• Vaccine Ontology ID: VO_0004389
• Type: DNA vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Macaque
• GP from Musoke Marburgvirus gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector rAd type 5 (rAd5) expressed GP of MARV (Geisbert et al., 2010).
  • Detailed Gene Information: Click Here.
• Vector: CMV/R and rAd type 5 (rAd5) (Geisbert et al., 2010)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004390
• Type: DNA vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Macaque
• GP from Musoke Marburgvirus gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector CMV/R expressed GP of MARV (Geisbert et al., 2010).
  • Detailed Gene Information: Click Here.
• Vector: CMV/R (Geisbert et al., 2010)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004387
• Type: DNA vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse, rabbit, guinea pig
• GP from Marburg virus Ravn gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector pWRG7077 expressed MARV Musoke GP in challenge study with macaques (Riemenschneider et al., 2003).
  • Detailed Gene Information: Click Here.
• Vector: pWRG7077 (Riemenschneider et al., 2003)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0011394
• Type: Recombinant vector vaccine
• Status: Research
• NP from Lake Victoria marburgvirus gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• Vector: An RNA replicon, based upon Venezuelan equine encephalitis (VEE) virus, was used as a vaccine vector (Hevey et al., 1998).
• Immunization Route: Subcutaneous injection

• Vaccine Ontology ID: VO_0004388
• Type: Recombinant vector vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Macaque
• GP from Musoke Marburgvirus gene engineering:
  • Type: Recombinant vector construction
  • Description: This DNA vaccine expressed MARV Musoke GP (Swenson et al., 2008).
  • Detailed Gene Information: Click Here.
• NP from Marburg virus Musoke gene engineering:
  • Type: Recombinant vector construction
  • Description: This DNA vaccine expressed MARV Musoke NP (Swenson et al., 2008).
  • Detailed Gene Information: Click Here.
• GP from Marburg virus Ci67 gene engineering:
  • Type: Recombinant protein preparation
  • Detailed Gene Information: Click Here.
• GP from Marburg virus Ravn gene engineering:
  • Type: Recombinant protein preparation
  • Detailed Gene Information: Click Here.
• NP gene engineering:
  • Type: Recombinant protein preparation
  • Detailed Gene Information: Click Here.
• GP gene engineering:
  • Type: Recombinant protein preparation
  • Detailed Gene Information: Click Here.
• SGP gene engineering:
  • Type: Recombinant protein preparation
  • Detailed Gene Information: Click Here.
• Vector: CAdVax (Swenson et al., 2008)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004391
• Type: Recombinant vector vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Guinea pig, macaques
• GP from Musoke Marburgvirus gene engineering:
  • Type: Recombinant vector construction
  • Description: Vector Venezuelan equine encephalitis (VEE) virus expressed the gene for MBGV GP (Hevey et al., 1998).
  • Detailed Gene Information: Click Here.
• Vector: Venezuelan equine encephalitis (VEE) virus (Hevey et al., 1998)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004566
• Type: Recombinant vector vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Guinea pig, macaques
• GP from Musoke Marburgvirus gene engineering:
  • Type: Recombinant protein preparation
  • Detailed Gene Information: Click Here.
• NP from Marburg virus Musoke gene engineering:
  • Type: Recombinant protein preparation
  • Detailed Gene Information: Click Here.
• Vector: Venezuelan equine encephalitis (VEE) virus (Hevey et al., 1998)
• Immunization Route: subcutaneous injection

• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: None
• Antigen: Ebola virus Mayinga Glycoprotein, Sudan Virus Gulu Glycoprotein, Marburg Virus Angola Glycoprotein (Tiemessen et al., 2022)
• GP from Zaire ebolavirus gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• GP Sudan ebolavirus gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• GP from Musoke Marburgvirus gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• NP from Tai Forest Ebolavirus gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• Vector: Tai Forest virus (MVA-BN-Filo) (Tiemessen et al., 2022)
• Preparation: This vaccine includes two doses with two different vaccine formulae - Ad26.Filo and MVA-BN-Filo. For Ad26.Filo , ..... Replication-incompetent, E1/E3-deleted recombinant adenoviral vectors based on Ad26 were engineered using the AdVac® system with the humanized GP DNA sequences for EBOV Mayinga (Ad26.ZEBOV), SUDV Gulu (Ad26.SUDV), and MARV Angola (Ad26.MARVA). The combination of these three Ad26 vectors in a 1:1:1 ratio will be further referred to as Ad26.Filo; MVA-BN-Filo is a recombinant, modified vaccinia Ankara-vectored vaccine, non-replicating in human cells, encoding the EBOV Mayinga, SUDV Gulu, and MARV Musoke GPs as well as the nucleoprotein of the Tai Forest virus. Adenovirus vaccines were given at 1.2 × 10^11 viral particles (vp; 4 × 10^10 vp/vector) and the MVA-BN-Filo vector at a dose of 5 × 10*8 infectious units (infU). MVA-BN-Filo is composed of the Tai Forest Virus. (Tiemessen et al., 2022).
• Immunization Route: Intramuscular injection (i.m.)
• Description: Two-dose regimen, consisting of Ad26.Filo followed by MVA-BN-Filo with an 8-week interval (Tiemessen et al., 2022)

• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: None
• Antigen: Marburg Virus (MARV) glycoprotein, MARV nucleoprotein, MARV Matrix Protein VP40 (Dye et al., 2016)
• VP40 gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• GP from Marburg virus Ravn gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• NP from Marburgvirus Ravn gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• Preparation: For a generation of the MARV VLPs, the MARV GP, NP and VP40 genes were inserted into a single baculovirus vector system for expression in insect cells Sf9 insect cells were infected with the single recombinant baculovirus, and the VLPs were recovered from the culture supernatants by high-speed centrifugation, purified on sucrose gradients, and resuspended in phosphate buffered saline (PBS), as previously described. Total proteins in the VLP preparations were determined and the VLPs were analyzed by SDS-PAGE/Western blotting and ELISA for filovirus protein content and identity, immunogenicity in mice and endotoxin levels. (Dye et al., 2016)
• Immunization Route: subcutaneous injection

• Type: Virus Like Particle
• Status: Research
• Host Species for Licensed Use: None
• Antigen: Marburg Virus (MARV) glycoprotein, MARV nucleoprotein, MARV Matrix Protein VP40 (Dye et al., 2016)
• VP40 gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• NP from Marburg virus Musoke gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• GP from Musoke Marburgvirus gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• Preparation: For a generation of the MARV VLPs, the MARV GP, NP and VP40 genes were inserted into a single baculovirus vector system for expression in insect cells Sf9 insect cells were infected with the single recombinant baculovirus, and the VLPs were recovered from the culture supernatants by high-speed centrifugation, purified on sucrose gradients, and resuspended in phosphate buffered saline (PBS), as previously described. Total proteins in the VLP preparations were determined and the VLPs were analyzed by SDS-PAGE/Western blotting and ELISA for filovirus protein content and identity, immunogenicity in mice and endotoxin levels. (Dye et al., 2016)
• Immunization Route: subcutaneous injection

• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: None
• Antigen: MARV Glycoprotein
• GP from Marburgvirus gene engineering:
  • Type: Recombinant vector construction
  • 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

• Vaccine Immune Response Type: VO_0000286
• Immune Response: The vaccine induced humoral responses , as well as CD4(+) and CD8(+) cellular immune responses, with skewing toward CD4(+) T-cell activity against MARV GP. The highest antibody titers were achieved with a heterologous prime-boost vaccine. rAd5-GP boosted titers in DNA-primed animals more than 2 orders of magnitude to a final prechallenge GP ELISA IgG titer of 1:237,167 (Geisbert et al., 2010).
• Efficacy: Heterologous prime-boost with DNA/rAd vectors generated protective immunity in all subjects after challenge with a lethal dose of MARV Angola (Geisbert et al., 2010).

Macaque Response

• Vaccine Immune Response Type: VO_0000286
• Immune Response: The DNA/DNA vaccine induced humoral responses comparable to those induced by a single inoculation with rAd5-GP, as well as CD4(+) and CD8(+) cellular immune responses, with skewing toward CD4(+) T-cell activity against MARV GP (Geisbert et al., 2010).
• Efficacy: The DNA-GP-only vaccine prevented death in all vaccinated subjects after challenge with a lethal dose of MARV Angola (Geisbert et al., 2010).

Macaque Response

• Vaccine Immune Response Type: VO_0000286
• Immune Response: All of the MARV GP DNA-vaccinated guinea pigs developed antibodies to MARV (Riemenschneider et al., 2003).
• Efficacy: In both studies (two different strains - Musoke and Ravn), two of three GP DNA-vaccinated monkeys were aviremic on the days assayed, and survived challenge, while one monkey in each study developed viremia levels similar to those of control monkeys and died. These results indicate that DNA vaccination alone is able to offer immunity to nonhuman primates, but suggest that the protective effect is near the threshold of vaccine efficacy (Riemenschneider et al., 2003).

