Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges.
The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guinea pigs. Significantly, guinea pigs vaccinated with at least 5 x 10(7) pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV.
Wang
Danher
D
Division of Bio-defense Vaccines, GenPhar Inc., 871 Lowcountry Blvd., Mount Pleasant, SC 29464, USA.
Hevey
Michael
M
Juompan
Laure Y
LY
Trubey
Charles M
CM
Raja
Nicholas U
NU
Deitz
Stephen B
SB
Woraratanadharm
Jan
J
Luo
Min
M
Yu
Hong
H
Swain
Benjamin M
BM
Moore
Kevin M
KM
Dong
John Y
JY
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D002522:Chlorocebus aethiops; D004306:Dose-Response Relationship, Immunologic; D046129:Ebola Vaccines / Q000008:administration & dosage* / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008379:Marburg Virus Disease / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D029024:Marburgvirus / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D016415:Sequence Alignment; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000096:biosynthesis* / Q000235:genetics; D014760:Viral Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics
D000914:Antibodies, Viral; D000956:Antigens, Viral; D046129:Ebola Vaccines; C081324:GP-protein, Marburg virus; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins