Baculovirus Vector-Based Varicella-Zoster Virus Vaccine as a Promising Alternative with Enhanced Safety and Therapeutic Functions

Abstract

Varicella-zoster virus (VZV) poses lifelong risks, causing varicella and herpes zoster (HZ, shingles). Currently, varicella and HZ vaccines are predominantly live attenuated vaccines or adjuvanted subunit vaccines utilizing VZV glycoprotein E (gE). Here, we propose our vaccine candidates involving a comparative analysis between recombinant baculoviral vector vaccines (AcHERV) and a live attenuated vaccine strain, vOka. AcHERV vaccine candidates were categorized into groups encoding gE only, VZV glycoprotein B (gB) only, or both gE and gB (gE-gB) as AcHERV-gE, AcHERV-gB, and AcHERV-gE-gB, respectively. Humoral immune responses were evaluated by analyzing total IgG, IgG1, IgG2a, and neutralizing antibodies. Cell-mediated immunity (CMI) responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and Th1/Th2/Th17 cytokine profiling. In the mouse model, AcHERV-gE-gB elicited similar or higher total IgG, IgG2a, and neutralizing antibody levels than vOka and showed robust VZV-specific CMI responses. From the perspective of antigens encoded in vaccines and their relationship with CMI response, both AcHERV-gB and AcHERV-gE-gB demonstrated results equal to or superior to AcHERV-gE, encoding only gE. Taken together, these results suggest that AcHERV-gE-gB can be a novel candidate for alleviating risks of live attenuated vaccine-induced latency and effectively preventing varicella during early stages of life while providing strong CMI for effective resistance against HZ and therapeutic potential in later stages of life.