GlaxoSmithKline Adjuvant Systems in vaccines: concepts, achievements and perspectives

Abstract

The need for potentiating immune responses to recombinant or subunit antigens has prompted GlaxoSmithKline (GSK) Biologicals to develop various Adjuvant Systems for the design of prophylactic and therapeutic vaccines. Adjuvant Systems are formulations of classical adjuvants mixed with immunomodulators, specifically adapted to the antigen and the target population. They can activate the appropriate innate immune system and subsequently impact on adaptive immune responses. AS04 is an Adjuvant System that has demonstrated significant achievements in several vaccines against viral diseases. AS02, another Adjuvant System, is being evaluated in various contexts, where a strong T-cell response is needed to afford protection. Likewise, AS01 has been developed for vaccines where the induction of a yet stronger T-cell-mediated immune response is required. Altogether, the promising clinical results strongly support the concept of Adjuvant Systems and allow for further development of new vaccines, best adapted to the target population and the immune mechanisms of protection.

Evaluation of the Safety and Immunogenicity of Two Antigen Concentrations of the Mtb72F/AS02ACandidate Tuberculosis Vaccine in Purified Protein Derivative-Negative Adults

“…All AEs reported were transient, and most resolved within 1 to 4 days. The pattern of AEs observed has previously been reported with other vaccines containing AS02 A (14,16,37,(40)(41)(42). No clinically significant changes in laboratory test (biochemistry and hematology) values related to vaccination were observed.…”

“…Physiological saline and AS02 A were manufactured at GSK Biologicals, Rixensart, Belgium. AS02 A is a proprietary oil-in-water emulsion with two immunostimulants, monophosphoryl lipid A (MPL) and Quillaja saponaria fraction 21 (QS21) (14). The vaccines were reconstituted by adding saline or AS02 A to the Mtb72F lyophilized pellet.…”

Potential adjuvantic properties of innate immune stimuli

“…MPL TM , also known as AS04, has recently been approved for use in Europe and is defined as 3-O-desacyl-4'-monophosphoryl lipid A, obtained by mild hydrolytic treatment and purification of Salmonella minnesota R595 LPS, and absorbed on aluminum hydroxide or aluminum phosphate. 46,47 The potent adjuvanticity and good safety profile of MPLA has spawned a large number of synthetic lipid A mimics including a new class of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates (AGPs) 48,49 such as Corixa's (now GlaxoSmithKline) Ribi 529, [50][51][52] and Eisai's E6020 (Fig. 2).…”

Mucosally-targeted HIV-1 vaccines

“…16 Although one of these agonists (MPL) has been included into a vaccine adjuvant licensed for use in man 17 in many respects these agents have so far been disappointing. For example, nucleic acidbased TLR ligands used alone have a short lifespan in vivo as a result of degradation and diffusion away from the site of antigen administration, and may induce unacceptably high levels of systemic inflammation or autoimmune reactivity.…”