TLR agonists as vaccine adjuvants in the prevention of viral infections: an overview

Abstract

Tol-like receptor (TLR) agonists, as potent adjuvants, have gained attention in vaccine research for their ability to enhance immune responses. This study focuses on their application in improving vaccine efficacy against key viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and flaviviruses, including West Nile virus, dengue virus, and chikungunya virus. Vaccines are crucial in preventing microbial infections, including viruses, and adjuvants play a vital role in modulating immune responses. However, there are still many diseases for which effective vaccines are lacking or have limited immune response, posing significant threats to human health. The use of TLR agonists as adjuvants in viral vaccine formulations holds promise in improving vaccine effectiveness. By tailoring adjuvants to specific pathogens, such as HBV, HCV, HIV, SARS-CoV-2, influenza virus, and flavivirus, protective immunity against chronic and emerging infectious disease can be elicited.

Unraveling the Complexities of Toll-like Receptors: From Molecular Mechanisms to Clinical Applications

“…For infectious diseases, TLR agonists have been formulated as licensed vaccines for their adjuvant activity, and other TLR agonists have been developed for this purpose [93]. Monophosphoryl lipid A and CpG-1018 have been used as adjuvants in vaccines against viral infections, including hepatitis B virus, hepatitis C virus, human immunodeficiency virus, SARS-CoV-2, influenza virus, and flaviviruses [94].…”

Recent Insights into the Molecular Mechanisms of the Toll-like Receptor Response to Influenza Virus Infection

“…In a Phase III clinical trial, HEPLISAV-B, a recombinant HBV vaccine composed of HBsAg combined with the CpG 1018 adjuvant, produced a highly sustainable seroprotective response with fewer immunizations, including in individuals with poor vaccine response, while maintaining a favorable profile [ 103 , 104 ]. TLR agonists are potent immunomodulators capable of inducing the production of IFN, proinflammatory cytokines, and chemokines, and they have been shown to be promising candidates against many viral infections, including IAV [ 105 , 106 ].…”

Modulation of the Adjuvant Potential of Imidazoquinoline-Based TLR7/8 Agonists via Alum Adsorption

“…7,8 These comprise oil emulsions, toll-like receptor (TLR) agonists, and polysaccharide particles or a combination of these. 9,10 TLRs recognize unique chemical structures called pathogenassociated molecular patterns (PAMPs). 11−13 In humans, TLR7 is expressed by plasmacytoid dendritic cells (pDCs) and B cells, whereas TLR8 is expressed by monocytes and myeloid dendritic cells (mDCs).…”

“…When used without Scheme 1. Synthesis of m-AM-BBIQ (10) alum, 10 and 11 showed some adjuvant action, with the induction of IgG2c but not IgG1, characteristic of a Th1 immune response (Figure 1). IgG1 was only induced when 10 or 11 was coformulated with alum, although not to higher levels The antibody response to HBs (Figure 1, bottom panel) was different from the Sp antibody responses in the same animals with an IgG1 and IgG2b/c response against HBs.…”

“…The role of an adjuvant is to generate a robust and durable protective immune response against a coadministered antigen. , Adjuvants work in various ways, including by creation of an antigen depot, enhanced delivery of antigen to antigen-presenting cells (APCs), and/or induction of chemokines and cytokines that help enhance the activation of T and B cells. , Aluminum hydroxide (alum) is currently used in more than 25 FDA-licensed vaccines. Other adjuvants included in licensed vaccines include MF59, AS01, AS03, CpG, and Advax-CpG55.2. , These comprise oil emulsions, toll-like receptor (TLR) agonists, and polysaccharide particles or a combination of these. , …”