An adjuvant is a chemical or an ingredient used in a vaccine to enhance the production of antibodies. Adjuvants are broadly separated into two classes, based on their principal mechanisms of action; vaccine delivery systems and adjuvants that stimulate the immune response. Vaccine delivery systems are generally particulate e.g. emulsions, microparticles, iscoms and liposomes, and target the antigen presenting cells (APC). In contrast, 'adjuvants that stimulate the immune system are predominantly derived from pathogens (viruses and bacterial cell walls). The particles, e.g. LPS, MPL, CpG DNA, activate cells that are part of the innate immune system.
March 30, 2020 - Inflammasomes as Targets for Adjuvants "Inflammasomes are expressed in various cells, including granulocytes, Т- and В-cells, monocytes, hepatocytes, neurons, microglia, and Langerhans cells. The functions of inflammasomes include sensing the pathogen and launching a subsequent innate immune response. Inflammasomes are formed when PAMP and DAMP are sensed in the cytoplasm . This induces conformational changes in the pre-assembled NLRP3-inactive inflammasome. Finally, activated inflammasome proteolytically cleaves pro-caspase 1, releasing the active caspase 1. Next, the caspase-1 digests pro-interleukin-1-beta (IL-1β) and pro-interleukin-18 (IL-18) to their active forms, which are secreted by a cell. These interleukins are involved in establishing the inflammation and immune response that protect against microorganisms.
December 22, 2016 – The Impact of the Gut Microbiota on Humoral Immunity to Pathogens and Vaccination in Early Infancy (full text) ” Given the dynamic nature of the infant gut microbiota and the importance of robust humoral immunity to protection against life-threatening pathogens, future pediatric vaccine research should evaluate the manipulation of the infant microbiome to modulate desirable immune responses. Not only are the developing immune systems of infants distinct from those in adults, but the composition and influence of the gut microbiome on infant immune system is also unique. Therefore, the infant microbiome should be explored 'as potential source of immune response modulation and enhancement of vaccine efficacy.”
March 7, 2016 – A Method for Producing Protein Nanoparticles with Applications in Vaccines (full text) “Examples presented include single-component particles of the malarial antigens AMA1, CSP and Pfs25, and two component particles comprised of those antigens covalently cross-linked with the immunogenic carrier protein EPA (a detoxified form of exotoxin A from Pseudomonas aeruginosa).”…”The examples include particles comprised of the antigens alone or the antigens combined with the immunogenic carrier protein EPA. Although the proteins were structurally quite different, they each performed similarly in forming particles, indicating that the described method may have general utility for preparing protein nanoparticles from soluble proteins.”…”The efficacy of the Pf25-EPA product vaccine is currently being evaluated in clinical trials and has passed safety evaluations (clinicaltrials.
October 13, 2015 – Recent advances in the molecular design of synthetic vaccines “Vaccines have typically been prepared using whole organisms. These are normally either attenuated bacteria or viruses that are live but have been altered to reduce their virulence, or pathogens that have been inactivated and effectively killed through exposure to heat or formaldehyde. However, using whole organisms to elicit an immune response introduces the potential for infections arising from a reversion to a virulent form in live pathogens, unproductive reactions to vaccine components or batch-to-batch variability.”
November 2011 – Immunomodulatory properties of vitamins, flavonoids and plant oils and their potential as vaccine adjuvants and delivery systems.
October 2011 – Innate immunity and adjuvants. (full text)
September 2011 – New developments in vaccine research — unveiling the secret of vaccine adjuvants.
August 23, 2011 – Current status of multiple antigen-presenting peptide vaccine systems: Application of organic and inorganic nanoparticles (full text)
June 24, 2011 – NIAID Strategic Plan for Research on Vaccine Adjuvants—Introduction “Vaccines made from inactivated or live-attenuated pathogens generally contain naturally occurring molecules such as PAMPs that act as adjuvants. In contrast, vaccines made from recombinant proteins or purified subunits of a pathogen are often poorly immunogenic because they lack the endogenous innate immunostimulatory components of the pathogen and, therefore, may necessitate the addition of an adjuvant to elicit an effective immune response. Some polysaccharide conjugate vaccines, such as Prevnar-7 and -13, are formulated with alum as an adjuvant; although others are effective in the absence of any known adjuvant; it is not yet known whether the latter vaccines engage innate immune pathways.”
