Modified vaccinia Ankara vaccine expressing Marburg virus-like particles protects guinea pigs from lethal Marburg virus infection

Delphine C Malherbe; Arban Domi; Mary J Hauser; Michelle Meyer; Bronwyn M Gunn; Galit Alter; Alexander Bukreyev; Farshad Guirakhoo

doi:10.1038/s41541-020-00226-y

Modified vaccinia Ankara vaccine expressing Marburg virus-like particles protects guinea pigs from lethal Marburg virus infection

NPJ Vaccines. 2020 Sep 2;5(1):78. doi: 10.1038/s41541-020-00226-y. eCollection 2020.

Authors

Delphine C Malherbe^{1

2}, Arban Domi³, Mary J Hauser³, Michelle Meyer^{1

2}, Bronwyn M Gunn⁴, Galit Alter⁴, Alexander Bukreyev^#^{1

2

5}, Farshad Guirakhoo^#³

Affiliations

¹ Department of Pathology, University of Texas Medical Branch, Galveston, TX USA.
² Galveston National Laboratory, Galveston, TX USA.
³ GeoVax Inc., Atlanta, GA USA.
⁴ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA USA.
⁵ Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX USA.

^# Contributed equally.

Abstract

We introduce a new vaccine platform against Marburg virus (MARV) combining the advantages of the immunogenicity of a highly attenuated vaccine vector (Modified Vaccinia Ankara, MVA) with the authentic conformation of virus-like particles (VLPs). Our vaccine, MVA-MARV-VLP, expresses the minimal components of MARV VLPs: the envelope glycoprotein GP and the matrix protein VP40. Electron microscopy confirmed self-assembly and budding of VLPs from infected cells. Prime/boost vaccination of guinea pigs with MVA-MARV-VLP-elicited MARV-specific binding and neutralizing antibody responses. Vaccination also induced Fc-mediated innate immune effector functions including activation of NK cells and antibody-dependent phagocytosis by neutrophils and monocytes. Inoculation of vaccinated animals with guinea pig-adapted MARV demonstrated 100% protection against death and disease with no viremia. Therefore, our vaccine platform, expressing two antigens resulting in assembly of VLPs in the native conformation in vaccinated hosts, can be used as a potent vaccine against MARV.

Keywords: Biologics; Vaccines.