Adjuvant system AS01: helping to overcome the challenges of modern vaccines

Abstract

Introduction: Adjuvants are used to improve vaccine immunogenicity and efficacy by enhancing antigen presentation to antigen-specific immune cells with the aim to confer long-term protection against targeted pathogens. Adjuvants have been used in vaccines for more than 90 years. Combinations of immunostimulatory molecules, such as in the Adjuvant System AS01, have opened the way to the development of new or improved vaccines. Areas covered: AS01 is a liposome-based vaccine adjuvant system containing two immunostimulants: 3-O-desacyl-4ʹ-monophosphoryl lipid A (MPL) and the saponin QS-21. Here we describe studies investigating the mode of action of AS01, and consider the role of AS01 in enhancing specific immune responses to the antigen for selected candidate vaccines targeting malaria and herpes zoster. The effects of AS01 are rapid and transient, being localized to the injected muscle and draining lymph node. AS01 is efficient at promoting CD4 + T cell-mediated immune responses and is an appropriate candidate adjuvant for inclusion in vaccines targeting viruses or intracellular pathogens. Expert commentary: AS01 activity to enhance adaptive responses depends on synergistic activities of QS-21 and MPL. AS01 adjuvantation shows good prospects for use in new vaccines targeted to populations with challenging immune statuses and against diseases caused by complex pathogens. ARTICLE HISTORY

Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development

“…Adjuvant system (AS) 01 and 04 used the combination of an immunomodulatory molecule and a particulate formulation composed of a Toll-like receptor 4 (TLR4) agonist, monophosphoryl lipid A that also induces Ab. The incorporation of alum in AS04 improved the humoral response, while the association of saponin (QS-21) and liposome in AS01 favored Th1 responses (3, 4). Imidazoquinolines (TLR7 and TLR8 agonists) and lipid A analogs (TLR4 agonists) are immunomodulatory molecules, capable of generating a Th1 response (5).…”

Adjuvant formulations for virus-like particle (VLP) based vaccines

“…AS01/AS02 have very broad immunomodulatory activity. MPL stimulates TLR4 with the subsequent induction of a Th1-mediated response and antibody production (see above), QS21 promotes antibody generation and CD8+ T cell activation, and the liposomes or emulsion stimulate antigen uptake from the APC such as dendritic cells [76,77]. The VLP-based vaccine against malaria RTS,S (Mosquirix, GSK) has shown a better immune response and improved efficacy in several clinical trials when formulated with AS01 in comparison with AS02 [78,79].…”

Modulating the immune system through nanotechnology

“…In 2015, GSK licensed a vaccine under the name of Mosquirix™, that contains the circumsporozoite protein of Plasmodium falciparum and the liposome-based adjuvant AS01, composed by monophosphoryl lipid A (MPLA) and the saponin QS-21 [176]. This new vaccine has shown good safety profiles and an efficacy rate of 50 % [177], leaving the door open for new improved systems.…”