A vaccine based on recombinant modified Vaccinia Ankara containing the nucleoprotein from Lassa virus protects against disease progression in a guinea pig model

E. M. Kennedy; Stuart Dowall; Francisco Javier Salguero Bodes; P. Yeates; M. Aram; Roger Hewson

doi:10.1016/j.vaccine.2019.07.023

A vaccine based on recombinant modified Vaccinia Ankara containing the nucleoprotein from Lassa virus protects against disease progression in a guinea pig model

E. M. Kennedy^*, Stuart Dowall, Francisco Javier Salguero Bodes, P. Yeates, M. Aram, Roger Hewson

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Lassa fever remains the most imported viral haemorrhagic fever in Europe and is responsible for 5000 deaths per year throughout Western Africa. There is no vaccine and treatment is often ineffective. We have developed a vaccine based on modified Vaccinia Ankara expressing the nucleoprotein from Lassa virus (MVALassaNP). This study investigated the immunogenicity (in mice) and efficacy (in guinea pigs) of the MVALassaNP vaccine as a prime/boost or single vaccination regime. ELISA and ELISpot assays confirmed humoral and T-cell immunity following both a prime and prime/boost vaccination, with the prime/boost regime producing a statistically increased response compared to a prime only vaccine (P < 0.0001). The vaccine offered protection in guinea pigs against disease manifestations after challenge with virulent Lassa virus. Clinical signs, weight loss and temperature increases were observed in all animals receiving a control MVA vaccine, after challenge with Lassa virus. In contrast, no clinical signs, fever or weight loss were observed in any of the MVALassaNP vaccinated animals demonstrating that both a single immunisation, and prime/boost regime confer protection against disease progression. In conclusion, the MVALassaNP vaccine candidate elicits an immune response, demonstrates efficacy against Lassa virus disease and is suitable for further preclinical and clinical development.

Original language	English
Pages (from-to)	5404-5413
Number of pages	10
Journal	Vaccine
Volume	37
Issue number	36
DOIs	https://doi.org/10.1016/j.vaccine.2019.07.023
Publication status	Published - 23 Aug 2019

Bibliographical note

Funding Information:
The authors would like to thank the Biological Investigations Group and the Histology department (particularly Kirsty Emery for her involvement in the histology laboratory) at PHE Porton for their work during the project. This report is work commissioned by Innovate UK and the Department of Health and Social Care (Project title ?SRBI New Vaccines for Global Epidemics: LassaVacc; File Ref. 972223) and is funded through Official Development Assistance (ODA). The views expressed in this publication are those of the author(s) and not necessarily those of employing institutions or funding bodies.

Funding Information:
This report is work commissioned by Innovate UK and the Department of Health and Social Care (Project title “SRBI New Vaccines for Global Epidemics: LassaVacc; File Ref. 972223) and is funded through Official Development Assistance (ODA). The views expressed in this publication are those of the author(s) and not necessarily those of employing institutions or funding bodies.

Publisher Copyright:
© 2019

Keywords

Efficacy
Immunogenicity
Lassa
Modified Vaccinia Ankara (MVA)
Nucleoprotein
Recombinant vaccine
Vaccine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.vaccine.2019.07.023

Cite this

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title = "A vaccine based on recombinant modified Vaccinia Ankara containing the nucleoprotein from Lassa virus protects against disease progression in a guinea pig model",

abstract = "Lassa fever remains the most imported viral haemorrhagic fever in Europe and is responsible for 5000 deaths per year throughout Western Africa. There is no vaccine and treatment is often ineffective. We have developed a vaccine based on modified Vaccinia Ankara expressing the nucleoprotein from Lassa virus (MVALassaNP). This study investigated the immunogenicity (in mice) and efficacy (in guinea pigs) of the MVALassaNP vaccine as a prime/boost or single vaccination regime. ELISA and ELISpot assays confirmed humoral and T-cell immunity following both a prime and prime/boost vaccination, with the prime/boost regime producing a statistically increased response compared to a prime only vaccine (P < 0.0001). The vaccine offered protection in guinea pigs against disease manifestations after challenge with virulent Lassa virus. Clinical signs, weight loss and temperature increases were observed in all animals receiving a control MVA vaccine, after challenge with Lassa virus. In contrast, no clinical signs, fever or weight loss were observed in any of the MVALassaNP vaccinated animals demonstrating that both a single immunisation, and prime/boost regime confer protection against disease progression. In conclusion, the MVALassaNP vaccine candidate elicits an immune response, demonstrates efficacy against Lassa virus disease and is suitable for further preclinical and clinical development.",

