Modified mRNA-Based Vaccines Elicit Robust Immune Responses and Protect Guinea Pigs From Ebola Virus Disease

J Infect Dis. 2018 Jan 17;217(3):451-455. doi: 10.1093/infdis/jix592.

Abstract

Most current Ebola virus (EBOV) vaccine candidates are based on viral vectors, some of which cause side effects or require complex manufacturing. Modified mRNA vaccines are easily produced, safe, and are highly immunogenic. We developed 2 mRNA vaccines based on the EBOV envelope glycoprotein, which differed by the nature of signal peptide for improved glycoprotein post-translational translocation. The mRNAs were formulated with lipid nanoparticles to facilitate delivery. Vaccination of guinea pigs induced EBOV-specific IgG and neutralizing antibody responses and 100% survival after EBOV infection. The efficacy of our mRNA vaccine combined with preclinical safety data supports testing in clinical studies.

Keywords: Ebola virus; RNA; antibody response; immunization; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • Disease Models, Animal
  • Drug Carriers / administration & dosage
  • Ebola Vaccines / administration & dosage*
  • Ebola Vaccines / immunology*
  • Female
  • Guinea Pigs
  • Hemorrhagic Fever, Ebola / prevention & control*
  • Immunoglobulin G / blood
  • Liposomes / administration & dosage
  • RNA, Messenger / administration & dosage*
  • RNA, Viral / administration & dosage*
  • Survival Analysis

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Drug Carriers
  • Ebola Vaccines
  • Immunoglobulin G
  • Liposomes
  • RNA, Messenger
  • RNA, Viral