Abstract
Vaccines are powerful tools for controlling microbial infections and preventing epidemic diseases. Efficient inactive, subunit, or viral-like particle vaccines usually rely on a safe and potent adjuvant to boost the immune response to the antigen. After a slow start, over the last decade there has been increased developments on adjuvants for human vaccines. The development of adjuvants has paralleled our increased understanding of the molecular mechanisms for the pattern recognition receptor (PRR)-mediated activation of immune responses. Toll-like receptors (TLRs) are a group of PRRs that recognize microbial pathogens to initiate a host’s response to infection. Activation of TLRs triggers potent and immediate innate immune responses, which leads to subsequent adaptive immune responses. Therefore, these TLRs are ideal targets for the development of effective adjuvants. To date, TLR agonists such as monophosphoryl lipid A (MPL) and CpG-1018 have been formulated in licensed vaccines for their adjuvant activity, and other TLR agonists are being developed for this purpose. The COVID-19 pandemic has also accelerated clinical research of vaccines containing TLR agonist-based adjuvants. In this paper, we reviewed the agonists for TLR activation and the molecular mechanisms associated with the adjuvants’ effects on TLR activation, emphasizing recent advances in the development of TLR agonist-based vaccine adjuvants for infectious diseases.
Highlights
Since they were first introduced more than 200 years ago, vaccines have been used as powerful tools to reduce the morbidity and mortality of infectious diseases
myeloid differentiation primary response 88 (MyD88) recruits IL-1R-related kinase 4 (IRAK4) and activates IRAK1 and IRAK2 to form a complex with tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), which promotes the association of transforming growth factor (TGF)-β-activated kinase 1 (TAK1) with TAK-binding protein (TAB)2 and TAB3
An intradermal injection these investigated in the hope that they could be developed as adjuvants for increasing the primates with Toll-like receptors (TLRs) agonists induced a rapid expansion of neutrophils and CD14+ monoefficacy of their vaccines
Summary
Since they were first introduced more than 200 years ago, vaccines have been used as powerful tools to reduce the morbidity and mortality of infectious diseases. The commercial production of squalene often uses squalene derived from shark livers [13,14,15,16] The development of these squalene-based adjuvants has allowed for the creation of effective vaccines against seasonal, avian, and pandemic influenzas. The squalene-based emulsions are superior to Freund’s adjuvant and aluminum salts in terms of their safety and adjuvant activities It uses an empirical approach by formulating compounds for increasing vaccine immunogenicity without a clear understanding of the underlying mechanisms. AS04, which contains a TLR4 agonist monophosphoryl lipid A (MPL), was first formulated as an adjuvant in the hepatitis B virus (HBV) vaccine and was used in the human papillomavirus (HPV) vaccine These AS04-adjuvanted vaccines were licensed in the early 2000s [26,27,28]. We comprehensively review the functional mechanisms of TLR agonist-based adjuvants and the recent progress in the development of TLR agonists as vaccine adjuvants for infectious diseases
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