Immunomodulatory Effects of dsRNA and Its Potential as Vaccine Adjuvant

Abstract

dsRNA can be detected by pattern recognition receptors, for example, TLR3, MDA-5, NLRP3 to induce proinflammatory cytokines responsible for innate/adaptive immunity. Recognized by endosomal TLR3 in myeloid DCs (mDCs), dsRNA can activate mDCs into mature antigen presenting cells (mAPCs) which in turn present antigen epitopes with MHC-I molecules to naïve T cells. Coadministration of protein and synthetic dsRNA analogues can elicit an antigen-specific Th1-polarized immune response which stimulates the CD8+ CTL response and possibly dampen Th17 response. Synthetic dsRNA analogues have been tested as vaccine adjuvant against viral infections in animal models. However, a dsRNA receptor, TLR3 can be expressed in tumor cells while other members of TLR family, for example, TLR4 and TLR2 have been shown to promote tumor progression, metastasis, and chemoresistance. Thus, the promising potential of dsRNA analogues as a tumor therapeutic vaccine adjuvant should be evaluated cautiously.

Selection of Adjuvants for Enhanced Vaccine Potency

“…Foreign RNAs and RNA-like compounds can initiate immune stimulatory effects [380,381]. Such effects include activation of TLR3, recruitment of mature APCs, and induction of proinflammatory cytokines [381].…”

“…A synthetic and seemingly popular dsRNA is poly(I:C) (polyinosine-polycytidylic acid). The immune stimulatory effect of poly (I:C) is likely through activation of TLR3 [382,383], and possibly other receptors as well [380]. Stimulation of bone marrow-derived murine dendritic cell populations with poly(I:C) results in Th1-polarized maturation of dendritic cells in mice [92].…”

Induction of Broad-Based Immunity and Protective Efficacy by Self-amplifying mRNA Vaccines Encoding Influenza Virus Hemagglutinin

“…Thus, RNA replicon-based vaccines are amplified in the cells of the vaccinated hosts, permitting the expression of the vaccine antigen, without generating virus particles. Furthermore, in the process of amplification of their genomes, RNA replicons engage pattern recognition receptors in the host cell, adjuvanting the responses to the encoded immunogen (45)(46)(47). Although both mRNA-and replicon RNA-based vaccines were shown to elicit antigen-specific antibody and cellular immune responses against several pathogens (44,(48)(49)(50)(51), the self-amplifying nature of replicon-based vaccines is likely to result in higher levels of antigen expression and in a more effective engagement of innate immune responses than mRNA-based vaccine candidates.…”

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

“…* * P < 0.01, * * * P < 0.001. Jin et al, 2010). The imiquimod and resiquimod recognized by TLR7/8 are effective in activation of dendritic cells and B cells to elicit cytokines optimal for Th1 cell immunity, and antibody production.…”