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. 2005 Jun;2(6):e183.
doi: 10.1371/journal.pmed.0020183. Epub 2005 Jun 28.

Development of a new vaccine for the prevention of Lassa fever

Thomas W Geisbert  1 , Steven Jones, Elizabeth A Fritz, Amy C Shurtleff, Joan B Geisbert, Ryan Liebscher, Allen Grolla, Ute Ströher, Lisa Fernando, Kathleen M Daddario, Mary C Guttieri, Bianca R Mothé, Tom Larsen, Lisa E Hensley, Peter B Jahrling, Heinz Feldmann
Affiliations

Development of a new vaccine for the prevention of Lassa fever

Thomas W Geisbert et al. PLoS Med. 2005 Jun.

Abstract

Background: Recent importation of Lassa fever into Germany, the Netherlands, the United Kingdom, and the United States by travelers on commercial airlines from Africa underscores the public health challenge of emerging viruses. Currently, there are no licensed vaccines for Lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge.

Methods and findings: We developed a replication-competent vaccine against Lassa virus based on attenuated recombinant vesicular stomatitis virus vectors expressing the Lassa viral glycoprotein. A single intramuscular vaccination of the Lassa vaccine elicited a protective immune response in nonhuman primates against a lethal Lassa virus challenge. Vaccine shedding was not detected in the monkeys, and none of the animals developed fever or other symptoms of illness associated with vaccination. The Lassa vaccine induced strong humoral and cellular immune responses in the four vaccinated and challenged monkeys. Despite a transient Lassa viremia in vaccinated animals 7 d after challenge, the vaccinated animals showed no evidence of clinical disease. In contrast, the two control animals developed severe symptoms including rashes, facial edema, and elevated liver enzymes, and ultimately succumbed to the Lassa infection.

Conclusion: Our data suggest that the Lassa vaccine candidate based on recombinant vesicular stomatitis virus is safe and highly efficacious in a relevant animal model that faithfully reproduces human disease.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Lassa Virus Vaccine Design and Vaccination Regimen
(A) Left, schematic diagram of the recombinant VSV expressing the glycoprotein of Lassa virus. The VSV glycoprotein (G) was replaced with the Lassa virus glycoprotein (LV GPC). Shown are the nucleocapsid (N), phosphoprotein (P), matrix (M), and RNA-dependent RNA polymerase (L). Right, gold sphere labeling (10-nm spheres) of VSVΔG/LVGPC particles by immunoelectron microscopy using a pool of two murine monoclonal antibodies directed against Lassa virus GP1 and GP2; particles were negatively contrasted with 1% uranyl acetate. (B) Time line for vaccination and Lassa viral challenge study. Vaccination of cynomolgus monkeys was done with a single intramuscular dose of 10 7 PFU of either VSVΔG/LVGPC (four animals) or VSVΔG/ZEBOVGP (two animals). Challenge was performed with a single intramuscular dose of 104 PFU of Lassa virus, strain Josiah. Arrows indicate day of sampling (blood and swabs).
Figure 2
Figure 2. Hepatic Enzyme Levels in Sera of Cynomolgus Monkeys After Challenge with Lassa Virus
Results of ALT (A) and AST (B) assays are shown for the four VSVΔG/LVGPC-vaccinated macaques (closed symbols) and the two control monkeys (open symbols).
Figure 3
Figure 3. Viremia in Nonhuman Primates after Vaccination and Lassa Virus Challenge
Viremia levels after vaccination (A) and Lassa virus challenge (B) were determined in plasma taken at the indicated times after vaccination and Lassa virus challenge (see Figure 1B). RNA was isolated from plasma, and PCR specific for VSV and Lassa virus were performed as described in Methods. Note: Subjects 1–4 were vaccinated with VSVΔG/LVGPC, while controls 1 and 2 were vaccinated with VSVΔG/ZEBOVGP.
Figure 4
Figure 4. Humoral Immune Response in Nonhuman Primates to Lassa Virus before and after Lassa Challenge
(A) IgG responses were measured using an established ELISA (see Methods). The titers are presented as endpoint dilutions. (B) Neutralizing antibodies were detected by a plaque reduction neutralization assay as described in Methods. Titers are presented as endpoint dilutions. Note: Subjects 1–4 were vaccinated with VSVΔG/LVGPC, while controls 1 and 2 were vaccinated with VSVΔG/ZEBOVGP.
Figure 5
Figure 5. Cellular Immune Response (IFN-γ) in Nonhuman Primates before Vaccination, after Vaccination, and after Lassa Virus Challenge
Intracellular levels of IFN-γ were determined in CD4- and CD8-positive T-cell populations before vaccination (−28), after vaccination (−14 and 0), and after challenge with Lassa virus (7, 14, and 30); challenge was administered on day 0. Strong cellular responses following restimulation with transformed cells expressing Lassa GPC were seen in three of the four animals after challenge. Note: Subjects 1–4 were vaccinated with VSVΔG/LVGPC, while controls 1 and 2 were vaccinated with VSVΔG/ZEBOVGP.
Figure 6
Figure 6. Cellular Immune Response (TNF-α) in Nonhuman Primates before Vaccination, after Vaccination, and after Lassa Virus Challenge
Intracellular levels of TNF-α were determined in CD4- and CD8-positive T-cell populations before vaccination (−28), after vaccination (−14 and 0), and after challenge with Lassa virus (7, 14, and 30); challenge was administered on day 0. Strong cellular responses following restimulation with transformed cells expressing Lassa GPC were seen in three of the four animals after challenge. Note: Subjects 1–4 were vaccinated with VSVΔG/LVGPC, while controls 1 and 2 were vaccinated with VSVΔG/ZEBOVGP.
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References

    1. Fisher-Hoch SP, McCormick JB. Lassa fever vaccine: A review. Expert Rev Vaccines. 2004;3:103–111. - PubMed
    1. McCormick JB, Webb PA, Krebs JW, Johnson KM, Smith ES. A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis. 1987;155:437–444. - PubMed
    1. Fisher-Hoch SP, Tomori O, Nasidi A, Perez-Oronoz GI, Fakile Y, et al. Review of cases of nosocomial Lassa fever in Nigeria: The high price of poor medical practice. Br Med J. 1995;311:857–859. - PMC - PubMed
    1. Communicable Disease Surveillance Centre. Lassa fever imported to England. Commun Dis Rep CDR Weekly. 2000;10:99. - PubMed
    1. Schmitz H, Kohler B, Laue T, Drosten C, Veldkamp PJ, et al. Monitoring of clinical and laboratory data in two cases of imported Lassa fever. Microbes Infect. 2002;4:43–50. - PubMed

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