What is immunobridging?
What is the purpose of immunobridging?
Immunobridging schematic
Immunobridging and COVID-19
References
Further reading
Controlling the ever-evolving COVID-19 epidemic requires rapid vaccine development and rollout.
A vaccine cannot be lawfully disseminated in most countries without passing a thorough, placebo-controlled phase 3 efficacy trial. However, there have not been enough occurrences or volunteers in other locations to make this practicable.
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What is immunobridging?
Immunobridging is an alternative to traditional effectiveness trials that compares a vaccine candidate's immune response or protective correlates to those of a licensed vaccine.
It is the process of demonstrating that a vaccine candidate and an authorized vaccination produce similar immunological responses.
What is the purpose of immunobridging?
Bridging studies prevents the need for repeating large-scale effectiveness trials when expanding the clinical database of a novel vaccination to include more groups. When the immune response coincides with vaccination-induced immunity, data on immunogenicity may be extrapolated to findings on effectiveness.
Immunobridging is a regulatory and scientific strategy that compares immune response markers induced by a vaccination under different situations to estimate the vaccine's efficacy.
Immunobridging is used to infer vaccination effectiveness under one set of settings after its efficiency has been shown in a clinical endpoint efficacy study under different conditions.
Among them are the conditions in which the patient is not of the same age or demographic profile as those who participated in the efficacy study or are not receiving the same doses or following the same dosing schedule.
The conditions include newer versions of the same vaccination (including addition or modification of antigens), the combination with other immunizations to evaluate for immune interference and a distinct vaccine delivery system.
Immunobridging can help avoid requiring a new clinical endpoint efficacy study to be conducted where there is sufficient scientific justification to do so.
Immunobridging schematic
The immunobridging schematic consists of reference and test groups for study subjects. The reference group comprises the participants in a clinical trial where the treatment was effective. The formulation, dosing, and administration schedule of authorized vaccines are noted in this study.
The test group consists of the new participants who volunteer for the trials. The formulation, dosing, and administration schedule of authorized vaccines for this group is finalized based on the statistical hypothesis. The variables in the test group are usually kept similar to the reference group except for a few exceptions.
The hypothesis leads to the selection of immune markers. A normal antibody response is quantified using a tried-and-true test. The seroresponse (seroprotection) rate may be calculated using immunobridging analysis as a marker of immune response and is a reliable indicator of protection against illness.
Using clinically relevant but not scientifically proven indicators of the immune response to predict protection raises the possibility that immunobridging may be acceptable. The therapeutic significance of an immunological marker is conditional on the quality of the data supporting its use, and extra safeguards may be necessary to prevent faulty inferences.
To assess the spectrum of responses among study groups, researchers may use several endpoints on the same immunological marker (e.g., geometric mean titer to evaluate the higher end of the spectrum and seroresponse rate to evaluate the lower end of the spectrum).
Immunobridging and COVID-19
Various regulatory authorities agree that new COVID-19 vaccines may be approved based on a primary endpoint of neutralizing antibodies generated by an experimental vaccination compared to those authorized based on effectiveness.
Since conducting effective trials is becoming more difficult, this choice is more important than ever. An article published in the Vaccines Journal presents research that led to the emergency use authorization (EUA) for their candidate vaccine, MVC-COV1901, an adjuvanted protein subunit vaccine.
Research findings corroborate the suggestion of the International Coalition of Medicines Regulatory Authorities (ICMRA) that MVC-COV1901 is a better predictor of vaccination efficacy than AZD1222 based on Immunobridging.
When conducting efficacy trials is too costly or time-consuming, Immunobridging may be used as a substitute. In this retrospective study, researchers found that the protein subunit vaccine MVC-COV1901 produces an immunological response that is on par with or even better than that of AZD1222.
Because of this research, the candidate vaccine was granted an EUA in Taiwan. The consequences of these discoveries on the progress toward regulatory approval of vaccinations are substantial. Especially in poor and middle-income countries, this strategy may assist in increasing immunization rates and vaccine accessibility over time.
References
- Bockstal, V. et al. (2019) 'Immunobridging approach to assess clinical benefit as the basis for licensure of the monovalent Ebola vaccine', (115854), p. 115861.
- Doran Fink (2021) 'Immunobridging to Evaluate Vaccines', WHO meeting on COVID-19 Vaccines Research [Preprint].
- Estrada, J.A. et al. (2022) 'An Immunobridging Study to Evaluate the Neutralizing Antibody Titer in Adults Immunized with Two Doses of Either ChAdOx1-nCov-19 (AstraZeneca) or MVC-COV1901', Vaccines, 10(5), pp. 1–9. doi.org/10.3390/vaccines10050655.
Further reading
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