A highly attenuated Vesiculovax vaccine rapidly protects nonhuman primates against lethal Marburg virus challenge

Marburg virus (MARV), an Ebola-like virus, remains an eminent threat to public health as demonstrated by its high associated mortality rate (23-90%) and recent emergence in West Africa for the first time. Although a recombinant vesicular stomatitis virus (rVSV)-based vaccine (Ervebo) is licensed for...

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Published in:PLoS neglected tropical diseases 2022-05, Vol.16 (5), p.e0010433-e0010433
Main Authors: Woolsey, Courtney, Cross, Robert W, Agans, Krystle N, Borisevich, Viktoriya, Deer, Daniel J, Geisbert, Joan B, Gerardi, Cheryl, Latham, Theresa E, Fenton, Karla A, Egan, Michael A, Eldridge, John H, Geisbert, Thomas W, Matassov, Demetrius
Format: Article
Language:English
Subjects:
Angola
Animals
Antibodies
Antibodies, Viral
Antigens
Arthralgia
Arthritis
Attenuation
Biology and life sciences
Care and treatment
Causes of
Clinical trials
Cytotoxicity
Dermatitis
Diagnosis
Disease control
Ebolavirus
Epidemics
Experiments
FDA approval
Glycoproteins
Health risks
Health surveillance
Hemorrhagic Fever, Ebola
Humans
Immunity
Immunization
Immunogenicity
Infections
Infectious diseases
Innate immunity
Laboratory animals
Lethal dose
Lethality
Lymphocytes B
Lymphocytes T
Macaca fascicularis
Marburg disease
Marburg virus disease
Marburg Virus Disease - prevention & control
Marburgvirus
Medicine and Health Sciences
Mortality
Natural killer cells
Plasmids
Prevention
Public health
Recombinants
Risk factors
Statistics
Stomatitis
Survival
Tropical diseases
Vaccines
Vaccines, Attenuated
Vasculitis
Vesiculovirus - genetics
Viral diseases
Viral replication
Viral Vaccines
Viruses
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Description
Summary:Marburg virus (MARV), an Ebola-like virus, remains an eminent threat to public health as demonstrated by its high associated mortality rate (23-90%) and recent emergence in West Africa for the first time. Although a recombinant vesicular stomatitis virus (rVSV)-based vaccine (Ervebo) is licensed for Ebola virus disease (EVD), no approved countermeasures exist against MARV. Results from clinical trials indicate Ervebo prevents EVD in 97.5-100% of vaccinees 10 days onwards post-immunization. Given the rapid immunogenicity of the Ervebo platform against EVD, we tested whether a similar, but highly attenuated, rVSV-based Vesiculovax vector expressing the glycoprotein (GP) of MARV (rVSV-N4CT1-MARV-GP) could provide swift protection against Marburg virus disease (MVD). Here, groups of cynomolgus monkeys were vaccinated 7, 5, or 3 days before exposure to a lethal dose of MARV (Angola variant). All subjects (100%) immunized one week prior to challenge survived; 80% and 20% of subjects survived when vaccinated 5- and 3-days pre-exposure, respectively. Lethality was associated with higher viral load and sustained innate immunity transcriptional signatures, whereas survival correlated with development of MARV GP-specific antibodies and early expression of predicted NK cell-, B-cell-, and cytotoxic T-cell-type quantities. These results emphasize the utility of Vesiculovax vaccines for MVD outbreak management. The highly attenuated nature of rVSV-N4CT1 vaccines, which are clinically safe in humans, may be preferable to vaccines based on the same platform as Ervebo (rVSV "delta G" platform), which in some trial participants induced vaccine-related adverse events in association with viral replication including arthralgia/arthritis, dermatitis, and cutaneous vasculitis.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0010433