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Antigenicity and vaccine potential of Marburg virus glycoprotein expressed by baculovirus recombinants
M Hevey1, D Negley, J Geisbert
1Virology Division, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, Frederick, Maryland 21702, USA.
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
Insights
Developing a Marburg virus (MBGV) vaccine is crucial. A recombinant glycoprotein subunit showed protection against MBGV, suggesting a viable vaccine strategy.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- No effective vaccines exist for Marburg virus (MBGV) or other filoviruses.
- Limited information hinders rational vaccine development for MBGV.
Purpose of the Study:
- To assess minimal requirements for an MBGV vaccine.
- To determine if inactivated MBGV or a baculovirus-expressed subunit could immunize against lethal MBGV infection.
Main Methods:
- Baculovirus recombinants were engineered to express full-length or truncated MBGV glycoprotein (GP).
- The vaccine potential of a secreted, truncated GP was evaluated in guinea pigs.
- Animals were challenged with lethal doses of MBGV isolates.
Main Results:
- The truncated recombinant GP provided protection against the homologous MBGV isolate but was less effective against a disparate isolate.
- Killed (irradiated) MBGV antigen offered reciprocal protection against both MBGV types.
- Serum antibodies from immunized animals could protect naive guinea pigs from lethal MBGV infection.
Conclusions:
- A baculovirus-expressed truncated MBGV glycoprotein subunit can elicit protective immunity.
- Further research into MBGV vaccine development using subunit or inactivated virus approaches is warranted.
- Antibody-mediated immunity plays a significant role in protection against MBGV infection.