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Vaccine Comparison

Recombinant VEE Replicons expressing MBGV GP Recombinant VEE Replicons expressing MBGV NP VSV-based vaccine expressing MBGV GP
Vaccine Information Vaccine Information Vaccine Information
  • 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 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 gene engineering:
    • Type: Recombinant protein preparation
    • 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 103.3 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).
  • Vaccine Ontology ID: VO_0004126
  • Type: Recombinant vector vaccine
  • Antigen: Marburg virus (MBGV) nucleoprotein (NP) (Hevey et al., 1998).
  • NP from Marburg virus Musoke gene engineering:
    • Type: Recombinant protein preparation
    • Description: The ORF for the glycoproteins were generated by PCR and cloned into GP-lacking VSV vectors (Daddario-DiCaprio et al., 2006).
    • Detailed Gene Information: Click Here.
  • Preparation: A gene coding for a protein of interest is cloned in place of the VEE virus structural genes (Hevey et al., 1998).
  • Virulence: Without any observed signs of illness, all animals that received VEE replicons expressing MBGV GP, either alone or in combination with MBGV NP, survived challenge with 8000 PFU MBGV(Hevey et al., 1998).
  • Vaccine Ontology ID: VO_0004136
  • Type: Recombinant vector vaccine
  • Antigen: Marburg virus (MBGV) glycoprotein (GP) was used. A recombinant vesicular stomatitis virus (VSV) was used as a vector. The vaccine utilizes the VSVΔG/MARVGP-Musoke strain (Daddario-DiCaprio et al., 2006).
  • GP gene engineering:
    • Type: Recombinant protein preparation
    • Description: The ORF for the glycoproteins were generated by PCR and cloned into GP-lacking VSV vectors (Daddario-DiCaprio et al., 2006).
    • Detailed Gene Information: Click Here.
  • Preparation: The ORF for the glycoproteins for the MARV-Musoke and the ZEBOV were generated by PCR and cloned into GP-lacking VSV vectors. Infectious clones for the VSV Indiana serotype were used (Daddario-DiCaprio et al., 2006).
  • Virulence: All animals developed high anti-MARV IgG antibody levels by the challenge time, while low levels of anti-MARV neutralizing antibodies were observed for a large percentage of animals vaccinated with VSVΔG/MARVGP-Musoke at the challenge day. Protection of the host subjects injected with the VSVΔG/MARVGP-Musoke vaccine appears to be associated with humoral response, as opposed to cellular immune response (Daddario-DiCaprio et al., 2006).
Host Response Host Response Host Response

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).

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
  • 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).

Monkey Response

  • Host Strain: cynomolgus macaques
  • Vaccination Protocol: Nine adult macaques were used. Seven were injected intramuscularly with the VSVΔG/MARVGP-Musoke vaccine, and two recieved VSVΔG/ZEBOVGP as experimental controls (Daddario-DiCaprio et al., 2006).
  • Persistence: Not noted.
  • Immune Response: With the use of purified virus particles for an antigen source, immunoglobulin G (IgG) antibodies against MARV were detected through an enzyme-linked immunosorbent assay (ELISA). A transient and low-level recombinant VSV viremia was detected through virus isolation on the third day after vaccination in plasma from four of the VSVΔG/MARVGP-Musoke vaccinated animals. Both the MARV-Angola-challenged control animal and the MARV-Ravn-challenged control animal developed high titers in the blood, detected by plaque assay (Daddario-DiCaprio et al., 2006).
  • Side Effects: After either vaccination with VSVΔG/MARVGP-Musoke or after the MARV challenge, none of the animals showed any evidence of clinical illness (Daddario-DiCaprio et al., 2006).
  • Challenge Protocol: All animals were challenged with either MARV-Angola, MARV-Musoke, or MARV-Ravn 28 days after immunization (Daddario-DiCaprio et al., 2006).
  • Efficacy: VSVΔG/MARVGP-Musoke vector does protect nonhuman primates against a lethal challenge with both Ravn and Angola strains of MBGV. This approach seems almost as successful as the use of VEEV MARV GP and/or VEEV MARV NP, which protected NHP against a lethal homologous challenge, but did not protect against a lethal heterologous Ravn challenge (Daddario-DiCaprio et al., 2006).
References References References
Hevey et al., 1998: Hevey M, Negley D, Pushko P, Smith J, Schmaljohn A. Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates. Virology. 1998 Nov 10; 251(1); 28-37. [PubMed: 9813200 ].
Daddario-DiCaprio et al., 2006: Daddario-DiCaprio KM, Geisbert TW, Geisbert JB, Stroher U, Hensley LE, Grolla A, Fritz EA, Feldmann F, Feldmann H, Jones SM. Cross-protection against Marburg virus strains by using a live, attenuated recombinant vaccine. Journal of virology. 2006; 80(19); 9659-9666. [PubMed: 16973570].
Hevey et al., 1998: Hevey M, Negley D, Pushko P, Smith J, Schmaljohn A. Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates. Virology. 1998 Nov 10; 251(1); 28-37. [PubMed: 9813200 ].
Daddario-DiCaprio et al., 2006: Daddario-DiCaprio KM, Geisbert TW, Geisbert JB, Stroher U, Hensley LE, Grolla A, Fritz EA, Feldmann F, Feldmann H, Jones SM. Cross-protection against Marburg virus strains by using a live, attenuated recombinant vaccine. Journal of virology. 2006; 80(19); 9659-9666. [PubMed: 16973570].