as Pseudomonas aeruginosa, Neisseria gonorrhea, or Mycobacterium tuberculosis; and parasitic diseases, such as malaria or hookworm disease. In addition, vaccines will also be developed as therapies against disease for autoimmune diseases, cancer, hypertension, Alzheimer's dementia, contraception, and to promote the cessation of bad habits, such as smoking. Bioterrorism has brought renewed interest to new and largescale vaccine development. As Michael Moodie (Chemical and Biological Arms Control Institute) described in "Vaccines and National Security: the Need for a National Strategy," we have seen the evidence with fearsome examples that the threat of bioterrorism can be delivered by individuals or groups with religious, political, or bioterror agendas. Vaccines are an excellent, technically feasible defense against these threats with the potential to limit postattack disease spread. Vaccine readiness can even be considered a deterrent to the development and use of specific bioterror agents, because it reduces the potential for effectiveness and hence decreases its utility as a weapon. Even though vaccination is probably the most beneficial therapy that a physician can provide a patient, there are still significant roadblocks to the development and licensing of new vaccines. These roadblocks include biological and technological issues, but to a large extent, the major roadblocks are the difficulty in preparing a 100% safe and effective product, the high cost of testing, and the almost unavoidable consequence of the occasional, no matter how infrequent and how minor, adverse event. Development of a vaccine requires more than 500 million dollars, it takes a long time to get through phase III trials, and the profit margin for such an investment is 1/10 or less of that of a successful drug that must be taken on a daily basis, such as a cholesterol-lowering statin derivative. In addition, vaccines are administered to healthy individuals, and any side effects, even if unrelated to the vaccine, make the manufacturer a target for lawsuits. Even beyond development costs, vaccine programs are expensive, vaccines are perishable, and they must be administered by a professional and may not be accepted by the populace without a defined urgent microbial threat. Clearly there is a need for a vaccine strategy that is integrated, sustainable, flexible, and consistent. The challenge will be to develop new vaccines, new mechanisms for evaluating and funding vaccines, and even ways to administer the vaccines.