• Vaccine Name: Recombinant VEE Replicons expressing MBGV GP
• Target Pathogen: Marburg Virus
• Target Disease: Hemorrhagic fever
• Vaccine Ontology ID: VO_0004125
• Type: Recombinant vector vaccine
• Antigen: Marburg virus (MBGV) GP (Hevey et al., 1998). An RNA replicon from Venezuelan equine encephalitis (VEE) virus was used as a vaccine vector. The VEE structural genes were replaced by genes for MBGV GP, nucleoprotein (NP), VP30, VP35, VP40, or VP24 (Hevey et al., 1998).
• GP from Musoke Marburgvirus gene engineering:
  • Type: Recombinant vector construction
  • Description: MBGV gene clone pGem-GP was provided by Heinz Feldmann and Anthony Sanchez (Centers for Disease Control and Prevention, Atlanta, GA). The MBGV GP gene from pGem-GP was excised with SalI and subcloned into the SalI site of a shuttle vector. A clone with the MBGV GP gene in the correct orientation was excised with ApaI and NotI, and this fragment was cloned into the ApaI and NotI sites of a VEE replicon plasmid (Hevey et al., 1998).
  • Detailed Gene Information: Click Here.
• NP from Marburgvirus Ravn gene engineering:
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click Here.
• VP30 gene engineering:
  • Type: Recombinant protein preparation
  • Description: An RNA replicon based on VEEV was used as the vector, with the VEE structural genes replaced by VP30. Function has yet to be determined; VP30 is found on the VP40 virion (Hevey et al., 1998).
  • Detailed Gene Information: Click Here.
• VP35 gene engineering:
  • Type: Recombinant protein preparation
  • Description: An RNA replicon based on VEEV was used as the vector, with the VEE structural genes replaced by VP35. Function has yet to be determined; VP35 is found on the VP40 virion (Hevey et al., 1998).
  • Detailed Gene Information: Click Here.
• VP40 gene engineering:
  • Type: Recombinant protein preparation
  • Description: An RNA replicon based on VEEV was used as the vector, with the VEE structural genes replaced by VP40. VP40 seems to serve as a matrix protein, affecting interactions between the nucleoprotein complex and lipid membrane. It is also the most abundant part of the virion (Hevey et al., 1998).
  • Detailed Gene Information: Click Here.
• VP24 gene engineering:
  • Type: Recombinant protein preparation
  • Description: An RNA replicon based on VEEV was used as the vector, with the VEE structural genes replaced by VP24. Function has yet to be determined; VP24 is found on the VP40 virion (Hevey et al., 1998).
  • Detailed Gene Information: Click Here.
• Preparation: Guinea pigs were inoculated with packaged recombinant VEE replicons expressing individual MBGV proteins and later injected with 10^3.3 LD50 guinea pig-adapted MBGV subcutaneously(Hevey et al., 1998).
• Virulence: MBGV NP protected all vaccinated guinea pigs from both death and viremia, while MBGV VP35 vaccination resulted in a majority of the animals surviving. Four of the five survivors were viremic 7 days after infection(Hevey et al., 1998).
  
• Description: Results indicated that VP35 afforded incomplete protection while either GP or NP were protective antigens(Hevey et al., 1998).

Monkey Response

• Host Strain: cynomolgus
• Vaccination Protocol: Several groups of macaques were tested: a group received VRPs that expressed MBGV NP; a group received VRPs that expressed MBGV GP; a group received a mixture of MBGV GP and MBGV NP VRPs; and a group received VRPs that expressed a control antigen (influenza HA)Anti-MBGV ELISA antibody titers were monitored throughout the experiment(Hevey et al., 1998).
• Persistence: Not noted.
• Immune Response: Animals inoculated with replicons that expressed MBGV proteins demonstrated prechallenge ELISA titers to purified MBGV antigen. Of the GP-vaccinated animals that survived challenge, a few demonstrated a modest boost in ELISA antibody titer (10- to 30-fold) when pre and postchallenge samples were compared. The surviving NP-inoculated macaques had larger boosts in ELISA antibody titers when pre- and
  postchallenge samples were compared. Some animals vaccinated with both GP and NP also demonstrated 100- to 300-fold rise in ELISA titers(Hevey et al., 1998).
• Side Effects: Not noted.
• Challenge Protocol: Monkeys recieved injections that expressed VEE replicons with either MBGV GP or MBGV NPor both(Hevey et al., 1998).
• Efficacy: All animals that received VEE replicons expressing MBGV GP, either alone or in combination with MBGV NP, survived challenge with 8000 PFU MBGV without any observed signs of illness(Hevey et al., 1998).