Varicella zoster virus mRNA vaccine candidate induced superior cellular immunity and comparable humoral and Fc-mediated immunity compared to the licensed subunit vaccine in a mouse model

The threat of herpes zoster (HZ) is increasing, particularly in the elderly and immunocompromised individuals. Although two platform vaccines are currently available for HZ prevention, the low effectiveness of the live attenuated varicella-zoster virus vaccine (Zostavax®), and the high reactogenicity and limited supply of the AS01 adjuvant gE subunit vaccine (Shingrix®) indicate that, the development of more effective and safe vaccines is required. Compared to conventional vaccines, mRNA vaccines offer the advantages of faster production and generally do not require adjuvants. However, no authorized mRNA vaccine is currently available for HZ. Therefore, we aimed to prepare a gE mRNA vaccine and evaluate the immunogenicity compared with the two commercial vaccines in mice. The gE mRNA vaccine elicited a robust humoral immune response, as measured by an enzyme-linked immunosorbent assay and the fluorescent antibody to membrane antigen test. The mRNA vaccine binding antibody level was comparable to that of Shingrix® and significantly higher than that of Zostavax®. In contrast, in cellular immune responses, which were evaluated by ELISpot assays and intracellular cytokine staining assay, the VZV gE mRNA vaccine induced significantly higher responses than Zostavax® and Shingrix®. In addition, the antibody-dependent cellular phagocytosis activity of the gE mRNA vaccine was comparable to that of the commercial vaccines. However, the highest antibody-dependent cellular cytotoxicity response was achieved by Shingrix®, followed by gE mRNA and then Zostavax®. Our results demonstrate that the mRNA HZ vaccine candidate elicited robust immunogenicity, especially in cellular immunity, and shows a promising potential for HZ prevention.