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. 2020 Aug 10;38(36):5793-5802.
doi: 10.1016/j.vaccine.2020.06.062. Epub 2020 Jul 20.

Immunogenicity generated by mRNA vaccine encoding VZV gE antigen is comparable to adjuvanted subunit vaccine and better than live attenuated vaccine in nonhuman primates

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Immunogenicity generated by mRNA vaccine encoding VZV gE antigen is comparable to adjuvanted subunit vaccine and better than live attenuated vaccine in nonhuman primates

Morgan A Monslow et al. Vaccine. .

Abstract

Shingles is a painful, blistering rash caused by reactivation of latent varicella-zoster virus (VZV) and most frequently occurs in elderly and immunocompromised individuals. Currently, two approved vaccines for the prevention of shingles are on the market, a live attenuated virus vaccine ZOSTAVAX® (Merck & Co., Inc., Kenilworth, NJ, USA) and an AS01B adjuvanted subunit protein vaccine Shingrix™ (Glaxo Smith Kline, Rockville, MD, USA). Human clinical immunogenicity and vaccine efficacy data is available for these two benchmark vaccines, offering a unique opportunity for comparative analyses with novel vaccine platforms and animal model translatability studies. The studies presented here utilized non-human primates (NHP) to evaluate humoral and cellular immune response by three vaccine modalities: the new platform of lipid nanoparticle (LNP) formulated mRNA encoding VZV gE antigen (VZV gE mRNA/LNP) as compared with well-established platforms of live attenuated VZV (VZV LAV) and adjuvanted VZV gE subunit protein (VZV gE protein/adjuvant). The magnitude of response to vaccination with a single 100-200 μg mRNA dose or two 50 μg mRNA doses of VZV gE mRNA/LNP were comparable to two 50 μg protein doses of VZV gE protein/adjuvant, suggesting the VZV gE mRNA/LNP platform has the potential to elicit a robust immune response, and both modalities generated markedly higher responses than VZV LAV. Additionally, the slopes of decay for VZV-specific antibody titers were roughly similar across all three vaccines, indicating the magnitude of peak immunogenicity was the driving force in determining immune response longevity. Finally, vaccine-induced immunogenicity with VZV LAV and VZV gE protein/adjuvant in NHP closely resembled human clinical trials immune response data for ZOSTAVAX® and Shingrix™, helping to validate NHP as an appropriate preclinical model for evaluating these vaccines.

Keywords: Adjuvanted subunit protein; Cellular and humoral immunity; Immune response durability; Live attenuate virus; Vaccine; Varicella-zoster virus; mRNA encoding antigen.

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Conflict of interest statement

Declaration of Competing Interest All authors are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, Moderna, Cambridge, MA, USA, and Eurofins Lancaster Laboratories Professional Scientific Services, Lancaster, PA, USA.

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