Journal article
Enhanced Influenza Virus-Like Particle Vaccination with a Structurally Optimized RIG-I Agonist as Adjuvant
Journal of virology, Vol.89(20), pp.10612-10624
01 Oct 2015
PMCID: PMC4580177
PMID: 26269188
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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'-triphosphate-containing RNA (5' pppRNA) RIG-I agonist (termed M8) were examined in combination with influenza virus-like particles (VLP) (M8-VLP) expressing H5N1 influenza virus 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 H5N1 influenza virus. M8-VLP immunization also led to long-term protective responses against influenza virus infection in mice. M8 adjuvantation of VLP increased endpoint and antibody titers and inhibited influenza virus replication in lungs compared with approved or experimental adjuvants alum, AddaVax, and poly(I.C). Uniquely, immunization with M8-VLP stimulated a T(H)1-biased CD4 T cell response, as determined by increased T(H)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 virus challenge.
IMPORTANCE
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 virus antibody titers and protected animals from lethal influenza virus 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.
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Details
- Title
- Enhanced Influenza Virus-Like Particle Vaccination with a Structurally Optimized RIG-I Agonist as Adjuvant
- Creators
- Vladimir Beljanski - Vaccine & Gene Therapy Institute of FloridaCindy Chiang - Vaccine & Gene Therapy Institute of FloridaGreg A. Kirchenbaum - Vaccine & Gene Therapy Institute of FloridaDavid Olagnier - Vaccine & Gene Therapy Institute of FloridaChalise E. Bloom - Vaccine & Gene Therapy Institute of FloridaTerianne Wong - Vaccine & Gene Therapy Institute of FloridaElias K. Haddad - Vaccine & Gene Therapy Institute of FloridaLydie Trautmann - Vaccine & Gene Therapy Institute of FloridaTed M. Ross - Vaccine & Gene Therapy Institute of FloridaJohn Hiscott - Vaccine & Gene Therapy Institute of Florida
- Publication Details
- Journal of virology, Vol.89(20), pp.10612-10624
- Publisher
- Amer Soc Microbiology
- Number of pages
- 13
- Grant note
- R56AI108861 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) AI108861 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Vaccine & Gene Therapy Institute of Florida
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Drexel University
- Identifiers
- 991020100074304721
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- Web of Science research areas
- Virology