Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases

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.

Pairing Nanoparticles Geometry with TLR Agonists to Modulate Immune Responses for Vaccine Development

“…To explore this notion, TLR agonists, CpG, and imidazoquinoline derivatives were selected for our studies because they have a venerable history as vaccine adjuvants. , CpGs are synthetic oligodeoxynucleotides that trigger toll-like receptor 9 and activate innate immune responses by producing Th1-associated cytokines. , Although imidazoquinoline derivatives were identified as TLR 7/8 agonists, they induce pro-inflammatory cytokines such as TNF alpha and IL-12 . Both CpGs and imidazoquinoline have been extensively used as adjuvants in several vaccines. − However, to the best of our knowledge, they have never been studied together on a nanotechnology platform.…”

Comparative Study of Immunoglobulin G and Gender between COVID-19 Patients and Vaccinated Iraqi Individuals with Pfizer, AstraZeneca and Sinopharm Vaccine

“…Also enhancing the immune system's cellular and humoral responses. Additionally vectors vaccine have the ability to act like adjuvants, activating the immune system through both TLR-dependent and TLR-independent routes (16) .…”

How Can We Improve Vaccination Response in Old People? Part I: Targeting Immunosenescence of Innate Immunity Cells

“…Different TLR agonists are currently used in licensed vaccines as adjuvants and others are being developed for this purpose. The TLR4 agonist 3-O-desacyl-40 -monophosphoryl lipid A (MPL), a detoxified derivative of LPS extracted from Salmonella minnesota, is a part of AS01 adjuvant system, containing liposomes and the saponin QS-21, extracted from Quillaja saponaria Molina [ 118 ]. The AS01 adjuvant system was first formulated for malaria vaccination and then for a recombinant varicella zoster vaccine.…”

“…MPL is also part of the AS04 adjuvant system, in combination with aluminium salts, formulated as an adjuvant for vaccination against hepatitis B (licensed in 2005), and was then used in a human papillomavirus vaccine (licensed in 2007). In both vaccines, AS04 has induced a greater uptake of antigens by APCs and higher levels of antibodies than the same vaccine with just alum as the adjuvant [ 118 ]. The presence of alum in the AS04 formulation seems to prolong the MPL-mediated cytokine response by DCs [ 120 ].…”