Immunobridging: A Vaccine Evaluation Methodology
Immunobridging is a methodology that uses immunological markers to infer vaccine efficacy by translating immunogenicity data from one population to predict protective effects in another population without conducting traditional efficacy trials.
Definition and Purpose
- Immunobridging is an approach used to infer the likelihood of a vaccine's protective effect by translating vaccine immunogenicity in humans to a protective effect, using the relationship between vaccine immunogenicity and the desired outcome in a suitable animal model or another human population 1.
- This methodology allows regulatory authorities to approve vaccines without conducting large-scale efficacy trials in every population, particularly when such trials would be impractical, unethical, or impossible 2.
Key Components of Immunobridging
- Immunobridging relies on identifying immune parameters (such as antibody levels) that correlate strongly with protection against disease 1.
- The process involves establishing a relationship between immune responses and protection in one population, then measuring the same immune responses in another population to predict efficacy 3.
- Binding antibodies against target antigens (like viral surface proteins) are often used as the immune parameter with the strongest correlation to protection 1.
Applications of Immunobridging
- Immunobridging is particularly valuable when:
- Traditional efficacy trials are challenging to conduct (as with Ebola virus vaccines) 1
- Extrapolating efficacy from one age group to another (e.g., from children to adults for dengue vaccines) 4
- Responding rapidly to emerging infectious diseases like COVID-19 2
- Protecting vulnerable populations who cannot participate in traditional efficacy trials 2
Regulatory Acceptance
- The International Coalition of Medicines Regulatory Authorities (ICMRA) has adopted immunobridging studies as acceptable for authorizing certain vaccines when efficacy data cannot be obtained 5.
- Multiple regulatory agencies, including the Taiwan Food and Drug Administration, have granted emergency use authorization based on immunobridging studies 5.
Methodology in Practice
- Immunobridging studies are designed to demonstrate equivalent immunogenicity between populations 3.
- The goal is to exclude clinically significant differences in immune response between:
- The population in whom efficacy was directly demonstrated
- The population to whom those efficacy results are being extrapolated 3
- Success criteria typically include geometric mean titer (GMT) ratios and sero-response rates that meet predetermined thresholds 5.
Advantages of Immunobridging
- Avoids duplication of large-scale efficacy trials 3
- Provides faster access to vaccines for populations in need 2
- Particularly valuable when correlates of protection are well-established 3
- Enables protection of vulnerable populations who cannot participate in traditional efficacy trials 2
Limitations and Considerations
- More controversial when immune correlates of protection are not well established 3
- Requires careful consideration of factors (ethnic or vaccine-related) that might influence vaccine efficacy 3
- The strength of immunobridging depends on the quality of the immunological marker selected as the correlate of protection 1
Immunobridging represents an important tool in modern vaccine development, allowing for more efficient approval processes while maintaining scientific rigor in evaluating vaccine effectiveness across diverse populations.