Herpes zoster mRNA vaccine elicits superior immune responses over licensed vaccines with a favorable safety profile in animal models.

Abstract

Herpes zoster, a painful rash that is commonly known as shingles, occurs when the varicella-zoster virus is reactivated from its latent state in neurons. The condition is more frequent among older or immunocompromised individuals. Although the licensed vaccine Shingrix® has demonstrated high efficacy against herpes zoster, its undesired reactogenicity and escalating global demand have necessitated the development of improved or novel VZV vaccines. In the present research, we developed a VZV mRNA vaccine candidate, LVRNA015, that contains sequence-optimized mRNA encoding modified glycoprotein E encapsulated in an ionizable lipid nanoparticle. Our results demonstrated that LVRNA015 exhibited robust humoral and cellular immune responses for over 9 months in BALB/c mice. The magnitude of these responses was significantly higher than that observed with live attenuated VZV. Notably, mice vaccinated with LVRNA015 exhibited significantly higher neutralizing antibody levels and antigen-specific T-cell cytokine production in comparison with those receiving Shingrix®. Additionally, LVRNA015 induced a long-lasting immunological memory response, as evidenced by detection of memory T cells at 7 months after the final immunization. To evaluate vaccine safety, acute and repeat-dose toxicity studies were performed in rats; no significant alterations in body weight or in hematological and biochemical markers were observed following LVRNA015 administration. Active systemic anaphylaxis tests in guinea pigs showed no hypersensitivity in LVRNA015-treated animals. These findings support the further advancement of LVRNA015 to clinical studies as a promising shingles vaccine.