Academic journal article Journal of Health Population and Nutrition

Translational Research to Assist Policy Decisions about Introducing New Vaccines in Developing Countries

Academic journal article Journal of Health Population and Nutrition

Translational Research to Assist Policy Decisions about Introducing New Vaccines in Developing Countries

Article excerpt

INTRODUCTION

The world is in the midst of a revolution in vaccine development, which is yielding a wide array of new approaches to vaccines and an increasing number of vaccines against newly-targeted diseases. Despite this, the movement of introduction of new and improved vaccines into the public-health programmes of developing countries has been painfully slow (1). This is most unfortunate since many of these new-generation vaccines, such as those against diarrhoea, meningitis, and pneumonia, are targeted against diseases that are major public-health problems in developing countries.

Much has been written about the scientific challenges of vaccine discovery and about strategies to improve the process of discovering new vaccine candidates. The financial hurdles and programmatic obstacles that impede the introduction of new vaccines in developing countries are also well-known. Less well-appreciated is the fact that, even for the existing vaccine candidates, there may be other formidable scientific challenges that can impede their introduction into public-health programmes in developing countries. The research agenda that address these challenges, which we term translational research, or research to translate experimental vaccine candidates into practical tools that are used in the public-health practice, is the subject of this issue of the Journal of Health, Population and Nutrition.

CLINICAL PARADIGM FOR EVALUATING VACCINES FOR LICENSURE

To place the rationale for translational research into context, it is helpful to describe the phases of clinical evaluation of vaccine candidates prior to licensure (2-3). Phase I trials are the initial human studies of a candidate; these are conducted when the candidate has shown promising results in pre-clinical evaluations. These trials are typically small in size (e.g. ca. 10-20 subjects), enroll healthy adult subjects, and are designed primarily to evaluate whether the vaccine is associated with frequent adverse effects. Phase 1 trials also typically evaluate other vaccine effects, such as immune responses and vaccine excretion (for live vaccine candidates) and may be used for determining an optimal dose and regimen for the vaccine candidate. Vaccine candidates found to be suitable in Phase 1 trials may be tested in Phase 2 trials. Phase 2 trials are distinguished by their larger sample sizes (often in the range of several hundred subjects); by their ability to evaluate, in a statistically meaningful fashion, immune responses and less common adverse reactions; and their eventual inclusion of subjects in the populations and age groups that will be the ultimate targets for the vaccine in public-health practice. Phase 2 trials may also measure excretion and transmissibility of live vaccines. Although Phase 2 trials are not typically designed to measure vaccine protection against the target infection, special types of Phase 2 trials, occasionally termed Phase 2b trials, are sometimes conducted to measure vaccine protection against experimental challenges with the target pathogen. Finally, for candidates found to be suitably safe and immunogenic in Phase 2 trials, Phase 3 trials may be mounted. The distinctive feature of Phase 3 trials is that they measure vaccine protection against naturally-occurring infections in populations at risk. Phase 3 trials are usually quite large, often enrolling thousands of subjects and are always conducted in the populations and age groups to be targeted by the vaccine. Because of their large sizes, Phase 3 trials are usually capable of detecting rather uncommon adverse events associated with vaccination. Moreover, because Phase 3 trials measure both immune responses to vaccination and vaccine protection, they may be able to correlate the two and thus to derive immunological correlates of protection. Phase 1 trials may be conducted in a controlled or uncontrolled fashion; Phase 2 and Phase 3 trials conventionally employ double-blind, randomized, controlled trial designs. …

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