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Vaccine
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doi:10.1016/j.vaccine.2011.10.103 | How to Cite or Link Using DOI
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Cationic liposome?DNA complexes (CLDC) adjuvant enhances the immunogenicity and cross-protective efficacy of a pre-pandemic influenza A H5N1 vaccine in mice☆
Libo Donga, 1, Feng Liua, 1, Jeffery Fairmanb, David K. Hongc, David B. Lewisc, Thomas Monathd, John F. Warnerd, Jessica A. Belsera, Jenish Patela, Kathy Hancocka, Jacqueline M. Katza, Xiuhua Lua, Corresponding Author Contact Information, E-mail The Corresponding Author
a Centers for Disease Control and Prevention, Atlanta, GA, USA
b Colby Pharmaceutical Company, Menlo Park, CA, USA
c Department of Pediatrics, Interdepartmental Program in Immunology, and Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA
d Juvaris BioTherapeutics, Inc., Burlingame, CA, USA
Received 27 July 2011; revised 27 October 2011; Accepted 31 October 2011. Available online 12 November 2011.
Abstract
The development of pre-pandemic influenza A H5N1 vaccines that confer both antigen-sparing and cross-clade protection are a high priority given the limited worldwide capacity for influenza vaccine production, and the antigenic and genetic heterogeneity of circulating H5N1 viruses. The inclusion of potent adjuvants in vaccine formulations may achieve both of these aims. Here we show that the addition of JVRS-100, an adjuvant consisting of cationic liposome?DNA complexes (CLDC) to a clade 1-derived H5N1 split vaccine induced significantly higher virus-specific antibody than unadjuvanted formulations, with a >30-fold dose-sparing effect and induction of increased antigen-specific CD4+ T-cell responses in mice. All mice that received one dose of adjuvanted vaccine and subsequent H5N1 viral challenges exhibited mild illness, lower lung viral titers, undetectable spleen and brain viral titers, and 100% survival after either homologous clade 1 or heterologous clade 2 H5N1 viral challenges, whereas unadjuvanted vaccine recipients showed significantly increased weight loss, viral titers, and mortality. The protective immunity induced by JVRS-100 adjuvanted H5N1 vaccine was shown to last for over one year without significant waning. Thus, JVRS-100 adjuvanted H5N1 vaccine elicited enhanced humoral and T-cell responses, dose-sparing, and cross-clade protection in mice. CLDC holds promise as an adjuvant for human pre-pandemic inactivated H5N1 vaccines.
Highlights
► JVRS-100 adjuvant is comprised of novel cationic liposome?DNA complexes. ► JVRS-100 improved influenza H5N1 vaccine immunogenicity in mice. ► The addition of JVRS-100 to H5N1 vaccine resulted in significant antigen-sparing. ► JVRS-100 adjuvanted vaccine elicited Th1/IgG2a response and cross-protection. ► JVRS-100 adjuvanted H5N1 vaccine provided long-term protective immunity in mice.
http://www.sciencedirect.com/science/article/pii/S0264410X11017531
In Press, Uncorrected Proof - Note to users
doi:10.1016/j.vaccine.2011.10.103 | How to Cite or Link Using DOI
Permissions & Reprints
Cationic liposome?DNA complexes (CLDC) adjuvant enhances the immunogenicity and cross-protective efficacy of a pre-pandemic influenza A H5N1 vaccine in mice☆
Libo Donga, 1, Feng Liua, 1, Jeffery Fairmanb, David K. Hongc, David B. Lewisc, Thomas Monathd, John F. Warnerd, Jessica A. Belsera, Jenish Patela, Kathy Hancocka, Jacqueline M. Katza, Xiuhua Lua, Corresponding Author Contact Information, E-mail The Corresponding Author
a Centers for Disease Control and Prevention, Atlanta, GA, USA
b Colby Pharmaceutical Company, Menlo Park, CA, USA
c Department of Pediatrics, Interdepartmental Program in Immunology, and Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA
d Juvaris BioTherapeutics, Inc., Burlingame, CA, USA
Received 27 July 2011; revised 27 October 2011; Accepted 31 October 2011. Available online 12 November 2011.
Abstract
The development of pre-pandemic influenza A H5N1 vaccines that confer both antigen-sparing and cross-clade protection are a high priority given the limited worldwide capacity for influenza vaccine production, and the antigenic and genetic heterogeneity of circulating H5N1 viruses. The inclusion of potent adjuvants in vaccine formulations may achieve both of these aims. Here we show that the addition of JVRS-100, an adjuvant consisting of cationic liposome?DNA complexes (CLDC) to a clade 1-derived H5N1 split vaccine induced significantly higher virus-specific antibody than unadjuvanted formulations, with a >30-fold dose-sparing effect and induction of increased antigen-specific CD4+ T-cell responses in mice. All mice that received one dose of adjuvanted vaccine and subsequent H5N1 viral challenges exhibited mild illness, lower lung viral titers, undetectable spleen and brain viral titers, and 100% survival after either homologous clade 1 or heterologous clade 2 H5N1 viral challenges, whereas unadjuvanted vaccine recipients showed significantly increased weight loss, viral titers, and mortality. The protective immunity induced by JVRS-100 adjuvanted H5N1 vaccine was shown to last for over one year without significant waning. Thus, JVRS-100 adjuvanted H5N1 vaccine elicited enhanced humoral and T-cell responses, dose-sparing, and cross-clade protection in mice. CLDC holds promise as an adjuvant for human pre-pandemic inactivated H5N1 vaccines.
Highlights
► JVRS-100 adjuvant is comprised of novel cationic liposome?DNA complexes. ► JVRS-100 improved influenza H5N1 vaccine immunogenicity in mice. ► The addition of JVRS-100 to H5N1 vaccine resulted in significant antigen-sparing. ► JVRS-100 adjuvanted vaccine elicited Th1/IgG2a response and cross-protection. ► JVRS-100 adjuvanted H5N1 vaccine provided long-term protective immunity in mice.
http://www.sciencedirect.com/science/article/pii/S0264410X11017531