lipid-a and Virus-Diseases

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.

Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Aluminum Hydroxide; Animals; Drug Combinations; Drug Industry; Humans; Lipid A; Malaria; Saponins; Vaccines; Virus Diseases

Toll-like receptor (TLR) agonists are being developed for use as vaccine adjuvants and as stand-alone immunomodulators because of their ability to stimulate innate and adaptive immune responses. Among the most thoroughly studied TLR agonists are the lipid A molecules that target the TLR4 complex. One promising candidate, monophosphoryl lipid A, which is a derivative of lipid A from Salmonella minnesota, has proven to be safe and effective as a vaccine adjuvant in > 120,000 human doses. A new class of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates (AGPs), have been engineered specifically to target human TLR4 and are showing promise as vaccine adjuvants and as monotherapeutic agents capable of eliciting nonspecific protection against a wide range of infectious pathogens. In this review, the authors provide an update of the preclinical and clinical experiences with the TLR4 agonists, MPL (Corixa Corporation) adjuvant and the AGPs.

Topics: Adjuvants, Immunologic; Aged; Animals; Antiviral Agents; Bacterial Infections; Bacterial Vaccines; Child; Clinical Trials as Topic; Drug Design; Drug Evaluation, Preclinical; Female; Glycolipids; Humans; Immunologic Factors; Lipid A; Lymphocyte Activation; Male; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Molecular Structure; Protozoan Infections; Receptors, Cell Surface; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Toll-Like Receptor 4; Toll-Like Receptors; Viral Vaccines; Virus Diseases; Virus Replication