Traditional vaccines are made of either killed or live-attenuated viruses. Killed virus vaccines may suffer from weak immune responses and live attenuation is an inexact science that can take years. There has been an interest in developing alternative vaccine technologies. One class of vaccine technology that has shown promise is the subunit conjugate vaccine. In such vaccines only antigenically relevant portions of infectious agents are conjugated to a carrier capable of stimulating a stronger immune response. The use of virus-like particles as carriers in conjugate vaccines has shown promise, allowing for the targeting on non-traditional vaccine targets. In this dissertation we report on the use of the virus-like particle Qβ as a carrier in conjugate vaccines targeting cancer and Alzheimer’s disease. Cancer’s ability to escape the immune response requires a total immune response ensure that cancer does not mutate and return resistant to previously used immunotherapies. Previous use of Qβ-based conjugate vaccines against cancer have focused eliciting humoral responses. Herein we report lessons learned from the attempts to functionalize Qβ to elicit cellular immune response in a manner that would minimize the effect on a potential humoral response. Alzheimer’s disease is one of the most common causes of dementia and is hallmarked by the aggregation of tau. A Qβ-based conjugate vaccine targeting the tau-tau binding sites was synthesized and evaluated. Immunization generated a strong humoral immune response superior to a KLH-based conjugate vaccine targeting the same epitope. Generated antibodies were able to preferentially recognize disease associate forms of tau and stain tau in human tissue.
Read
