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. 2019 Feb 8:4:8.
doi: 10.1038/s41541-019-0104-x. eCollection 2019.

A recombinant vesicular stomatitis-based Lassa fever vaccine elicits rapid and long-term protection from lethal Lassa virus infection in guinea pigs

Derek R Stein  1 , Bryce M Warner  1   2 , Geoff Soule  1 , Kevin Tierney  1 , Kathy L Frost  1 , Stephanie Booth  1 , David Safronetz  1   2
Affiliations

A recombinant vesicular stomatitis-based Lassa fever vaccine elicits rapid and long-term protection from lethal Lassa virus infection in guinea pigs

Derek R Stein et al. NPJ Vaccines. .

Abstract

The World Health Organization has identified Lassa virus (LASV) as one of the top five pathogens to cause a severe outbreak in the near future. This study assesses the ability of a leading vaccine candidate, recombinant Vesicular stomatitis virus expressing LASV glycoprotein (VSVΔG/LASVGPC), and its ability to induce rapid and long-term immunity to lethal guinea pig-adapted LASV (GPA-LASV). Outbred guinea pigs were vaccinated with a single dose of VSVΔG/LASVGPC followed by a lethal challenge of GPA-LASV at 7, 14, 25, 189, and 355 days post-vaccination. Statistically significant rapid and long-term protection was achieved at all time points with 100% protection at days 7 and 14 post-vaccination. While 83 and 87% protection were achieved at 25 days and 6 months post-vaccination, respectively. When guinea pigs were challenged one year after vaccination 71% protection was achieved. Notable infectious virus was isolated from the serum and tissues of some but not all animals. Total LASVGPC-specific IgG titers were also measured on a monthly basis leading up to LASV challenge however, it is unclear if antibody alone correlates with short and long term survival. These studies confirm that a single dose of VSVΔG/LASVGPC can induce rapid and long-term protection from LASV infection in an aggressive outbred model of infection, and supports further development in non-human primates.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Rapid protection from lethal Lassa virus challenge with a single dose of VSVΔG-LASVGPC vaccine. a Survival, weight loss (inset) and b temperature analysis of Hartley guinea pigs challenged 14 and 7 days post-vaccination (n = 6). c Survival, weight loss (inset) and d temperature analysis of Harley guinea pigs challenged 25 days post-vaccination (n = 6). Mantel-Cox survival analysis was used and all data are presented as mean values with error bars indicating SEM. p = 0.1234 (ns), 0.0332 (*), 0.0021 (**), 0.0002 (***), <0.0001 (****)
Fig. 2
Fig. 2
Viral burden and serological analysis of rapid vaccination with VSVΔG-LASVGPC. TCID50 analysis of serum, liver, lung and spleen collected from animals vaccinated a 7/14 DPV (2-Way Anova; Dunnett’s) and b 25 DPV (T-test; Holm-Sidak). Total LASVGPC-specific IgG titers were assessed by endpoint titration and the Log ECF90 for each time-point calculated for animals challenged c 7/14 DPV (One-Way Anova; Dunnett’s) and d 25 DPV (Two-tailed T-test), respectively. Data are presented as mean values with error bars indicating SEM. p = 0.1234 (ns), 0.0332 (*), 0.0021 (**), 0.0002 (***), <0.0001 (****)
Fig. 3
Fig. 3
Long-term protection from lethal Lassa virus challenge with a single dose of VSVΔG-LASVGPC vaccine. a Survival, weight loss (inset) and b temperature analysis of Hartley guinea pigs challenged 189 days post-vaccination (n = 8). c Survival, weight loss (inset) and d temperature analysis of Harley guinea pigs challenged 355 days post-vaccination (n = 8). Mantel-Cox survival analysis was used and data are presented as mean values with error bars indicating SEM. p = 0.1234 (ns), 0.0332 (*), 0.0021 (**), 0.0002 (***), <0.0001 (****)
Fig. 4
Fig. 4
Viral burden and serological analysis of long-term vaccination with VSVΔG-LASVGPC. TCID50 analysis of serum, liver, lung and spleen collected from animals vaccinated a 189 DPV and b 355 DPV (T-test; Holm-Sidak). Total LASVGPC-specific IgG titers were assessed by endpoint titration and the Log ECF90 for each time-point calculated for animals challenged c 189 DPV and d 355 DPV, respectively. Data are presented as mean values with error bars indicating SEM. p = 0.1234 (ns), 0.0332 (*), 0.0021 (**), 0.0002 (***), <0.0001 (****)
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