Q&A: The Role of Nonclinical Research and Immunobridging in Vaccine Development

For new vaccines, the path from concept to deployment is complex and rigorously controlled. Two foundational pillars in this process are nonclinical research and immunobridging. These interdependent methodologies are essential in evaluating the safety, efficacy, and immunogenicity of a vaccine prior to and during human clinical trials — especially when traditional trial structures aren’t feasible, as is the case with emerging pathogens or during public health emergencies. This Q&A provides a glimpse of the scientific principles, regulatory frameworks, and applied strategies underpinning these two critical components of vaccine development. 

Importance of nonclinical research 

Why is nonclinical research essential in vaccine development?

Nonclinical research helps assess vaccine safety, immune response, and potential effectiveness before and during clinical trials. It refines understanding of a vaccine’s immunogenicity and efficacy as human studies progress.  

What is pre-clinical research?

The term pre-clinical research applies more specifically to nonclinical research that needs to be done before clinical trials start. Pre-clinical can include, among other tasks, vaccine engineering and immunogenicity/efficacy screening of multiple candidates to select a lead for clinical trials.  

What does nonclinical testing involve?

It includes laboratory and animal studies to evaluate vaccine safety, immune response, and efficacy, as feasible. Optimal dosing in animal models can be established before human trials but the doses do not always apply for humans. Ultimately, a Phase 1 human clinical trial usually involves a dose-ranging design. 

Why are vaccines tested in animals before humans?

Animal studies help predict how a vaccine interacts with the immune system, show the potential effectiveness the vaccine, and provide information on safety. However, animal models must be carefully chosen to mimic human disease to be considered relevant and useful. 

Does nonclinical testing delay clinical trials?

Not usually. Nonclinical and clinical research can happen in parallel. Early nonclinical findings (such as the pre-clinical phase described above) provide support for a first-in-human or Phase 1 clinical trial. Ongoing animal studies that occur concurrently with the trial can be used to address unexpected results, better understand the mechanism of action, characterize the reproductive toxicity profile, and in some rare cases (such as with the Animal Rule), even be considered vital elements of establishing efficacy to support vaccine licensure.   

Animal Rule and Immunobridging 

How does immunobridging support vaccines for emerging disease threats or pandemics?

For diseases prone to outbreaks such as Marburg and Sudan ebolavirus (Sabin is currently working to advance vaccines for these diseases) where full-scale trials may be impractical due to unpredictable spread and duration, immunobridging can allow for faster vaccine evaluation by using immune response data rather than waiting for clinical outcomes. In a health emergency such as a pandemic, it also allows for quick updates to existing vaccines, demonstrating that new formulations trigger comparable immune responses. 

What is the FDA’s Animal Rule and why was it introduced?

A unique use of immunobridging is linking immune response and efficacy in animals to immune response in humans to infer vaccine efficacy. Under the FDA’s Animal Rule, introduced after the 2001 anthrax attacks, this approach supports vaccine licensure when human trials are not feasible. Approval relies on animal data showing a reasonable likelihood of efficacy in humans, alongside evidence of the vaccine’s mechanism of action. When possible, studies must use multiple animal models or a single well-characterized model that closely mimics human disease. 

Regulatory and Safety 

How are immunobridging and nonclinical research used in vaccine licensure?

Regulatory bodies such as the Food and Drug Administration (FDA), the European Medicines Agency, and the World Health Organization use immunobridging data to evaluate vaccine safety and effectiveness based on established immune markers that predict protection. This approach enables faster approvals while maintaining rigorous safety and efficacy standards, particularly for emerging disease threats or routine vaccine updates.

Agencies like the FDA and WHO evaluate data from nonclinical and human clinical studies to confirm safety, effectiveness, and manufacturing consistency before approving vaccines. 

Why does nonclinical research continue after vaccine approval?

Post-approval studies help explain unexpected clinical findings, investigate rare side effects, and improve formulations, ensuring vaccines remain safe and effective over time. Generally, a clinical study will also be needed to further evaluate learnings from nonclinical work.