Cricket paralysis virus internal ribosome entry site-derived RNA promotes conventional vaccine efficacy by enhancing a balanced Th1/Th2 response

Autor: Hae Li Ko, Kyung Won Kang, Manki Song, Sang-Myeong Lee, Hye-Lim Park, Jae-Ouk Kim, Hye-Jung Kim, Jae-Hwan Nam, Eui-Cheol Shin, Hye Won Kwak, Seung Rok Ryu, Hyo Jung Park, Dae Gwin Jeong, Rhoon-Ho Kim, Min Ho Cha, Hun Kim
Rok vydání: 2019
Předmět:
CD4-Positive T-Lymphocytes
ELISPOT
enzyme-linked immunospot
dLN
draining lymph node
T-Lymphocytes
medicine.medical_treatment
Tfh
follicular helper T
CoV
coronavirus
CD8-Positive T-Lymphocytes
Antibodies
Viral
Mice
0302 clinical medicine
IRES
030212 general & internal medicine
Th1/Th2
Alum
Cells
Cultured
Adjuvant
Mice
Inbred BALB C
TNF
tumor necrosis factor
RIG-I
Chemotaxis
ELISA
enzyme-linked immunosorbent assay
Flow Cytometry
CrPV
Th2
T helper 2
NAbs
neutralizing antibodies
IGR
intergenic region
Infectious Diseases
Dicistroviridae
Molecular Medicine
Female
RIG
retinoic acid-inducible gene
DCs
dendritic cells
TLR
Toll-like receptor
PRNT
plaque-reduction neutralization test
HPV
030231 tropical medicine
Enzyme-Linked Immunosorbent Assay
HPV
human papillomavirus
Internal Ribosome Entry Sites
Biology
CrPV
Cricket paralysis virus
Article
03 medical and health sciences
Th2 Cells
Immune system
Adjuvants
Immunologic
MERS
Immunity
Tg
transgenic
medicine
Animals
Humans
IFN
interferon
ssRNAs
single-stranded RNAs
IRESs
internal ribosome entry sites
General Veterinary
General Immunology and Microbiology
fungi
MERS
Middle East respiratory syndrome
Public Health
Environmental and Occupational Health
RNA
TLR7
Th1 Cells
Vaccine efficacy
WT
wild-type
Virology
Immunity
Innate
IL
interleukin
Mice
Inbred C57BL
PFUs
plaque-forming units
APCs
Antigen presenting cells
hPBMCs
human peripheral blood mononuclear cells
VLP
virus-like particle
Myd88
myeloid differentiation primary response 88
Leukocytes
Mononuclear
Vaccine
Leukocyte chemotaxis
Zdroj: Vaccine
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2019.07.070
Popis: Highlights • RNA adjuvant was developed from the CrPV intergenic region IRES. • The RNA adjuvant functioned as an adjuvant with protein-based vaccines. • The RNA adjuvant increased vaccine efficacy and induced balanced Th1/Th2 response. • The RNA adjuvant enhanced APC chemotaxis.
An ideal adjuvant should increase vaccine efficacy through balanced Th1/Th2 responses and be safe to use. Recombinant protein-based vaccines are usually formulated with aluminum (alum)-based adjuvants to ensure an adequate immune response. However, use of alum triggers a Th2-biased immune induction, and hence is not optimal. Although the adjuvanticity of RNA has been reported, a systematic and overall investigation on its efficacy is lacking. We found that single strand RNA (termed RNA adjuvant) derived from cricket paralysis virus intergenic region internal ribosome entry site induced the expression of various adjuvant-function-related genes, such as type 1 and 2 interferon (IFN) and toll-like receptor (TLR), T cell activation, and leukocyte chemotaxis in human peripheral blood mononuclear cells; furthermore, its innate and IFN transcriptome profile patterns were similar to those of a live-attenuated yellow fever vaccine. This suggests that protein-based vaccines formulated using RNA adjuvant function as live-attenuated vaccines. Application of the RNA adjuvant in mouse enhanced the efficacy of Middle East respiratory syndrome spike protein, a protein-subunit vaccine and human papillomavirus L1 protein, a virus-like particle vaccine, by activating innate immune response through TLR7 and enhancing pAPC chemotaxis, leading to a balanced Th1/Th2 responses. Moreover, the combination of alum and the RNA adjuvant synergistically induced humoral and cellular immune responses and endowed long-term immunity. Therefore, RNA adjuvants have broad applicability and can be used with all conventional vaccines to improve vaccine efficacy qualitatively and quantitively.
Databáze: OpenAIRE
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