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 (Pâ¯<â¯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.
Subject(s)
Lassa virus/immunology , Nucleoproteins/immunology , Vaccinia/immunology , Vaccinia/prevention & control , Animals , Cell Line , Cricetinae , Enzyme-Linked Immunosorbent Assay , Female , Guinea Pigs , Vaccination , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Vaccinia virus/immunology , Vaccinia virus/pathogenicityABSTRACT
Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15-70% of reported cases are fatal with no approved vaccine available. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus nucleoprotein. Cellular and humoral immunogenicity was confirmed in 2 mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. Despite the immune responses generated post-immunisation, the vaccine failed to protect animals from lethal disease in a challenge model.
Subject(s)
Antibodies, Viral/blood , Hemorrhagic Fever Virus, Crimean-Congo/immunology , Hemorrhagic Fever, Crimean/prevention & control , Immunogenicity, Vaccine/immunology , Nucleoproteins/immunology , Vaccines, Synthetic/immunology , Viral Proteins/immunology , Viral Vaccines/immunology , Animals , Antibodies, Viral/immunology , Cell Line , Chick Embryo , Chlorocebus aethiops , Cricetinae , Hemorrhagic Fever, Crimean/immunology , Humans , Immunization , Mice , Mice, Knockout , Receptor, Interferon alpha-beta/genetics , Vero Cells , Viral Load/immunologyABSTRACT
Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab) has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity against Ebola virus.
Subject(s)
Antibodies, Viral/immunology , Ebolavirus/immunology , Phosphatidylserines/immunology , Virion/immunology , Animals , Antibodies, Viral/metabolism , Cell Line , Cells, Cultured , Chlorocebus aethiops , Ebolavirus/metabolism , Flow Cytometry , Fluorescent Antibody Technique , Hemorrhagic Fever, Ebola/immunology , Hemorrhagic Fever, Ebola/virology , Humans , Phosphatidylserines/metabolism , Protein Binding/immunology , Vero Cells , Virion/metabolismABSTRACT
Recombinant nucleoprotein from Crimean-Congo Haemorrhagic Fever (CCHF) virus was successfully derived from a baculovirus expression system and purified for use in a novel enzyme-linked immunosorbent assay (ELISA) diagnostic test. Comparable tests were used for detection of IgG and IgM antibodies, thus allowing efficient detection of both antibodies in parallel. The major benefits of the assay also included removing any requirement for polyclonal sera, thus eliminating variation in preparations and allowing standardisation between laboratories. The assay was successfully tested using a panel of positive sera supplied from samples identified as being positive in Turkey, Tajikistan and Kosovo and shown to be sensitive and specific. It is envisaged that this simple diagnostic ELISA for CCHF virus infection which removes the reliance on polyclonal antibody preparations, will be accessible to a wider range of laboratories enabling them to carry out routine diagnosis. This will improve the efficiency of diagnosis and subsequent management of infected patients.
