Therapeutic Vaccines – Regulatory Challenges for Non-Clinical Development
Author:
Stephen Kirk
Principal Consultant
Introduction
Therapeutic vaccines differ from traditional prophylactic vaccines in that they are not targeted to a foreign antigen/protein but instead are intended to modulate the host immune system to endogenously present antigens and are routinely administered after an infection, cancer or other chronic disease state is established. This means that they can potentially target non-communicable diseases such as cancer, Alzheimer’s disease and cardiovascular disease etc, which now constitute the majority of treatable deaths including areas such as sub-Saharan Africa, where previously communicable diseases were the biggest threat to health. (Bigna, 2019).
They differ from traditional drug therapies in that they are focussed on altering the immune system by reinforcing, broadening, redirecting or curbing the hosts response instead of targeting the cause or the result of the condition itself. As a result of their mode of action they are considered immunotherapies and often intended for use in conjunction with other drug therapies or as an alternative when drugs have shown to be lacking in efficacy, displaying adverse side effects or when drug resistance is observed. Development of a successful therapeutic vaccine requires an understanding of various immune correlates including selection of target antigens, understanding the immune status in the disease state (tolerance or polarisation of the immune system) and potential adverse effects associated with induction of an immune response in situations where immunopathology exists resulting from a chronic disease state and sometimes altered immune state in the patient (Hill and Richards, 2022). Selection of target antigen, for a novel vaccine, takes on greater importance if the antigen is expressed by host cells (e.g for anti-cancer vaccines) and developers need to be aware of potential consequences if the same antigen (or similar) is also expressed by non-malignant cells elsewhere in the body.