In the Virus-Like Particle Translational Oncology Laboratory, Qizhi Cathy Yao, M.D., Ph.D. is developing non-infectious HIV virus-like particles (VLPs) as candidate HIV mucosal vaccines for both preventive and therapeutic purposes. In preclinical studies, VLPs formed by structural proteins are highly immunogenic and capable of inducing protective immunity against various viral infections. We have modified vaccine immunogens into chimeric HIV VLPs which contain influenza viral surface glycoprotein HA or other immunologically functional molecules. We have shown that the chimeric HIV VLPs can induce enhanced humoral and cellular immune responses against HIV in a mouse model.
We have also studied the basic mechanisms of VLP-induced humoral and cellular immune responses, and other factors that affect these responses. For example, we found that VLP vaccines activate conventional B2 cells and promote B cell differentiation to IgG2a producing plasma cells; that VLP vaccines travel to the lymph nodes upon immunization and can be directly visualized by optical imaging techniques; and that intradermal immunization generates improved responses and might be a preferable delivery route for viral and cancer immunotherapeutic studies involving VLPs.
Since dendritic cells (DCs) have long been known to be pivotal in initiating immune responses, we are also interested in how VLPs modulate DC functions and will evaluate the efficacy of VLP-pulsed DC vaccines. In addition, we are testing the efficacy of modified chimeric VLP oral-mucosal immunization with novel vaccine adjuvants in non-human primates.