• Vaccine Name: Marburg Virus Vaccine rVSV-N4CT1-MARV-GP
• Target Pathogen: Marburg Virus
• Target Disease: Hemorrhagic fever
• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: None
• Antigen: MARV Glycoprotein
• GP from Marburgvirus gene engineering:
  • Type: Recombinant vector construction
  • Description:
  • Detailed Gene Information: Click Here.
• Preparation: An expression cassette encoding the full-length MARV-Angola GP was cloned into a plasmid containing the full-length VSV genome. This plasmid encodes for a VSV N1 to N4 gene translocation and VSV G CT1 truncation; the MARV-Angola GP or HIV gag gene is expressed from the first genomic position from the single 3’-proximal promoter site to maximize GP antigen expression. Vectors were then recovered from Vero cells following electroporation with the resulting plasmids along with VSV helper plasmids. The rescued virus was plaque purified and amplified to produce virus seed stocks.(Woolsey et al., 2022)
• Immunization Route: Intramuscular injection (i.m.)

Macaque Response

• Vaccination Protocol: Eighteen adult (9 females and 9 males) cynomolgus macaques (Macaca fascicularis) of Chinese origin (PreLabs, Worldwide Primates) ranging in age from 3 to 8 years and weighing 2.86 to 7.60 kg were used for three separate studies at the GNL. Macaques were immunized with a single 10 million PFU intramuscular (i.m.) injection of rVSV-N4CT1-MARV-GP at 7 (N = 5), 5 (N = 5), or 3 (N = 5) days prior to MARV exposure. Three animals were immunized with an identical dose of rVSVN4CT1-HIVgag at each respective time point to serve as non-specific controls. The inoculation was equally distributed between the left and right quadriceps. (Woolsey et al., 2022)
• Immune Response: Vaccinated survivors expressed greater development of MARV GP-specific antibodies and early expression of predicted NK cell-, B-cell-, and cytotoxic T-cell-type quantities. (Woolsey et al., 2022)
• Side Effects: Regardless of the rVSV vaccine vector administered, all fatal cases presented with typical MVD clinical signs such as fever, anorexia, dyspnea, macular rash, and/or depression. Specifically vaccinated survivors remained healthy and did not display clinical signs of disease other than anorexia at 5 DPI in one subject in the -7 group and transient anorexia and a mild petechial rash in the sole survivor in the -3 group. However, all survivors exhibited various hematological changes over the course of the study. Postmortem gross examination of fatal cases in both specifically and non-specifically vaccinated macaques revealed lesions consistent with MVD including subcutaneous hemorrhage; necrotizing hepatitis; splenomegaly; lymphadenitis; and hemorrhagic interstitial pneumonia (characterized as failure to completely collapse and multifocal reddening of the lungs). No significant lesions were detected in examined tissues of vaccinated survivors at the study endpoint. (Woolsey et al., 2022)
• Challenge Protocol: All macaques were challenged i.m. in the left quadriceps with a uniformly lethal 1000 PFU target dose of MARV-Angola (actual doses were 1475, 1475, and 1300 PFU, respectively). An internal scoring protocol was implemented to track disease progression in challenged animals. (Woolsey et al., 2022)
• Efficacy: Survival rates of groups immunized with rVSVN4CT1-MARV-GP were significantly different than the vector control group with 100% (log-rank test, p = 0.0046) and 80% (p = 0.0153) efficacy for -7 DPI and -5 DPI groups, respectively. No statistical difference (p = 0.5110) was noted for the -3 DPI vaccination group, although a sole subject (20%) survived. (Woolsey et al., 2022)
• Description: rVSV-N4CT1-MARV-GP-mediated protection appears to be at least partially attributed to tight control of virus replication and rapid stimulation of innate immunity. Resolution of the innate immune response coincided with development of adaptive immunity including the generation of MARV GP-specific immunoglobulins, and transcriptional evidence of recruitment of cytotoxic and effector cells. In contrast, non-specific vaccination led to the development of MVD with characteristic uncontrolled virus replication and transcriptional evidence of sustained innate immunity, complement dysregulation, and immune checkpoint expression. (Woolsey et al., 2022)