June 7, 2011 – Modulation of soluble and particulate antigen transport in afferent lymph by monophosphoryl lipid A
April 2011 – Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems.
January 2011 – Highly effective generic adjuvant systems for orphan or poverty-related vaccines.
June 2010 – Adjuvants for cancer vaccines.
May 27, 2010 – Mycobacterial Lipids for Use in Vaccine Delivery Liposomes with an Adjuvant Effect
2010 – Synthetic and natural TLR4 agonists as safe and effective vaccine adjuvants.
October 2009 – Virus-like particle vaccines and adjuvants: the HPV paradigm.
April 10, 2009 – Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques (full text)
January 1, 2009 – A Simple Mycobacterial Monomycolated Glycerol Lipid Has Potent Immunostimulatory Activity1 (full text)
August 1, 2006 – Innate Inflammatory Signals Induced by Various Pathogens Differentially Dictate the IFN-I Dependence of CD8 T Cells for Clonal Expansion and Memory Formation (full text)
September 2005 – Cationic Liposomes Containing Mycobacterial Lipids: a New Powerful Th1 Adjuvant System (full text) “The immunostimulation provided by the mycobacterial cell wall has been exploited for many decades, e.g., in Freund’s complete adjuvant. Recently, the underlying mechanism behind this adjuvant activity, including Toll receptor signaling, has begun to be unraveled, confirming the potential of mycobacterial constituents to act as adjuvants.”
December 2004 – Inulin-derived adjuvants efficiently promote both Th1 and Th2 immune responses (full text) “A major problem in the search for the ideal adjuvant is that adjuvants that promote cell-mediated (Th1) immunity (e.g. Freund’s complete adjuvant) generally have unacceptable local or systemic toxicity that precludes their use in human vaccines. There is a need for a safe, non-toxic adjuvant that is able to stimulate both cell-mediated and humoral immunity. Inulin-derived adjuvants that principally stimulate the innate immune system through their ability to activate the alternative complement pathway have proven ability to induce both cellular and humoral immunity.”
December 2004 – Novel adjuvant based on a proteoliposome-derived cochleate structure containing native lipopolysaccharide as a pathogen-associated molecular pattern (full text) “Recently, there has been an increasing emphasis on the development of novel adjuvant immunopotentiator and delivery systems to improve efficacy of vaccine formulations. CS have a good delivery capacity and high stability, but no successful adjuvant applications for these structures have been reported. Nonetheless, CS obtained from an artificial mix of commercial lipids have been used for drug delivery with promising results. In the present work, we obtained CS of natural components from the outer membrane of N. meningitidis B, which constitute a source not only of phospholipids, but also of proteins and other PAMP that strongly activate the immune system.”
December 2004 – Shaping of adaptive immune responses to soluble proteins by TLR agonists: A role for IFN-alpha/bold beta (full text)
December 2004 – Mucosal adjuvants and delivery systems for protein-, DNA- and RNA-based vaccines (full text)
December 2004 – Adjuvant synergy: The effects of nasal coadministration of adjuvants (full text)
1993 – Adjuvants — a balance between toxicity and adjuvanticity
April 1986 – Early-Phase Endotoxin Tolerance: Induction by a Detoxified Lipid A Derivative, Monophosphoryl Lipid A (pdf) “The major obstacle which has limited the clinical application of endotoxin for its beneficial effects has been its toxic side effects. Chemical modification of the endotoxin molecule has resulted in a nontoxic, MPL which, because of its greatly reduced capacity to cause endotoxicity, holds great potential for clinical utilization.”