PMID- 32075939 OWN - NLM STAT- MEDLINE DCOM- 20201019 LR - 20201019 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 94 IP - 9 DP - 2020 Apr 16 TI - A Bivalent, Spherical Virus-Like Particle Vaccine Enhances Breadth of Immune Responses against Pathogenic Ebola Viruses in Rhesus Macaques. LID - 10.1128/JVI.01884-19 [doi] LID - e01884-19 AB - The 2013-2016 Ebola outbreak in West Africa led to accelerated efforts to develop vaccines against these highly virulent viruses. A live, recombinant vesicular stomatitis virus-based vaccine has been deployed in outbreak settings and appears highly effective. Vaccines based on replication-deficient adenovirus vectors either alone or in combination with a multivalent modified vaccinia Ankara (MVA) Ebola vaccine also appear promising and are progressing in clinical evaluation. However, the ability of current live vector-based approaches to protect against multiple pathogenic species of Ebola is not yet established, and eliciting durable responses may require additional booster vaccinations. Here, we report the development of a bivalent, spherical Ebola virus-like particle (VLP) vaccine that incorporates glycoproteins (GPs) from Zaire Ebola virus (EBOV) and Sudan Ebola virus (SUDV) and is designed to extend the breadth of immunity beyond EBOV. Immunization of rabbits with bivalent Ebola VLPs produced antibodies that neutralized all four pathogenic species of Ebola viruses and elicited antibody-dependent cell-mediated cytotoxicity (ADCC) responses against EBOV and SUDV. Vaccination of rhesus macaques with bivalent VLPs generated strong humoral immune responses, including high titers of binding, as well as neutralizing antibodies and ADCC responses. VLP vaccination led to a significant increase in the frequency of Ebola GP-specific CD4 and CD8 T cell responses. These results demonstrate that a novel bivalent Ebola VLP vaccine elicits strong humoral and cellular immune responses against pathogenic Ebola viruses and support further evaluation of this approach as a potential addition to Ebola vaccine development efforts.IMPORTANCE Ebola outbreaks result in significant morbidity and mortality in affected countries. Although several leading candidate Ebola vaccines have been developed and advanced in clinical testing, additional vaccine candidates may be needed to provide protection against different Ebola species and to extend the durability of protection. A novel approach demonstrated here is to express two genetically diverse glycoproteins on a spherical core, generating a vaccine that can broaden immune responses against known pathogenic Ebola viruses. This approach provides a new method to broaden and potentially extend protective immune responses against Ebola viruses. CI - Copyright (c) 2020 American Society for Microbiology. FAU - Singh, Karnail AU - Singh K AD - Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA Karnail.Singh@cchmc.org. AD - Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. AD - Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA. FAU - Marasini, Bishal AU - Marasini B AD - Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. FAU - Chen, Xuemin AU - Chen X AD - Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA. FAU - Ding, Lingmei AU - Ding L AD - Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. FAU - Wang, Jaang-Jiun AU - Wang JJ AD - Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. AD - Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. AD - Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA. FAU - Xiao, Peng AU - Xiao P AD - University of Louisiana at Lafayette, New Iberia Research Center, New Iberia, Louisiana, USA. FAU - Villinger, Francois AU - Villinger F AD - University of Louisiana at Lafayette, New Iberia Research Center, New Iberia, Louisiana, USA. FAU - Spearman, Paul AU - Spearman P AD - Division of Infectious Diseases, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. AD - Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. AD - Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200416 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (Ebola Vaccines) RN - 0 (Glycoproteins) RN - 0 (Vaccines, Attenuated) RN - 0 (Vaccines, Virus-Like Particle) RN - 0 (Viral Envelope Proteins) RN - 0 (Viral Vaccines) SB - IM MH - Africa, Western MH - Animals MH - Antibodies, Neutralizing/immunology MH - Antibodies, Viral/immunology MH - Disease Models, Animal MH - Ebola Vaccines/*immunology MH - Ebolavirus/*immunology MH - Female MH - Glycoproteins/immunology MH - Hemorrhagic Fever, Ebola/*immunology MH - Immunization MH - Macaca mulatta MH - Male MH - Vaccination MH - Vaccines, Attenuated MH - Vaccines, Virus-Like Particle/immunology MH - Viral Envelope Proteins/immunology MH - Viral Vaccines/immunology PMC - PMC7163155 OTO - NOTNLM OT - Bundibugyo virus OT - Ebola glycoprotein OT - Ebola vaccine OT - Ebola virus OT - Ebola virus disease OT - Marburg virus OT - Sudan virus OT - Tai Forest virus OT - virus-like particles EDAT- 2020/02/23 06:00 MHDA- 2020/10/21 06:00 PMCR- 2020/10/16 CRDT- 2020/02/21 06:00 PHST- 2019/11/05 00:00 [received] PHST- 2020/02/13 00:00 [accepted] PHST- 2020/02/23 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2020/02/21 06:00 [entrez] PHST- 2020/10/16 00:00 [pmc-release] AID - JVI.01884-19 [pii] AID - 01884-19 [pii] AID - 10.1128/JVI.01884-19 [doi] PST - epublish SO - J Virol. 2020 Apr 16;94(9):e01884-19. doi: 10.1128/JVI.01884-19. Print 2020 Apr 16.