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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.
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.
Afiliação
  • Monslow MA; MRL, Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: morgan.monslow@merck.com.
  • Elbashir S; Moderna, Cambridge, MA, USA.
  • Sullivan NL; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Thiriot DS; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Ahl P; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Smith J; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Miller E; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Cook J; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Cosmi S; Eurofins Lancaster Laboratories Professional Scientific Services, Lancaster, PA, USA.
  • Thoryk E; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Citron M; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Thambi N; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Shaw C; Moderna, Cambridge, MA, USA.
  • Hazuda D; MRL, Merck & Co., Inc., Kenilworth, NJ, USA.
  • Vora KA; MRL, Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: kalpit.vora@merck.com.
Vaccine ; 38(36): 5793-5802, 2020 08 10.
Article em En | MEDLINE | ID: mdl-32703745
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacina contra Herpes Zoster / Herpes Zoster Limite: Animals Idioma: En Revista: Vaccine Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacina contra Herpes Zoster / Herpes Zoster Limite: Animals Idioma: En Revista: Vaccine Ano de publicação: 2020 Tipo de documento: Article