Therapeutic vaccines: challenges of chronic viral infections

Therapeutic vaccination is still a controversial subject regarding its potentially beneficial effects. It is often forgotten that therapeutic vaccination has been used for at least 40 years in modern medicine. Doctors treated allergies by administering the allergen by a different route and in a different form than when it causes the allergic reaction. The aim here was to modulate the direction of the host immune response from a ‘proallergic’ histamine releasing and T-helper 2-like response to an ‘antiallergic’ γIFN-producing T-helper 1-like response. Thus, the aim is to use the vaccine to deliver the antigen in a different way to modulate the host immune response. This is exactly the aim with a therapeutic vaccination of a chronic viral infection. A chronic viral infection has, depending on the virus, most probably modulated the host immune response to become less effective against the invading virus, thereby promoting viral persistence. Different viruses use different strategies to do this, and consequently, the therapeutic vaccine should be designed to remedy, correct, or at least partially modulate the host immune response in a more antiviral direction. There are no examples yet in human infections where a therapeutic vaccine has been found to undisputedly mediate a clearance of the infection. Numerous reports have suggested that the therapeutic vaccination did prime or reactivate immune responses, which may be regarded as more antiviral including γIFN-producing CD4+ T-helper cells and cytotoxic T lymphocytes. However, substantial hurdles need to be overcome before we have several therapeutically active vaccines, meaning that they indeed affect the disease progression and are commonly used in the clinic. These difficulties and problems are discussed in the present review.

Section editor:Charles Craig – Clinical Virology Specialist