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

Monslow, Morgan A.; Elbashir, Sayda; Sullivan, Nicole L.; Thiriot, David S.; Ahl, Patrick; Smith, Jeff; Miller, Elise; Cook, James; Cosmi, Scott; Thoryk, Elizabeth; Citron, Michael; Thambi, Nithya; Shaw, Christine; Hazuda, Daria; Vora, Kalpit A.

doi:10.1016/j.vaccine.2020.06.062

Cited by 75Herpesvirus Infections and TreatmentsImmunotherapy and Immune ResponsesSARS-CoV-2 and COVID-19 Research

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

Monslow, Morgan A., Elbashir, Sayda, Sullivan, Nicole L., Thiriot, David S., Ahl, Patrick, Smith, Jeff, Miller, Elise, Cook, James +7 more·2020·Vaccine

DOI 10.1016/j.vaccine.2020.06.062

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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 AS01 B 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.

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Two RNA vaccine studies encoding other antigens did not observe durable antibody titers in humans or non-human primates.
“Two RNA vaccine studies encoding other antigens did not see durable antibody titers in humans or non-human primates”
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Authors: Monslow, M. A., Elbashir, S., Sullivan, N. L., Thiriot, D. S., Ahl, P., Smith, J., Miller, E., Cook, J., Cosmi, S., Thoryk, E., Citron, M., Thambi, N., Shaw, C., Hazuda, D., & Vora, K. A.
Affiliations: Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Moderna Therapeutics (United States) (US)
Corresponding author: Monslow, Morgan A.
Vora, Kalpit A.
ORCID: Elbashir, Sayda
Sullivan, Nicole L.
Ahl, Patrick
Cook, James
Thoryk, Elizabeth
Citron, Michael
Shaw, Christine
Hazuda, Daria
Vora, Kalpit A.
Venue: Vaccine
Publisher: Elsevier BV
Published: 2020-08
Volume: 38
Issue: 36
Pages: 5793-5802
ISSN: 0264-410X (ISSN-L)
DOI: 10.1016/j.vaccine.2020.06.062
OpenAlex: W3044891199
Cited by: 75
References: 39
Citations by year: 2026: 9 · 2025: 20 · 2024: 13 · 2023: 11 · 2022: 10 · 2021: 10 · 2020: 2
FWCI: 5.91
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Vaccine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords: varicella-zoster virus, herpes zoster vaccine, mRNA vaccines, lipid nanoparticle formulation, live attenuated vaccine, immunogenicity, humoral immune response, cell-mediated immunity, antibody persistence, nonhuman primate model, vaccine platform comparison, Zostavax, Shingrix
MeSH terms: Animals, Antibodies, Viral, Herpes Zoster, RNA, Messenger, Vaccines, Attenuated, Herpesvirus 3, Human, Viral Envelope Proteins, Vaccines, Subunit, Herpes Zoster Vaccine

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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

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