Title | The efficacy of current vaccines and novel Nanobody-based antivirals against highly pathogenic rabies and lyssaviruses |
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Authors | Wright, E., Hultberg, A., Rosseels, V., Vaughan, A., Saunders, M., Koenders, M., Verrips, T., Fooks, A.R., van Gucht, S., Weiss, R.A., de Haard, H.J. and Vanlandschoot, P. |
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Type | Conference paper |
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Abstract | Current rabies virus (RABV; lyssavirus genotype 1) vaccines and RABV immunoglobulins (RIG) confer a robust protective immunity against genotype 1 isolates. However, they offer partial or no protection against non-genotype 1 lyssaviruses and the high costs of such treatments, especially RIG, can result in poor availability/coverage. Therefore, alternative intervention strategies are required to address these issues. Using a pseudotype-based neutralisation assay we first evaluated the efficacy of commercial RABV vaccines against each lyssavirus genotype. Existing RABV vaccines stimulate high neutralising serum antibody titres against RABV isolates but do not confer protection against antigenically divergent lyssaviruses. Subsequently, a selection of anti-rabies llama (Llama glama) heavy chain antibody fragments (VHH/Nanobody®) was undertaken from immune libraries and tested for neutralising potency against a panel of geographically divergent RABV isolates and a range of lyssaviruses using live virus (RFFIT) and pseudotype neutralisation assays. Studies using the selected VHH reveal strong neutralising potencies against all RABV isolates and the majority of lyssavirus genotypes tested (in the nanomolar range). Bivalent constructs, made by fusion of identical or different VHH, greatly improved neutralising potency. Improved biologicals are required to counter the public health threat posed by these highly pathogenic viruses and llama VHH offer an attractive alternative. |
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Year | 2010 |
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Conference | Society For General Microbiology Spring 2010 Meeting |
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Publication dates |
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Published | 2010 |
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