Abstract Herpes zoster (HZ) is a painful vesicular rash that occurs upon varicella-zoster virus (VZV) reactivation in older adults and immunocompromised individuals. Although there is currently an approved vaccine for the prevention of shingles, its administration is commonly associated with high reactogenicity. This highlights the need to develop new vaccine alternatives with long lasting immunity and improved tolerability upon administration. In the present study, 10 different vaccine candidate designs using two different codon optimizations targeting the VZV glycoprotein E (gE) were generated. A subset of mRNA constructs were formulated into lipid nanoparticles and assessed for their ability to induce specific cellular and humoral immune responses following vaccination in mice. Notably, the selected mRNA vaccine candidates induced high levels of antibodies and robust CD4+ but also CD8+ immune responses. Moreover, we showed that our alternate lyophilized vaccine provides comparable immunogenicity to current liquid frozen formulations and is stable under long-term storage conditions.
