Abstract
Marburg virus (MARV) was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. Previous studies demonstrated that MARV virus-like particles (VLPs) containing the glycoprotein (GP), matrix protein VP40 and nucleoprotein (NP) generated using a baculovirus/insect cell expression system could protect macaques from subcutaneous (SQ) challenge with multiple species of marburgviruses. In the current study, the protective efficacy of the MARV VLPs in conjunction with two different adjuvants: QS-21, a saponin derivative, and poly I:C against homologous aerosol challenge was assessed in cynomolgus macaques. Antibody responses against the GP antigen were equivalent in all groups receiving MARV VLPs irrespective of the adjuvant; adjuvant only-vaccinated macaques did not demonstrate appreciable antibody responses. All macaques were subsequently challenged with lethal doses of MARV via aerosol or SQ as a positive control. All MARV VLP-vaccinated macaques survived either aerosol or SQ challenge while animals administered adjuvant only exhibited clinical signs and lesions consistent with MARV disease and were euthanized after meeting the predetermined criteria. Therefore, MARV VLPs induce IgG antibodies recognizing MARV GP and VP40 and protect cynomolgus macaques from an otherwise lethal aerosol exposure with MARV.
Highlights
The Filoviridae family consists of two genera of viruses denoted Ebolavirus and Marburgvirus, which are non-segmented, negative-strand RNA viruses
Less than 50 total cases of MARV or Ravn Marburgvirus (RAVV) were reported until a large outbreak having ~50% case mortality occurred during 1998–2000 in the Democratic Republic of Congo followed by a second outbreak in 2005 in Northern Angola where the case mortality rates were
Cynomolgus macaques were vaccinated with MARV virus-like particles (VLPs) (Figure 1) on study days 0, 42, and 84 and serum antibody titers against purified MARV GP and viral protein 40 (VP40) were determined for each animal every
Summary
The Filoviridae family consists of two genera of viruses denoted Ebolavirus and Marburgvirus, which are non-segmented, negative-strand RNA viruses. Filovirus infection of nonhuman primates and humans causes a highly lethal hemorrhagic fever disease with case mortality rates of 30%–90% [1]. Marburgviruses were named for the location of the first recognized filovirus outbreak that took place in Marburg, Germany in 1967. The outbreak originated in imported, infected monkeys from Uganda with. The Marburgvirus genus consists of two species, Marburg Marburgvirus (MARV) and Ravn Marburgvirus (RAVV) [4]. Less than 50 total cases of MARV or RAVV were reported until a large outbreak having ~50% case mortality occurred during 1998–2000 in the Democratic Republic of Congo followed by a second outbreak in 2005 in Northern Angola where the case mortality rates were
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