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Vaccine Detail

VSV[Delta]G/LVGPC
Vaccine Information
  • Vaccine Name: VSV[Delta]G/LVGPC
  • Target Pathogen: Lassa Fever Virus
  • Target Disease: Lassa fever
  • Vaccine Ontology ID: VO_0004087
  • Type: Live Attenuated
  • LASVsSgp2 glycoprotein gene engineering:
    • Type: Protein
    • Description:
    • Detailed Gene Information: Click Here.
  • Preparation: The recombinant VSV expressing the glycoprotein of Lassa virus, strain Josiah, and Zaire ebolavirus (ZEBOV), strain Mayinga, were generated using the infectious clone for the VSV, Indiana serotype. Briefly, the appropriate open reading frames for the glycoproteins were generated by PCR, cloned into the VSV genomic vectors lacking the VSV glycoprotein gene, sequenced-confirmed, and rescued. The recombinant viruses expressing Lassa virus glycoprotein and ZEBOV glycoprotein were designated VSV[Delta]G/LVGPC (Figure 1A) and VSV[Delta]G/ZEBOVGP, respectively (Geisbert et al., 2005).
  • Virulence:
  • Description: VSV[Delta]G/LVGPC ia a live attenuated recombinant vesicular stomatitis virus expressing the GPC of Lassa virus, strain Josiah. Vaccines based on live attenuated rVSV have been highly effective in animal models and are particularly attractive because they can be administered by the mucosal route (Geisbert et al., 2005).
Host Response

Monkey Response

  • Host Strain: Cynomolgus macaques
  • Vaccination Protocol: Four cynomolgus macaques, 4–6 y old and weighing between 3 kg and 8 kg, were vaccinated intramuscularly with approximately 2 × 107 PFU of VSV[Delta]G/LVGPC, and two with an equivalent dose of VSV[Delta]G/ZEBOGP (controls). The six cynomolgus macaques were challenged intramuscularly 28 d after the single-dose immunization with 1 × 104 plaque-forming units of Lassa virus, Josiah strain (Geisbert et al., 2005).
  • Persistence: None noted
  • Side Effects: After vaccination, none of the nonhuman primates displayed any signs of clinical symptoms, indicating that the rVSVs were apathogenic for these animals (Geisbert et al., 2005).
  • Efficacy: The VSV-based vector expressing the Lassa virus GPC mediated complete protection of four of four cynomolgus monkeys from a high-dose lethal challenge of Lassa virus. Protection was associated with the generation of Lassa-specific CD8+ T cell and antibody responses. The primary concern regarding use of the rVSV vaccine platform in humans is related to the fact that this is a replication-competent vaccine, and thus demonstration of safety is of paramount importance (Geisbert et al., 2005).
  • Description: After the challenge, the two control animals started to show clinical signs of illness on day 3, when one of the animals had a fever. By day 10, both control animals developed macular rashes and anorexia, and one animal had severe facial edema, which is prognostic for a poor outcome in humans. These control animals succumbed to the Lassa virus challenge and were euthanized on day 11 and day 13. At necropsy, both controls showed lesions and pathological changes consistent with Lassa fever in nonhuman primates. In contrast, none of the vaccinated animals became sick, and all four animals were fully protected against the high Lassa challenge dose. By day 7 after challenge, all six monkeys were viremic. However by day 10, all four of the vaccinated animals had cleared the viremia, while both control animals had high viremias, which was maintained until euthanasia (Geisbert et al., 2005).
References
Geisbert et al., 2005: Geisbert TW, Jones S, Fritz EA, Shurtleff AC, Geisbert JB, Liebscher R, Grolla A, Stroher U, Fernando L, Daddario KM, Guttieri MC, Mothe BR, Larsen T, Hensley LE, Jahrling PB, Feldmann H. Development of a new vaccine for the prevention of Lassa fever. PLoS medicine. 2005 Jun; 2(6); e183. [PubMed: 15971954].