Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges
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Published on: January 20, 2019
Danher Wang1, Michael Hevey, Laure Y Juompan
1Division of Bio-defense Vaccines, GenPhar Inc., 871 Lowcountry Blvd., Mount Pleasant, SC 29464, USA.
Abstract:
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.
Insights
A novel adenovirus-vectored vaccine (cAdVax) shows promise for preventing Marburg virus (MARV) infections. This trivalent vaccine protected guinea pigs against lethal MARV strains, offering a potential solution for this deadly hemorrhagic fever.
Area of Science:
- Virology
- Vaccinology
- Infectious Diseases
Background:
- Marburg virus (MARV) is a deadly African filovirus causing hemorrhagic fever with high mortality.
- Current Marburg virus disease treatment is supportive, with no available vaccines.
- There is a critical need for effective Marburg virus vaccines to prevent outbreaks.
Purpose of the Study:
- To develop and characterize a novel recombinant vaccine against Marburg virus.
- To evaluate the efficacy of a complex adenovirus-vectored vaccine (cAdVax) expressing a Marburg virus glycoprotein (GP) fusion protein.
Main Methods:
- A single complex adenovirus-vectored vaccine (cAdVaxM(fus)) was engineered to overexpress a Marburg virus GP fusion protein from Musoke and Ci67 strains.
- The vaccine's immunogenicity was assessed by measuring Marburg virus-specific antibodies in vaccinated mice and guinea pigs.
- Protective efficacy was determined by challenging vaccinated guinea pigs with lethal strains of Marburg virus.
Main Results:
- Vaccination with cAdVaxM(fus) elicited robust Marburg virus-specific antibody production in mice and guinea pigs.
- Guinea pigs vaccinated with a minimum of 5 x 10(7) plaque-forming units (pfu) of cAdVaxM(fus) achieved 100% protection against lethal Marburg virus challenge.
- The vaccine demonstrated trivalent protective efficacy against Musoke, Ci67, and Ravn strains of Marburg virus.
Conclusions:
- The cAdVaxM(fus) vaccine is a promising candidate for preventing Marburg virus infections.
- This novel vaccine offers potential for controlling multi-strain Marburg virus outbreaks.
- The development of this trivalent vaccine represents a significant advancement in Marburg virus preparedness.
