Antigenicity and Vaccine Potential of Marburg Virus Glycoprotein Expressed by Baculovirus Recombinants

Abstract

There is no effective vaccine for Marburg virus (MBGV) or any other filovirus, nor enough pertinent information to expedite rational vaccine development. To ascertain some of the minimal requirements for a MBGV vaccine, we determined whether whole inactivated MBGV, or a baculovirus-expressed virion subunit, could be used to immunize guinea pigs against a lethal infection. Baculovirus recombinants were made to express the MBGV glycoprotein (GP) either as a full-length, cell-associated molecule or a slightly truncated (5.4%) product secreted into medium; the latter, for its far greater ease in manipulation, was tested for its vaccine potential. Like MBGV GP, both the full-length and truncated GP expressed by baculovirus recombinants were abundantly glycosylated with both N- and O-linked glycans; differences in glycosylation were detectable, but these could not be shown to affect antigenicity with respect to available antibodies. The recombinant truncated glycoprotein elicited protection against lethal challenge with the MBGV isolate from which it was constructed and less effectively against an antigenically disparate MBGV isolate. Killed (irradiated) MBGV antigen was protective, in a reciprocal fashion, against both MBGV types. In a preliminary assessment of possible protective mechanisms, serum antibodies from immune animals were shown to be sufficient for protecting naive guinea pigs from lethal MBGV infections

How Ebola and Marburg viruses battle the immune system

“…Support for the involvement of antibodies takes several forms. Foremost, passive immunotherapy with convalescent sera or monoclonal antibodies has been shown to mitigate or prevent MARV and ZEBOV disease in guinea pigs and mice [69][70][71][72] , delay viraemia and death in non-human primates 27 and possibly improve clinical outcomes in humans 73,74 . Moreover, B-cell-deficient mice were impaired in their ability to eliminate ZEBOV 75 .…”

Status and challenges of filovirus vaccines

“…When guinea pigs or cynomolgus macaques were vaccinated with VRP containing the GP from the Musoke strain of MARV, they were fully protected against subsequent s.c. inoculation with virulent Musoke [78]. In guinea pigs, there was no difference in the protection afforded by a one-, two-, or three-dose regimen.…”

“…Baculovirus-expressed MARV and ZEBOV GP have different glycosylation patterns than wild-type viruses [78,79]. Baculovirus-expressed MARV GP lacking the transmembrane domain (GP TM) was able to protect most guinea pigs when given with RIBI adjuvant and fully protected guinea pigs when given as a booster vaccination after a DNA prime [60].…”

“…Hevey et al [78] found that while GP alone conferred complete protection against MARV. NP alone did not.…”

“…In the 1995 outbreak of ZEBOV in Kikwit, blood transfusions from convalescent patients appeared to protect sick patients, suggesting that humoral immunity could protect [111] although these findings are controversial and the number of patients was limited. Studies using monoclonal antibodies and immune serum in cell culture and in animals have also suggested that antibody can protect against ZEBOV [18,20,53,78,112,113]. Hyper-immune equine sera, however, was unable to protect cynomolgus macaques from ZEBOV, although under some circumstances, it did delay viremia and time to death [114].…”