Smith, TanyaO'Kennedy, Maretha MWandrag, Daniel BRAdeyemi, MAbolnik, C2019-10-282019-10-282019-07Smith, T. et al. 2019. Efficacy of a plant-produced virus-like particle vaccine in chickens challenged with Influenza a H6N2 virus. Plant Biotechnology Journal, pp. 111467-76441467-7652https://onlinelibrary.wiley.com/doi/full/10.1111/pbi.13219https://doi.org/10.1111/pbi.13219http://hdl.handle.net/10204/11192Copyright 2019 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The efficacy, safety, speed, scalability, and cost-effectiveness of producing hemagglutinin-based virus-like particle (VLP) vaccines in plants is well-established for human influenza, but untested for the massive poultry influenza vaccine market that remains dominated by traditional egg-grown oil-emulsion inactivated whole virus vaccines. For optimal efficacy, a vaccine should be closely antigenically matched to the field strain, requiring that influenza A vaccines be updated regularly. In this study, an H6 subtype VLP transiently expressed in Nicotiana benthamiana was formulated into a vaccine and evaluated for efficacy in chickens against challenge with a heterologous H6N2 virus. A single dose of the plant-produced H6 VLP vaccine elicited an immune response comparable to two doses of a commercial inactivated H6N2 vaccine, with mean hemagglutination inhibition titers of 9.3 log2 and 8.8 log2, respectively. Compared to the non-vaccinated control, the H6 VLP vaccine significantly reduced the proportion of shedders and the magnitude of viral shedding by >100-fold in the oropharynx and >6-fold in the cloaca, and shortened oropharyngeal viral shedding by at least a week. Despite its potency, the cost of the antigenic mismatch between the inactivated H6N2 vaccine and challenge strain was evident not only in this vaccine’s failure to reduce viral shedding compared to the non-vaccinated group, but its apparent exacerbation of oropharyngeal viral shedding until 21 days post challenge. We estimate that a kilogram of plant leaf material can produce H6 VLP vaccines sufficient for between 5,000 and 30,000 chickens, depending on the effective dose and whether one or two immunizations are administered.enNicotiana benthamianaH6N2VLP vaccineAvian influenzaChickensViral sheddingEfficacy of a plant-produced virus-like particle vaccine in chickens challenged with Influenza a H6N2 virusArticleSmith, T., O'Kennedy, M. M., Wandrag, D. B., Adeyemi, M., & Abolnik, C. (2019). Efficacy of a plant-produced virus-like particle vaccine in chickens challenged with Influenza a H6N2 virus. http://hdl.handle.net/10204/11192Smith, Tanya, Maretha M O'Kennedy, Daniel BR Wandrag, M Adeyemi, and C Abolnik "Efficacy of a plant-produced virus-like particle vaccine in chickens challenged with Influenza a H6N2 virus." (2019) http://hdl.handle.net/10204/11192Smith T, O'Kennedy MM, Wandrag DB, Adeyemi M, Abolnik C. Efficacy of a plant-produced virus-like particle vaccine in chickens challenged with Influenza a H6N2 virus. 2019; http://hdl.handle.net/10204/11192.TY - Article AU - Smith, Tanya AU - O'Kennedy, Maretha M AU - Wandrag, Daniel BR AU - Adeyemi, M AU - Abolnik, C AB - The efficacy, safety, speed, scalability, and cost-effectiveness of producing hemagglutinin-based virus-like particle (VLP) vaccines in plants is well-established for human influenza, but untested for the massive poultry influenza vaccine market that remains dominated by traditional egg-grown oil-emulsion inactivated whole virus vaccines. For optimal efficacy, a vaccine should be closely antigenically matched to the field strain, requiring that influenza A vaccines be updated regularly. In this study, an H6 subtype VLP transiently expressed in Nicotiana benthamiana was formulated into a vaccine and evaluated for efficacy in chickens against challenge with a heterologous H6N2 virus. A single dose of the plant-produced H6 VLP vaccine elicited an immune response comparable to two doses of a commercial inactivated H6N2 vaccine, with mean hemagglutination inhibition titers of 9.3 log2 and 8.8 log2, respectively. Compared to the non-vaccinated control, the H6 VLP vaccine significantly reduced the proportion of shedders and the magnitude of viral shedding by >100-fold in the oropharynx and >6-fold in the cloaca, and shortened oropharyngeal viral shedding by at least a week. Despite its potency, the cost of the antigenic mismatch between the inactivated H6N2 vaccine and challenge strain was evident not only in this vaccine’s failure to reduce viral shedding compared to the non-vaccinated group, but its apparent exacerbation of oropharyngeal viral shedding until 21 days post challenge. We estimate that a kilogram of plant leaf material can produce H6 VLP vaccines sufficient for between 5,000 and 30,000 chickens, depending on the effective dose and whether one or two immunizations are administered. DA - 2019-07 DB - ResearchSpace DP - CSIR KW - Nicotiana benthamiana KW - H6N2 KW - VLP vaccine KW - Avian influenza KW - Chickens KW - Viral shedding LK - https://researchspace.csir.co.za PY - 2019 SM - 1467-7644 SM - 1467-7652 T1 - Efficacy of a plant-produced virus-like particle vaccine in chickens challenged with Influenza a H6N2 virus TI - Efficacy of a plant-produced virus-like particle vaccine in chickens challenged with Influenza a H6N2 virus UR - http://hdl.handle.net/10204/11192 ER -