A Single Dose of Modified Vaccinia Ankara expressing Ebola Virus Like Particles Protects Nonhuman Primates from Lethal Ebola Virus Challenge

Abstract

Ebola virus (EBOV), isolate Makona, was the causative agent of the West African epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013–2016. While several experimental vaccine and treatment approaches have been accelerated through human clinical trials, there is still no approved countermeasure available against this disease. Here, we report the construction and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara (MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein VP40 (MVA-EBOV). GP and VP40 form EBOV-like particles and elicit protective immune responses. In this study, we report 100% protection against lethal EBOV infection in guinea pigs after prime/boost vaccination with MVA-EBOV. Furthermore, this MVA-EBOV protected macaques from lethal disease after a single dose or prime/boost vaccination. The vaccine elicited a variety of antibody responses to both antigens, including neutralizing antibodies and antibodies with antibody-dependent cellular cytotoxic activity specific for GP. This is the first report that a replication-deficient MVA vector can confer full protection against lethal EBOV challenge after a single dose vaccination in macaques.

Ebola virus – prospects for a novel virus-like-particle-expressing modified vaccinia Ankara-based vaccine

“…Despite its abortive infection in primates, MVA has retained desirable features of its vaccinia parent: the elicitation of durable T cell and antibody (Ab) responses [12], the ability to be stored as a lyophilized product at ambient temperature (www.ClinicalTrials.gov; NCT00914732), and the ability to be used without an adjuvant. Due to its large genome size and the amount of coding capacity lost during adaptation (~20%), MVA can be used as a vector to express multiple vaccine antigens [13], a characteristic that readily supports the construction of recombinant MVAs expressing foreign virus-like particles (VLPs) [14][15][16]. Recently, promise for a safer and more stable vaccine has been demonstrated using MVA to express EBOV-like particles to achieve singledose protection in nonhuman primates [14].…”

“…Due to its large genome size and the amount of coding capacity lost during adaptation (~20%), MVA can be used as a vector to express multiple vaccine antigens [13], a characteristic that readily supports the construction of recombinant MVAs expressing foreign virus-like particles (VLPs) [14][15][16]. Recently, promise for a safer and more stable vaccine has been demonstrated using MVA to express EBOV-like particles to achieve singledose protection in nonhuman primates [14]. The advantage of this particular MVA vector compared to previously used vectors only expressing EBOV GP is that it expresses two EBOV antigens -the GP and the matrix protein VP40.…”

“…The advantage of this particular MVA vector compared to previously used vectors only expressing EBOV GP is that it expresses two EBOV antigens -the GP and the matrix protein VP40. Expression of both EBOV proteins from a MVA-infected cell leads to EBOVlike particle formation and the generation of a protective immune response [14,15]. The single-dose protection in nonhuman primates recently reported in Nature's Scientific Reports reflects this 'first in class' VLP vaccine benefitting from the choice of insertion sites and promoters and the careful design of the EBOV GP and VP40 transgenes used in its construction [14].…”

“…Expression of both EBOV proteins from a MVA-infected cell leads to EBOVlike particle formation and the generation of a protective immune response [14,15]. The single-dose protection in nonhuman primates recently reported in Nature's Scientific Reports reflects this 'first in class' VLP vaccine benefitting from the choice of insertion sites and promoters and the careful design of the EBOV GP and VP40 transgenes used in its construction [14]. Domi et al reported uniform protection of the MVA-EBOV vaccine when a single-dose was administered 28 days prior to lethal challenge with EBOV.…”

“…Domi et al reported uniform protection of the MVA-EBOV vaccine when a single-dose was administered 28 days prior to lethal challenge with EBOV. The animals developed good humoral immune responses including antigen-specific IgG and EBOV-neutralizing antibodies [14].…”