tetano
Editor, Senior Moderator
Hum Vaccin Immunother. 2013 Dec 30;10(3). [Epub ahead of print]
Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge.
Mallajosyula JK1, Hiatt E2, Hume S2, Johnson A2, Jeevan T3, Chikwamba R4, Pogue GP5, Bratcher B2, Haydon H2, Webby RJ3, McCormick AA1.
Author information
Abstract
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 15?g 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 a 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 otherwise low potency HA subunit protein.
KEYWORDS:
H1N1, HA subunit protein, Influenza, dose sparing, nanoparticle, plant made pharmaceuticals, vaccination
PMID:
24378714
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24378714
Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge.
Mallajosyula JK1, Hiatt E2, Hume S2, Johnson A2, Jeevan T3, Chikwamba R4, Pogue GP5, Bratcher B2, Haydon H2, Webby RJ3, McCormick AA1.
Author information
Abstract
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 15?g 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 a 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 otherwise low potency HA subunit protein.
KEYWORDS:
H1N1, HA subunit protein, Influenza, dose sparing, nanoparticle, plant made pharmaceuticals, vaccination
PMID:
24378714
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24378714