Macaque Response

• Host Strain: Macaca fascicularis
• Vaccination Protocol: Twelve cynomolgus macaques (Macaca fascicularis), 11 females and 1 male, ranging from 2.8 to 4.5 kg, were inoculated subcutaneously with 10^7 FFU of VRP in a total volume of 0.5 ml at one site. Monkeys were anesthetized with ketamine, bled, and inoculated (as described for the first vaccine dose) 28 days after the primary injection, and again 28 days after the second (Hevey et al., 1998).
• Challenge Protocol: Animals were challenged 14 days after 3rd vaccine dose with 10^3.9 PFU MBGV
  subcutaneously (Hevey et al., 1998).
• Efficacy: MBGV NP afforded incomplete (partial) protection, sufficient to prevent death but not disease in two of three macaques (Hevey et al., 1998).

Macaque Response

• Vaccine Immune Response Type: VO_0000286
• Immune Response: All vaccinated animals from groups 1(challenged with 1,000 PFU MARV Musoke) and 2 (challenged with the same dose of ZEBOV) mounted strong antibody titers against all five filoviruses with similar kinetics (Swenson et al., 2005).
• Efficacy: Vaccination of NHP with CAdVax-Panfilo was 100% protective against challenge with multiple filovirus species, including ZEBOV, SEBOV, MARV Musoke, and MARV Ci67 (Swenson et al., 2005).

Macaque Response

• Vaccine Immune Response Type: VO_0000286
• Efficacy: Three monkeys vaccinated with replicons which expressed MBGV GP, and three others vaccinated with both replicons that expressed GP or NP, remained aviremic and were completely protected from disease (Hevey et al., 1998).

Macaque Response

• Vaccine Immune Response Type: VO_0003057
• Efficacy: Three monkeys vaccinated with replicons which expressed MBGV GP, and three others vaccinated with both replicons that expressed GP or NP, remained aviremic and were completely protected from disease (Hevey et al., 1998).

Macaque Response

• Vaccination Protocol: For that purpose, 16 cynomolgus macaques were assigned to four groups: one control group (n = 2) and three groups each receiving a different vaccine regimen (Table 2). The negative control group received an Ad26 empty vector followed by Tris buffer as dose 2. The three groups immunized with vaccine regimens received either Ad26.Filo, Ad35.Filo (n = 4); Ad26.Filo, MVA-BN-Filo (n = 5); or MVA-BN-Filo, Ad26.Filo regimen (n = 5). Adenovirus vaccines were given at 1.2 × 10^11 vp (4 × 10^10 vp/vector) and the MVA-BN-Filo vector at a dose of 5 × 108 infU. (Tiemessen et al., 2022)
• Immune Response: The MARV GP–specific antibody levels induced by the three different heterologous vaccine regimens were very similar 3 weeks post-dose 2 (study week 11). However, the MARV GP–specific antibody levels induced post-dose 1, at study weeks 4 and 8, were lower post-MVA compared to post-Ad26. Additionally, MARV-specific neutralizing antibodies could be detected in all immunized animals except for two animals in the MVA-BN-Filo, Ad26.Filo group.
• Side Effects: ne animal of the Ad26.Filo, MVA-BN-Filo regimen group (NHP 33841), that experienced transient severe clinical symptoms from day 8 until day 12 after infection, showed the lowest MARV GP–specific antibody concentration in serum at weeks 10 and 11 from the 5 animals in that group (2.45 and 2.26 EU/mL [log10]). MARV GP–specific binding antibody concentrations are good predictors for survival outcome after challenge, even when analyzed across various vaccination regimens. (Tiemessen et al., 2022)
• Challenge Protocol: Four weeks after dose 2, the animals were challenged i.m. with 1000 pfu MARV Angola. (Tiemessen et al., 2022)
• Efficacy: 21 days post-dose 2, 100% of participants on the active regimen responded to vaccination and exhibited binding antibodies against EBOV, SUDV, and MARV GPs. (Tiemessen et al., 2022)

