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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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VSVΔG/LASVGPC protects strain 13 guinea pigs from infection / disease following challenge with a Malian Lassa virus isolate.Adult, inbred strain 13 guinea pigs were immunized with 1 x106 pfu of VSVΔG/LASVGPC (n = 9) or VSVΔG/ANDVGPC (n = 9) and challenged 28 days later with Lassa virus strain Soromba-R. Animals were monitored for disease progression including weight loss for up to 45 days. * p = 0.001.
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pntd.0003736.g003: VSVΔG/LASVGPC protects strain 13 guinea pigs from infection / disease following challenge with a Malian Lassa virus isolate.Adult, inbred strain 13 guinea pigs were immunized with 1 x106 pfu of VSVΔG/LASVGPC (n = 9) or VSVΔG/ANDVGPC (n = 9) and challenged 28 days later with Lassa virus strain Soromba-R. Animals were monitored for disease progression including weight loss for up to 45 days. * p = 0.001.

Mentions: Similar to the results of the homologous challenge experiment outlined above, VSVΔG/LASVGPC completely protected guinea pigs against challenge with non-homologous LASV isolates originating from geographically distinct regions of West Africa (Fig 2). As previously observed, LASV Z-132 was 100% lethal within 18 days post-inoculation in control (VSVΔG/ANDVGPC)-immunized strain 13 guinea pigs [32]. In contrast, animals immunized with VSVΔG/LASVGPC were 100% protected against the Liberian LASV with no signs of disease observed throughout the course of the experiment (p = 0.0022). Furthermore, infectious virus could not be isolated from tissue samples collected from representative animals euthanized and sampled during the terminal phase of disease in the experimental group (Fig 2, inset). Similarly, animals immunized with VSVΔG/LASVGPC completely resisted challenge with the Malian LASV isolate and although (as previously described) Soromba-R is not 100% lethal in naïve animals [32], there was a statistically significant increase in the survival rate associated with VSVΔG/LASVGPC immunization (p = 0.001) (Fig 3)


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 / disease following challenge with a Malian Lassa virus isolate.Adult, inbred strain 13 guinea pigs were immunized with 1 x106 pfu of VSVΔG/LASVGPC (n = 9) or VSVΔG/ANDVGPC (n = 9) and challenged 28 days later with Lassa virus strain Soromba-R. Animals were monitored for disease progression including weight loss for up to 45 days. * p = 0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003736.g003: VSVΔG/LASVGPC protects strain 13 guinea pigs from infection / disease following challenge with a Malian Lassa virus isolate.Adult, inbred strain 13 guinea pigs were immunized with 1 x106 pfu of VSVΔG/LASVGPC (n = 9) or VSVΔG/ANDVGPC (n = 9) and challenged 28 days later with Lassa virus strain Soromba-R. Animals were monitored for disease progression including weight loss for up to 45 days. * p = 0.001.
Mentions: Similar to the results of the homologous challenge experiment outlined above, VSVΔG/LASVGPC completely protected guinea pigs against challenge with non-homologous LASV isolates originating from geographically distinct regions of West Africa (Fig 2). As previously observed, LASV Z-132 was 100% lethal within 18 days post-inoculation in control (VSVΔG/ANDVGPC)-immunized strain 13 guinea pigs [32]. In contrast, animals immunized with VSVΔG/LASVGPC were 100% protected against the Liberian LASV with no signs of disease observed throughout the course of the experiment (p = 0.0022). Furthermore, infectious virus could not be isolated from tissue samples collected from representative animals euthanized and sampled during the terminal phase of disease in the experimental group (Fig 2, inset). Similarly, animals immunized with VSVΔG/LASVGPC completely resisted challenge with the Malian LASV isolate and although (as previously described) Soromba-R is not 100% lethal in naïve animals [32], there was a statistically significant increase in the survival rate associated with VSVΔG/LASVGPC immunization (p = 0.001) (Fig 3)

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