tetano
Editor, Senior Moderator
J Virol. 2010 Oct 13. [Epub ahead of print]
Cationic Lipid/DNA Complex-Adjuvanted Influenza A Vaccination Induces Robust Cross-Protective Immunity.
Hong DK, Chang S, Botham CM, Giffon TD, Fairman J, Lewis DB.
Department of Pediatrics, Interdepartmental Program in Immunology, and Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California 94305; and Juvaris BioTherapeutics, Inc., Burlingame, California 94010.
Abstract
Influenza A is a negative strand segmented RNA virus in which antigenically distinct viral subtypes are defined by the hemagglutinin (HA) and neuraminidase (NA) major viral surface proteins. An ideal inactivated vaccine for influenza A would not only induce highly robust strain-specific humoral and T-cell immune responses, but also cross-protective immunity, in which an immune response to antigens from a particular viral subtype, e.g., H3N2, would protect against other viral subtypes, e.g., H1N1. Cross-protective immunity would help limit outbreaks from newly emerging antigenically novel strains. Here, we show in mice that the addition of cationic lipid/non-coding DNA complexes (CLDC) adjuvant to whole inactivated influenza A vaccine induces significantly more robust adaptive immune responses both in quantity and quality than aluminum hydroxide (alum), which is currently the most widely used adjuvant in clinical human vaccination. CLDC-adjuvanted vaccine induced higher total influenza-specific IgG, particularly for the IgG2a/c subclass. Higher levels of multi-cytokine-producing influenza-specific CD4 and CD8 T cells were induced by CLDC-adjuvanted compared with alum-adjuvanted vaccine. Importantly, CLDC-adjuvanted vaccine provided significant cross-protection from either a sublethal or lethal influenza A viral challenge with a different subtype than that used for vaccination. This superior cross-protection afforded by the CLDC adjuvant required CD8 T-cell recognition of viral peptides presented by classical major histocompatibility complex class I proteins. Together, these results suggest that CLDC has particular promise for vaccine strategies in which T cells play an important role, and may offer new opportunities for more effective control of human influenza epidemics and pandemics by inactivated vaccination.
PMID: 20943978 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20943978
Cationic Lipid/DNA Complex-Adjuvanted Influenza A Vaccination Induces Robust Cross-Protective Immunity.
Hong DK, Chang S, Botham CM, Giffon TD, Fairman J, Lewis DB.
Department of Pediatrics, Interdepartmental Program in Immunology, and Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California 94305; and Juvaris BioTherapeutics, Inc., Burlingame, California 94010.
Abstract
Influenza A is a negative strand segmented RNA virus in which antigenically distinct viral subtypes are defined by the hemagglutinin (HA) and neuraminidase (NA) major viral surface proteins. An ideal inactivated vaccine for influenza A would not only induce highly robust strain-specific humoral and T-cell immune responses, but also cross-protective immunity, in which an immune response to antigens from a particular viral subtype, e.g., H3N2, would protect against other viral subtypes, e.g., H1N1. Cross-protective immunity would help limit outbreaks from newly emerging antigenically novel strains. Here, we show in mice that the addition of cationic lipid/non-coding DNA complexes (CLDC) adjuvant to whole inactivated influenza A vaccine induces significantly more robust adaptive immune responses both in quantity and quality than aluminum hydroxide (alum), which is currently the most widely used adjuvant in clinical human vaccination. CLDC-adjuvanted vaccine induced higher total influenza-specific IgG, particularly for the IgG2a/c subclass. Higher levels of multi-cytokine-producing influenza-specific CD4 and CD8 T cells were induced by CLDC-adjuvanted compared with alum-adjuvanted vaccine. Importantly, CLDC-adjuvanted vaccine provided significant cross-protection from either a sublethal or lethal influenza A viral challenge with a different subtype than that used for vaccination. This superior cross-protection afforded by the CLDC adjuvant required CD8 T-cell recognition of viral peptides presented by classical major histocompatibility complex class I proteins. Together, these results suggest that CLDC has particular promise for vaccine strategies in which T cells play an important role, and may offer new opportunities for more effective control of human influenza epidemics and pandemics by inactivated vaccination.
PMID: 20943978 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20943978