De novo syntheses of Marburg virus antigens from adenovirus vectors induce potent humoral and cellular immune responses.
Marburg virus (MARV) is an African filovirus that causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, there are no MARV vaccines or therapies approved for human use. We hypothesized that developing a vaccine that induces a de novo synthesis of MARV antigens in vivo will lead to strong induction of both a humoral and cell-mediated immune response against MARV. Here, we develop and characterize three novel gene-based vaccine candidates which express the viral glycoprotein (GP) from either the Ci67, Ravn or Musoke strain of MARV. Immunization of mice with complex adenovirus (Ad)-based vaccine candidates (cAdVax vaccines), led to efficient production of both antibodies and cytotoxic T lymphocytes (CTL) specific to Musoke strain GP and Ci67 strain GP, respectively. Antibody responses were also shown to be cross-reactive across the MARV strains, but not cross-reactive to Ebola virus, a related filovirus. Additionally, three 1 x 10(8)pfu doses of vaccine vector were demonstrated to be safe in mice, as this did not lead to any detectable toxicity in liver or spleen. These promising results indicate that a cAdVax-based vaccine could be effective for induction of both humoral and cell-mediated immune responses to multiple strains of the Marburg virus.
Wang
Danher
D
Division of Biodefense Vaccines, GenPhar Inc., 871 Lowcountry Blvd., Mount Pleasant, SC 29464, USA.
Schmaljohn
Alan L
AL
Raja
Nicholas U
NU
Trubey
Charles M
CM
Juompan
Laure Y
LY
Luo
Min
M
Deitz
Stephen B
SB
Yu
Hong
H
Woraratanadharm
Jan
J
Holman
David H
DH
Moore
Kevin M
KM
Swain
Benjamin M
BM
Pratt
William D
WD
Dong
John Y
JY
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D003429:Cross Reactions; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D006801:Humans; D008099:Liver / Q000473:pathology; D008379:Marburg Virus Disease / Q000276:immunology / Q000517:prevention & control*; D029024:Marburgvirus / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D013154:Spleen / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; C081324:GP-protein, Marburg virus; D014759:Viral Envelope Proteins; D014765:Viral Vaccines