Vaccine R&D Process
All vaccine candidates must be put through a lengthy, rigorous process of scientific evaluation before they can be licensed for general use. This process is time consuming – it can take up to a decade just to move a candidate vaccine through the three phases of clinical development alone. But it is also indispensable. The clinical trials in which vaccines are evaluated ensure that licensed vaccines are safe, effective, and appropriate for the populations most likely to use them.
IAVI researchers have considerable experience in applied research for vaccine design, the translation of vaccine concepts into testable products, and the evaluation of such vaccine candidates in early-stage clinical trials. Here is an overview of the development process:
Preventive HIV vaccine development begins on the lab bench, with foundational research on HIV and its interaction with the immune system. Laboratories at academic centers and research institutes conduct the bulk of such research. Their discoveries inform the design of novel vaccine concepts.
Concepts derived from basic research are experimentally evaluated in the laboratory in the discovery and design phase. This applied research attempts to convert interesting concepts derived from basic research into potential vaccine candidates. The most promising HIV vaccine candidates are then further refined through a process called lead optimization where the candidates' characteristics, such as stability or potency, are improved through iterative refinement.
Preclinical research includes studies of the composition of vaccine candidates – as well as a preliminary examination – in animal models, of their ability to provoke an immune response. To move into the clinical phase of development, a candidate HIV vaccine must be shown in laboratory studies and animal models to be nontoxic, unlikely to cause other adverse reactions and, at a minimum, to provoke a vigorous immune response to the virus.
Manufacturing and Regulatory Review
Once a candidate is selected to move onto clinical trials, its production must be scaled up to be made consistently and in large enough volume. Particular care is given in this process to developing standardized methods to continually assess the quality and consistency of candidates during production. These methods, processes and studies – and the information compiled during the preclinical development of the candidate – are submitted to regulators, who determine whether a candidate product is fit for evaluation in clinical trials and can be safely given to human volunteers.
HIV vaccine candidates that pass preclinical muster then go through a rigorous, three-phase process of evaluation in human volunteers to ensure that they are safe and capable of preventing HIV infection.
- Phase I clinical trials are typically done with small groups, or cohorts, of volunteers, and principally test whether a candidate is safe for use in humans and produces an immune response
- Phase II trials further examine its safety in a larger cohort, and examine the scale and types of immune responses it provokes
- Phase IIb trials might also provide a preliminary evaluation of a candidate’s efficacy, or its ability to prevent HIV infection
- Phase III trials examine a candidate’s efficacy and safety in large cohorts, often including thousands of volunteers
If a Phase III trial establishes that a candidate can prevent HIV infection, the developer can submit data to regulators, who might agree to license the vaccine. Licensed vaccines are sometimes further evaluated following licensure, in what are known as Phase IV clinical trials. No HIV vaccines have yet been licensed.