UCLA researchers in the Department of Molecular and Medical Pharmacology have a novel discovery showing the potential benefit of engaging complement-mediated antibody functions in future KSHV vaccine development.
BACKGROUND: Kaposi Sarcoma Associated Herpesvirus (KHSV) is the etiological agent for cancers such as Kaposi Sarcoma (KS) and primary effusion lymphoma. KHSV most frequently causes KS cancer. The American Cancer Society reports that KS develops from cells that line lymph or blood vessels and form colored blotches or tumors on the skin, called lesions, most commonly occurring in the legs, feet, or groin area. When these lesions start to form in the lungs, liver, or digestive tract, KS becomes life threatening. Although the occurrence of KS in the United States is low at about 4.5 cases per million people in 2017, the occurrence goes up 500 times for transplant patients and those with Human Immunodeficiency Virus (HIV). There is a need for a vaccine to alleviate the KS burden in the most affected populations.
INNOVATION: UCLA researchers led by Dr. Ting-Ting Wu have used the basic structure of herpesviruses, the fact they contain genes that encode a major capsid protein, a small capsid protein and glycoprotein, to develop novel methods for herpesviruses. Virus-like vesicles (VLVs) are membrane-enclosed vesicles that resemble native enveloped viruses, but lack the viral capsid. They are secreted alongside live virions during the lytic infection of herpesviruses including KSHV. UCLA researchers have produced mutant VLVs that contained a deletion of a portion of the major capsid protein and DNA packaging. Further, researchers showed that mice immunized with adjuvanted VLVs generated KSHV-specific T cell and antibody responses. Additionally, neutralization of KSHV infection by the VLV immune serum is enhanced in the presence of a complement system. This novel finding shows that vaccination induces antibody effector functions and can potentially improve infection-induced humoral immunity.
POTENTIAL APPLICATIONS:
- Inhibition and treatment of diseases caused by herpesviruses, such as KHSV.
- Enhancing complement-mediated neutralization of herpesviruses, such as KHSV.
ADVANTAGES:
- Used novel LNP-based adjuvants which are known to be potent adjuvants for protein-based vaccines.
- Observed a strong antibody response to ORF4, a complement regulatory protein.
DEVELOPMENT-TO-DATE: This technology has an associated peer-reviewed publication and a pending patent. This work has been shown in a mouse model.
Related Papers (from the inventors only): Lan, A.K., et al. Immunization of mice with virus-like vesicles of Kaposi Sarcoma-Associated Herpesvirus reveals a role for antibodies targeting ORF4 in activating complement-mediated neutralization. Journal of Virology. 2023.