Macaque Response

• Vaccination Protocol: Thirteen macaques received intramuscular injections in the caudal thigh muscle containing 3 mg (total protein) of MARV VLPs and 0.5 mg/kg of polyI:C adjuvant. The three control animals received injections of one of the adjuvants only. Immunizations were performed on study days 0, 42, and 84. (Dye et al., 2016)
• Immune Response: Cynomolgus macaques were vaccinated with MARV VLPs on study days 0, 42, and 84 and serum antibody titers against purified MARV GP and VP40 were determined for each animal every two to three weeks (study days 0, 14, 28, 42, 56, 70, 84 and 105). Control animals, which were vaccinated with polyI:C adjuvant alone, did not generate any antibody responses to either MARV GPdTM or VP40 (below the limit of detection at a 1:100 dilution of serum). The vaccinated animals exhibited similar kinetics of antibody responses to both antigens, with detectable antibody titers at day 14, which waned slightly at day 42 and increased again after the second and third vaccinations were administered on study days 42 and 84. Animals vaccinated with MARV VLPs with polyI:C exhibited similar responses to the protective GP antigens (p = 0.6006). Animals vaccinated with MARV VLPs and polyI:C had higher responses to the VP40 antigen than those vaccinated with MARV VLP and QS-21, specifically at the later time points of days 70, 84 and 105 post vaccination (p = 0.0057) (Dye et al., 2016)
• Side Effects: In Groups 1, 2 and 4, the macaques vaccinated with MARV VLPs and challenged via either aerosol or SQ route, there were no animals with visible clinical signs of filovirus infection. The adjuvant only control macaques presented with typical clinical signs of filovirus infection in macaques. Animal 16-P-S, which was vaccinated with polyI:C alone and challenged by the SQ route exhibited severe depression, moderate rash, and no food intake at day 10 post challenge. (Dye et al., 2016)
• Challenge Protocol: MARV was grown on Vero cells (6 total passages) and enumerated using standard plaque assay. Administration of the virus challenge was performed on study day 112 with the challenge material administered in the subcutaneous (SQ) tissues of the left thigh of each animal or via the aerosol route, as previously described. The target challenge dose for both SQ and aerosol exposure was 1000 plaque-forming units (pfu)/mL. For the SQ challenge, each macaque received 0.5 mL of challenge stock MARV-Musoke, which upon back-titration revealed an actual challenge dose of 315 pfu/macaque. For aerosol challenge, each macaque was exposed to 10 mL of challenge stock MARV-Musoke using a previously described methodology, and the air in the aerosolization chamber was sampled during each exposure to calculate the actual inhaled dose of virus that each animal received. This revealed that the inhaled dose ranged between 40–135 pfu/macaque. (Dye et al., 2016)
• Efficacy: Vaccination of cynomolgus macaques with MARV VLP with polyI:C adjuvant provided complete protection against challenge with aerosolized MARV-Musoke. (Dye et al., 2016)

Macaque Response

• Vaccination Protocol: Thirteen macaques received intramuscular injections in the caudal thigh muscle containing 3 mg (total protein) of MARV VLPs and 0.1 mg of QS-21 adjuvant. The three control animals received injections of one of the adjuvants only. Immunizations were performed on study days 0, 42, and 84.
• Immune Response: Cynomolgus macaques were vaccinated with MARV VLPs on study days 0, 42, and 84 and serum antibody titers against purified MARV GP and VP40 were determined for each animal every two to three weeks (study days 0, 14, 28, 42, 56, 70, 84 and 105). Control animals, which were vaccinated with QS-2 alone, did not generate any antibody responses to either MARV GPdTM or VP40 (below the limit of detection at a 1:100 dilution of serum). The vaccinated animals exhibited similar kinetics of antibody responses to both antigens, with detectable antibody titers at day 14, which waned slightly at day 42 and increased again after the second and third vaccinations were administered on study days 42 and 84. Animals vaccinated with MARV VLPs with QS-21 exhibited similar responses to the protective GP antigens (p = 0.6006). Animals vaccinated with MARV VLPs and polyI:C had higher responses to the VP40 antigen than those vaccinated with MARV VLP and QS-21, specifically at the later time points of days 70, 84 and 105 post vaccination (p = 0.0057) (Dye et al., 2016)
• Side Effects: In Groups 1, 2 and 4, the macaques vaccinated with MARV VLPs and challenged via either aerosol or SQ route, there were no animals with visible clinical signs of filovirus infection. The adjuvant only control macaques presented with typical clinical signs of filovirus infection in macaques. Both of the macaques that received QS-21 only (animals 11-Q-A and 15-Q-S) exhibited severe depression, widespread rash, and no food intake at day 10 post challenge. (
• Challenge Protocol: MARV was grown on Vero cells (6 total passages) and enumerated using standard plaque assay. Administration of the virus challenge was performed on study day 112 with the challenge material administered in the subcutaneous (SQ) tissues of the left thigh of each animal or via the aerosol route, as previously described. The target challenge dose for both SQ and aerosol exposure was 1000 plaque-forming units (pfu)/mL. For the SQ challenge, each macaque received 0.5 mL of challenge stock MARV-Musoke, which upon back-titration revealed an actual challenge dose of 315 pfu/macaque. For aerosol challenge, each macaque was exposed to 10 mL of challenge stock MARV-Musoke using a previously described methodology, and the air in the aerosolization chamber was sampled during each exposure to calculate the actual inhaled dose of virus that each animal received. This revealed that the inhaled dose ranged between 40–135 pfu/macaque. (Dye et al., 2016)
• Efficacy: Vaccination of cynomolgus macaques with MARV VLP with either QS-21 provided complete protection against challenge with aerosolized MARV-Musoke.(Dye et al., 2016)

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)