TY - JOUR
T1 - A highly attenuated Vesiculovax vaccine rapidly protects nonhuman primates against lethal Marburg virus challenge
AU - Woolsey, Courtney
AU - Cross, Robert W.
AU - Agans, Krystle N.
AU - Borisevich, Viktoriya
AU - Deer, Daniel J.
AU - Geisbert, Joan B.
AU - Gerardi, Cheryl
AU - Latham, Theresa E.
AU - Fenton, Karla A.
AU - Egan, Michael A.
AU - Eldridge, John H.
AU - Geisbert, Thomas W.
AU - Matassov, Demetrius
N1 - Publisher Copyright:
© 2022 Woolsey et al. All rights reserved.
PY - 2022
Y1 - 2022
N2 - Background 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. Methodology/Findings 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-, Bcell-, and cytotoxic T-cell-type quantities. Conclusions/Significance 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.
AB - Background 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. Methodology/Findings 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-, Bcell-, and cytotoxic T-cell-type quantities. Conclusions/Significance 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.
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U2 - 10.1371/journal.pntd.0010433
DO - 10.1371/journal.pntd.0010433
M3 - Article
C2 - 35622847
AN - SCOPUS:85131772532
SN - 1935-2727
VL - 16
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 5
M1 - e0010433
ER -