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author = "Kennedy, {E. M.} and Stuart Dowall and {Salguero Bodes}, {Francisco Javier} and P. Yeates and M. Aram and Roger Hewson",

note = "Funding Information: The authors would like to thank the Biological Investigations Group and the Histology department (particularly Kirsty Emery for her involvement in the histology laboratory) at PHE Porton for their work during the project. This report is work commissioned by Innovate UK and the Department of Health and Social Care (Project title ?SRBI New Vaccines for Global Epidemics: LassaVacc; File Ref. 972223) and is funded through Official Development Assistance (ODA). The views expressed in this publication are those of the author(s) and not necessarily those of employing institutions or funding bodies. Funding Information: This report is work commissioned by Innovate UK and the Department of Health and Social Care (Project title “SRBI New Vaccines for Global Epidemics: LassaVacc; File Ref. 972223) and is funded through Official Development Assistance (ODA). The views expressed in this publication are those of the author(s) and not necessarily those of employing institutions or funding bodies. Publisher Copyright: {\textcopyright} 2019",

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AU - Yeates, P.

AU - Aram, M.

AU - Hewson, Roger

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N2 - Lassa fever remains the most imported viral haemorrhagic fever in Europe and is responsible for 5000 deaths per year throughout Western Africa. There is no vaccine and treatment is often ineffective. We have developed a vaccine based on modified Vaccinia Ankara expressing the nucleoprotein from Lassa virus (MVALassaNP). This study investigated the immunogenicity (in mice) and efficacy (in guinea pigs) of the MVALassaNP vaccine as a prime/boost or single vaccination regime. ELISA and ELISpot assays confirmed humoral and T-cell immunity following both a prime and prime/boost vaccination, with the prime/boost regime producing a statistically increased response compared to a prime only vaccine (P < 0.0001). The vaccine offered protection in guinea pigs against disease manifestations after challenge with virulent Lassa virus. Clinical signs, weight loss and temperature increases were observed in all animals receiving a control MVA vaccine, after challenge with Lassa virus. In contrast, no clinical signs, fever or weight loss were observed in any of the MVALassaNP vaccinated animals demonstrating that both a single immunisation, and prime/boost regime confer protection against disease progression. In conclusion, the MVALassaNP vaccine candidate elicits an immune response, demonstrates efficacy against Lassa virus disease and is suitable for further preclinical and clinical development.

AB - Lassa fever remains the most imported viral haemorrhagic fever in Europe and is responsible for 5000 deaths per year throughout Western Africa. There is no vaccine and treatment is often ineffective. We have developed a vaccine based on modified Vaccinia Ankara expressing the nucleoprotein from Lassa virus (MVALassaNP). This study investigated the immunogenicity (in mice) and efficacy (in guinea pigs) of the MVALassaNP vaccine as a prime/boost or single vaccination regime. ELISA and ELISpot assays confirmed humoral and T-cell immunity following both a prime and prime/boost vaccination, with the prime/boost regime producing a statistically increased response compared to a prime only vaccine (P < 0.0001). The vaccine offered protection in guinea pigs against disease manifestations after challenge with virulent Lassa virus. Clinical signs, weight loss and temperature increases were observed in all animals receiving a control MVA vaccine, after challenge with Lassa virus. In contrast, no clinical signs, fever or weight loss were observed in any of the MVALassaNP vaccinated animals demonstrating that both a single immunisation, and prime/boost regime confer protection against disease progression. In conclusion, the MVALassaNP vaccine candidate elicits an immune response, demonstrates efficacy against Lassa virus disease and is suitable for further preclinical and clinical development.

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A vaccine based on recombinant modified Vaccinia Ankara containing the nucleoprotein from Lassa virus protects against disease progression in a guinea pig model

Abstract

Bibliographical note

Keywords

UN SDGs

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