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Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine.
Gebre, Makda S; Rauch, Susanne; Roth, Nicole; Yu, Jingyou; Chandrashekar, Abishek; Mercado, Noe B; He, Xuan; Liu, Jinyan; McMahan, Katherine; Martinot, Amanda; Martinez, David R; Giffin, Victoria; Hope, David; Patel, Shivani; Sellers, Daniel; Sanborn, Owen; Barrett, Julia; Liu, Xiaowen; Cole, Andrew C; Pessaint, Laurent; Valentin, Daniel; Flinchbaugh, Zack; Yalley-Ogunro, Jake; Muench, Jeanne; Brown, Renita; Cook, Anthony; Teow, Elyse; Andersen, Hanne; Lewis, Mark G; Boon, Adrianus C M; Baric, Ralph S; Mueller, Stefan O; Petsch, Benjamin; Barouch, Dan H.
  • Gebre MS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Rauch S; CureVac AG, Tübingen, Germany. Susanne.rauch@curevac.com.
  • Roth N; CureVac AG, Tübingen, Germany.
  • Yu J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Chandrashekar A; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Mercado NB; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • He X; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Liu J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • McMahan K; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Martinot A; Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, USA.
  • Martinez DR; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Giffin V; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Hope D; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Patel S; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Sellers D; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Sanborn O; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Barrett J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Liu X; Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Cole AC; Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Pessaint L; Bioqual, Rockville, MD, USA.
  • Valentin D; Bioqual, Rockville, MD, USA.
  • Flinchbaugh Z; Bioqual, Rockville, MD, USA.
  • Yalley-Ogunro J; Bioqual, Rockville, MD, USA.
  • Muench J; Bioqual, Rockville, MD, USA.
  • Brown R; Bioqual, Rockville, MD, USA.
  • Cook A; Bioqual, Rockville, MD, USA.
  • Teow E; Bioqual, Rockville, MD, USA.
  • Andersen H; Bioqual, Rockville, MD, USA.
  • Lewis MG; Bioqual, Rockville, MD, USA.
  • Boon ACM; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Baric RS; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Mueller SO; CureVac AG, Tübingen, Germany.
  • Petsch B; CureVac AG, Tübingen, Germany.
  • Barouch DH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. dbarouch@bidmc.harvard.edu.
Nature ; 601(7893): 410-414, 2022 01.
Article in English | MEDLINE | ID: covidwho-1521758
ABSTRACT
The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 µg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines, Synthetic / Immunogenicity, Vaccine / COVID-19 Vaccines / COVID-19 / Nucleosides Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals Language: English Journal: Nature Year: 2022 Document Type: Article Affiliation country: S41586-021-04231-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines, Synthetic / Immunogenicity, Vaccine / COVID-19 Vaccines / COVID-19 / Nucleosides Type of study: Randomized controlled trials Topics: Vaccines / Variants Limits: Animals Language: English Journal: Nature Year: 2022 Document Type: Article Affiliation country: S41586-021-04231-6