tetano
Editor, Senior Moderator
J Virol. 2015 Aug 12. pii: JVI.01526-15. [Epub ahead of print]
[h=1]Enhanced influenza VLP vaccination with a structurally optimized RIG-I agonist as adjuvant.[/h] Beljanski V[SUP]1[/SUP], Chiang C[SUP]1[/SUP], Kirchenbaum GA[SUP]1[/SUP], Olagnier D[SUP]1[/SUP], Bloom CE[SUP]1[/SUP], Wong T[SUP]1[/SUP], Haddad EK[SUP]1[/SUP], Trautmann L[SUP]1[/SUP], Ross TM[SUP]1[/SUP], Hiscott J[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The molecular interaction between viral RNA and the cytosolic sensor RIG-I represents the initial trigger in the development of an effective immune response against infection with RNA viruses, resulting in innate immune activation and subsequent induction of adaptive responses. In the present study, the adjuvant properties of a sequence-optimized 5' pppRNA RIG-I agonist (termed M8) were examined in combination with influenza virus-like particles (VLP) expressing influenza H5N1 hemagglutinin (HA) and neuraminidase (NA) as immunogens. In combination with VLP, M8 increased the antibody response to VLP immunization, provided VLP antigen sparing, and protected mice from a lethal challenge with influenza H5N1.. M8-VLP immunization also led to long term protective responses against influenza infection in mice. M8 adjuvantation of VLP increased endpoint and antibody titers and inhibited influenza replication in lungs when compared with approved or experimental adjuvants Alum, AddaVax, and poly(I:C). Uniquely, immunization with M8-VLP stimulated a T[SUB]H[/SUB]1-biased CD4 T cell response, as determined by increased T[SUB]H[/SUB]1 cytokine levels in CD4 T cells and increased IgG2 levels in sera. Collectively, these data demonstrate that a sequence-optimized, RIG-I specific agonist is a potent adjuvant that can be utilized to increase the efficacy of influenza VLP vaccination and dramatically improve humoral and cellular mediated protective responses against influenza challenge.
[h=4]IMPORTANCE:[/h] The development of novel adjuvants to increase vaccine immunogenicity is an important goal that seeks to improve vaccine efficacy and ultimately prevent infections that endanger human health. This proof-of-principle study investigated the adjuvant properties of a sequence-optimized 5' pppRNA agonist (M8) with enhanced capacity to stimulate antiviral and inflammatory gene networks using influenza virus-like particles (VLP) expressing HA and NA as immunogens. Vaccination with VLP in combination with M8 increased anti-influenza antibody titers and protected animals from the lethal influenza challenge, highlighting the potential clinical use of M8 as an adjuvant in vaccine development. Altogether, the results describe a novel immunostimulatory agonist targeted to the cytosolic RIG-I sensor as an attractive vaccine adjuvant candidate that can be used to increase vaccine efficacy, a pressing issue in children and the elderly population.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26269188 [PubMed - as supplied by publisher]
[h=1]Enhanced influenza VLP vaccination with a structurally optimized RIG-I agonist as adjuvant.[/h] Beljanski V[SUP]1[/SUP], Chiang C[SUP]1[/SUP], Kirchenbaum GA[SUP]1[/SUP], Olagnier D[SUP]1[/SUP], Bloom CE[SUP]1[/SUP], Wong T[SUP]1[/SUP], Haddad EK[SUP]1[/SUP], Trautmann L[SUP]1[/SUP], Ross TM[SUP]1[/SUP], Hiscott J[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The molecular interaction between viral RNA and the cytosolic sensor RIG-I represents the initial trigger in the development of an effective immune response against infection with RNA viruses, resulting in innate immune activation and subsequent induction of adaptive responses. In the present study, the adjuvant properties of a sequence-optimized 5' pppRNA RIG-I agonist (termed M8) were examined in combination with influenza virus-like particles (VLP) expressing influenza H5N1 hemagglutinin (HA) and neuraminidase (NA) as immunogens. In combination with VLP, M8 increased the antibody response to VLP immunization, provided VLP antigen sparing, and protected mice from a lethal challenge with influenza H5N1.. M8-VLP immunization also led to long term protective responses against influenza infection in mice. M8 adjuvantation of VLP increased endpoint and antibody titers and inhibited influenza replication in lungs when compared with approved or experimental adjuvants Alum, AddaVax, and poly(I:C). Uniquely, immunization with M8-VLP stimulated a T[SUB]H[/SUB]1-biased CD4 T cell response, as determined by increased T[SUB]H[/SUB]1 cytokine levels in CD4 T cells and increased IgG2 levels in sera. Collectively, these data demonstrate that a sequence-optimized, RIG-I specific agonist is a potent adjuvant that can be utilized to increase the efficacy of influenza VLP vaccination and dramatically improve humoral and cellular mediated protective responses against influenza challenge.
[h=4]IMPORTANCE:[/h] The development of novel adjuvants to increase vaccine immunogenicity is an important goal that seeks to improve vaccine efficacy and ultimately prevent infections that endanger human health. This proof-of-principle study investigated the adjuvant properties of a sequence-optimized 5' pppRNA agonist (M8) with enhanced capacity to stimulate antiviral and inflammatory gene networks using influenza virus-like particles (VLP) expressing HA and NA as immunogens. Vaccination with VLP in combination with M8 increased anti-influenza antibody titers and protected animals from the lethal influenza challenge, highlighting the potential clinical use of M8 as an adjuvant in vaccine development. Altogether, the results describe a novel immunostimulatory agonist targeted to the cytosolic RIG-I sensor as an attractive vaccine adjuvant candidate that can be used to increase vaccine efficacy, a pressing issue in children and the elderly population.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26269188 [PubMed - as supplied by publisher]