This blog post is part of Sabin’s Vaccine IQ: Intro to Vaccine Research & Development series, in which experts from Sabin’s Vaccine R&D team give an introduction to how vaccines are made, explaining the stages of research, development and testing vaccine candidates must go through before they are ready for distribution and use in the general population.
In this video, Dr. Rong Xu, Vice President of Non-Clinical Development at Sabin, explains some of the pre-clinical studies that vaccine candidates must go through to ensure they are safe, immunogenic and effective before they can be given to human volunteers in clinical trials.
Pre-clinical studies are required by regulatory agencies, such as the U.S. Food and Drug Administration (FDA), to safely move a vaccine candidate from the laboratory to the clinic, and include a range of assessments such as immunogenicity, toxicity, biodistribution and efficacy. These studies provide important pre-clinical information about the immune response, effective doses, and an early assessment of safety.
In vaccine research, immunogenicity refers to the ability of a vaccine candidate to elicit an immune response. Pre-clinical immunogenicity studies are designed to make initial assessments by studying vaccine candidates in animals such as mice, rabbits or monkeys. Study results are used to make determinations about which candidates are the most promising, and the optimal vaccine doses and vaccination schedules.
Once researchers identify the best candidates to advance in the development process, they conduct toxicity studies to assess pre-clinical safety. Toxicity studies are typically conducted in animals such as rabbits or rats. After receiving an injection of the vaccine candidate, the animals are observed for changes in body weight, temperature, or other clinical indications, as well as tissue pathology that suggests the vaccine could be harmful. The data obtained in toxicity studies, combined with the immunogenicity data, enables researchers to determine whether the vaccine candidate is reasonably effective and safe to proceed to human clinical trials.
Biodistribution studies provide additional safety data and are designed to assess how a vaccine distributes throughout the body and how quickly it is cleared from blood and tissues. These studies contribute to understanding the safety profile of the candidate since it is important that the body can successfully process and clear the vaccine after administration.
If a vaccine candidate demonstrates positive results in the immunogenicity and safety studies, it moves on to pre-clinical efficacy studies. Efficacy studies, also called proof of concept studies, test whether the vaccine protects against the infection and disease in question. Researchers assess efficacy by injecting the vaccine candidate into animals that are known to develop disease like that seen in humans. Next, animals are exposed to the pathogen to determine whether the vaccine provides effective protection.
Pre-clinical vaccine studies can take a few years to complete in order to collect sufficient safety and efficacy data. However, not all pre-clinical studies need to be completed before clinical trials begin. Some may be conducted concurrently with clinical trials. As an example, reproductive toxicity studies to assess vaccine safety for pregnant women can be conducted alongside early clinical trials
Finding the best and safest vaccine candidate to protect against a disease is a rigorous and time-consuming process. During the pre-clinical studies, a great deal of work goes into studying vaccine candidates before they are introduced to humans in clinical trials. Only after numerous pre-clinical studies demonstrate satisfactory results will regulatory agencies, such as the U.S. Food and Drug Administration (FDA), allow the vaccine candidates to proceed to testing in human clinical trials.