Mallajosyula, JKHiatt, EHume, SJohnson, AJeevan, TChikwamba, Rachel KPogue, GPBratcherHaydon, HWebby, RJMcCormick, AA2015-05-252015-05-252014-03Mallajosyula, JK, Hiatt, E, Hume, S, Johnson, A, Jeevan, T, Chikwamba, R, Pogue GP, Bratcher, B, Haydon, H, Webby, RJ and McCormick, AA. 2014. Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge. Journal of Human Vaccines & Immunotherapeutics, vol. 10(3), pp 586-5952164-5515http://hdl.handle.net/10204/7977Copyright: 2014 Taylor & Francis. This is the pre-print/post-print version of the work. The definitive version is published in the Journal of Human Vaccines & Immunotherapeutics, vol. 10(3), pp 586-595. Due to copyright restrictions, the attached PDF file only contains the abstract of the full text item. For access to the full text item, please consult the publisher's websiteRecombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein.enInfluenzaH1N1 vaccinePlant made pharmaceuticalsHA subunit proteinVaccinationNanoparticlesDose sparingArticleMallajosyula, J., Hiatt, E., Hume, S., Johnson, A., Jeevan, T., Chikwamba, R. K., ... McCormick, A. (2014). Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge. http://hdl.handle.net/10204/7977Mallajosyula, JK, E Hiatt, S Hume, A Johnson, T Jeevan, Rachel K Chikwamba, GP Pogue, et al "Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge." (2014) http://hdl.handle.net/10204/7977Mallajosyula J, Hiatt E, Hume S, Johnson A, Jeevan T, Chikwamba RK, et al. Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge. 2014; http://hdl.handle.net/10204/7977.TY - Article AU - Mallajosyula, JK AU - Hiatt, E AU - Hume, S AU - Johnson, A AU - Jeevan, T AU - Chikwamba, Rachel K AU - Pogue, GP AU - Bratcher AU - Haydon, H AU - Webby, RJ AU - McCormick, AA AB - Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein. DA - 2014-03 DB - ResearchSpace DP - CSIR KW - Influenza KW - H1N1 vaccine KW - Plant made pharmaceuticals KW - HA subunit protein KW - Vaccination KW - Nanoparticles KW - Dose sparing LK - https://researchspace.csir.co.za PY - 2014 SM - 2164-5515 T1 - Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge TI - Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge UR - http://hdl.handle.net/10204/7977 ER -