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A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses.

Safronetz D, Mire C, Rosenke K, Feldmann F, Haddock E, Geisbert T, Feldmann H - PLoS Negl Trop Dis (2015)

Bottom Line: Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans.Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever.Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.

ABSTRACT

Background: Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models.

Methodologies/principle findings: Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever.

Conclusions/significance: Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

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Related in: MedlinePlus

VSVΔG/LASVGPC protects strain 13 guinea pigs from infection following challenge with a highly divergent Nigerian Lassa virus isolate.Adult, inbred strain 13 guinea pigs were immunized with 1 x106 pfu of VSVΔG/LASVGPC (n = 8) or VSVΔG/ANDVGPC (n = 7) and challenged 28 days later with Lassa virus strain Pinneo. Animals were monitored for disease progression including weight loss for up to 45 days.
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pntd.0003736.g004: VSVΔG/LASVGPC protects strain 13 guinea pigs from infection following challenge with a highly divergent Nigerian Lassa virus isolate.Adult, inbred strain 13 guinea pigs were immunized with 1 x106 pfu of VSVΔG/LASVGPC (n = 8) or VSVΔG/ANDVGPC (n = 7) and challenged 28 days later with Lassa virus strain Pinneo. Animals were monitored for disease progression including weight loss for up to 45 days.

Mentions: In a final experiment, immunized guinea pigs were challenged with LASV Pinneo, a Nigerian LASV isolate which is among the most genetically divergent when compared to LASV Josiah [10]. Following infection, control (VSVΔG/ANDVGPC)-immunized animals demonstrated mild to moderate signs of disease, including lethargy and weight loss of between 5 and 10% of the starting body weight beginning around day 10 post-challenge. These signs of disease persisted until approximately day 22 at which point all animals recovered (Fig 4). In contrast, none of the animals immunized with VSVΔG/LV-GPC demonstrated any signs of disease throughout the course of the study. Supporting this, serological analysis conducted on convalescent serum samples revealed the presence of anti-LASV nucleocapsid IgG antibodies in the control group with titers between 1600 (n = 1) and ≥6400 (n = 6), while serological titers for VSVΔG/LASVGPC immunized animals were considerably lower ranging from equivocal (100, n = 5) to 400 (n = 3) (Table 1).


A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses.

Safronetz D, Mire C, Rosenke K, Feldmann F, Haddock E, Geisbert T, Feldmann H - PLoS Negl Trop Dis (2015)

VSVΔG/LASVGPC protects strain 13 guinea pigs from infection following challenge with a highly divergent Nigerian Lassa virus isolate.Adult, inbred strain 13 guinea pigs were immunized with 1 x106 pfu of VSVΔG/LASVGPC (n = 8) or VSVΔG/ANDVGPC (n = 7) and challenged 28 days later with Lassa virus strain Pinneo. Animals were monitored for disease progression including weight loss for up to 45 days.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401668&req=5

pntd.0003736.g004: VSVΔG/LASVGPC protects strain 13 guinea pigs from infection following challenge with a highly divergent Nigerian Lassa virus isolate.Adult, inbred strain 13 guinea pigs were immunized with 1 x106 pfu of VSVΔG/LASVGPC (n = 8) or VSVΔG/ANDVGPC (n = 7) and challenged 28 days later with Lassa virus strain Pinneo. Animals were monitored for disease progression including weight loss for up to 45 days.
Mentions: In a final experiment, immunized guinea pigs were challenged with LASV Pinneo, a Nigerian LASV isolate which is among the most genetically divergent when compared to LASV Josiah [10]. Following infection, control (VSVΔG/ANDVGPC)-immunized animals demonstrated mild to moderate signs of disease, including lethargy and weight loss of between 5 and 10% of the starting body weight beginning around day 10 post-challenge. These signs of disease persisted until approximately day 22 at which point all animals recovered (Fig 4). In contrast, none of the animals immunized with VSVΔG/LV-GPC demonstrated any signs of disease throughout the course of the study. Supporting this, serological analysis conducted on convalescent serum samples revealed the presence of anti-LASV nucleocapsid IgG antibodies in the control group with titers between 1600 (n = 1) and ≥6400 (n = 6), while serological titers for VSVΔG/LASVGPC immunized animals were considerably lower ranging from equivocal (100, n = 5) to 400 (n = 3) (Table 1).

Bottom Line: Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans.Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever.Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.

ABSTRACT

Background: Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models.

Methodologies/principle findings: Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever.

Conclusions/significance: Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

Show MeSH
Related in: MedlinePlus