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Vaccine Detail

Heterologous MARV Protein VLP
Vaccine Information
  • Vaccine Name: Heterologous MARV Protein VLP
  • Target Pathogen: Marburg Virus
  • Target Disease: Hemorrhagic fever
  • Vaccine Ontology ID: VO_0004137
  • Type: Subunit vaccine
  • Antigen: MARV VP40 and GP were used (Swenson et al., 2005).
  • GP from Musoke Marburgvirus gene engineering:
    • Type: Recombinant protein preparation
    • 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.
  • 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.
  • Adjuvant:
  • Preparation: Expression plasmids were made through the use of MARV-Musoke strain. To produce the actual viral preparations, MARV-infected cell supernatents were clarified at 1500×g and then pelleted at 9500×g for 4 h in a Sorvall GSA rotor (Swenson et al., 2005).
  • Virulence: GP vaccination formed sufficient protection against homologous filovirus challenge, yet heterologous wild-type VLPs without GP failed to protect. Our data indicate that vaccination with GP was required and sufficient to form an immune response as heterologous wild-type VLPs or hybrid VLPs that did not contain the homologous GP failed. Vaccination with a mixture of EBOV and MARV VLPs was successful in forming an immune response (Swenson et al., 2005).

Host Response

Guinea pig Response

  • Host Strain: Strain 13
  • Vaccination Protocol: Strain 13 guinea pigs were vaccinated once with mVLPs, eVLPs, or an equal mixture of eVLPs and mVLPs in RIBI adjuvant, and the serum antibody levels against MARV and EBOV were measured (via ELISA) prior to challenge (Swenson et al., 2005).
    Control guinea pigs were vaccinated with RIBI adjuvant alone. Serum samples from the guinea pigs were
    obtained immediately before (PRE) or 28 days post-challenge (POST).Guinea pigs were vaccinated
  • Persistence: Not noted.
  • Immune Response: Animals vaccinated with the wild-type eVLP or e/m-VLPs did not have high serum antibody titers against MARV, but did have them against EBOV. Injection with mVLP and m/e-VLP vaccination resulted in high titers against MARV but not against EBOV. The vaccination containing EBOV GPin the form of eVLPor e/m-VLP resulted in antibodies against EBOV but not MARV. Finally, animals vaccinated with mVLP orm/e-VLP did not develop significant antibody titers against EBOV or MARV (Swenson et al., 2005).
  • Side Effects: None noted.
  • Challenge Protocol: Guinea pigs were challenged 28 days after a single vaccination with 1000 pfu of guinea pig-adapted MARV or EBOV (Swenson et al., 2005).
  • Efficacy: Guinea pigs challenged wuth VLPs containing homologous GP were protected from a lethal filovirus, and a eVLP or e/m-VLP vaccination yielded protection against EBOV infection. Vaccines containing heterologous proteins or homologous VP40 did not protect against lethal challenge (Swenson et al., 2005).
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 ].
Swenson et al., 2005: Swenson DL, Warfield KL, Negley DL, Schmaljohn A, Aman MJ, Bavari S. Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections. Vaccine. 2005; 23(23); 3033-3042. [PubMed: 15811650].