Polyionic vaccine adjuvants: another look at aluminum salts and polyelectrolytes

Abstract

Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns [PAMPs] and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use.

Establishment of specific cytotoxic T lymphocyte culture system and its inhibitory effect on ovarian cancer

“…In the process of an immune response, tumor antigens are processed by APCs and presented to CTLs (14). Adjuvants are able to non-specifically alter or enhance the body's immune response to specific antigens, and enhance the immunogenicity of the corresponding antigen or change the type of immune response (37).…”

Immunological effects of adjuvants, their mechanisms, and relevance to vaccine safety

“…A few years later, British scientist Alexander Glenny discovered the immune-enhancing effects of aluminium salts (8). Aluminium was first used in human vaccines in 1932 and remained the only adjuvant in use in licensed human vaccines for approximately 70 years.…”

“…Mod ern human vaccines use pre-formed aluminium gels containing sulfate, phosphate or hydroxide salts of aluminum, but composition and higher order structure of different formulations varies considerably (8,22). For some proprietary aluminum salt adjuvants, the full chemical formula and process of formulation are not publicly available.…”

“…Practical goals of using adjuvants include: increasing the functional titer of antibodies raised against the target antigen; decreasing the dose of antigen needed to elicit immune reaction (antigen sparing); decreasing the number of doses needed to achieve complete immunization (dose reduction); enhancing immune responses in the young, elderly and immunocompromised populations (poor responders); increasing the duration of the vaccine-specific protective response; decreasing the time needed to achieve protective immunity; induction of potent cell-mediated immunity; balancing or redirecting the immune response toward the Th1, Th2, or Th17 arm of the T cell response, as required; inducing mucosal immunity; and inducing a broader immune response (cross-protection against related strains of pathogen not included in the vaccine) (7,8). In addition to achieving quantitative and qualitative alterations of the immune response, some of these goals, like antigen sparing and dose reduction, have important implications for improving global vaccine supply.…”

Dendritic cell-based vaccines in treating recurrent herpes labialis: Results of pilot clinical study

“…This water-soluble cationic polymer, which hasbeen specifically designed as vaccine adjuvant 27 activates anti-inflammatory signaling pathways and enhances antigen presentation and effector cell maturation. 28,29 Cells were then washed, harvested, aliquoted at concentration of 5 £ 10 6 DCs/ml, frozen in phosphate buffer solution/10% DMSO (Sigma Aldrich, Cat N 276855) and stored in a freezer (Sanyo Ultra Low) at ¡80 C until use. The purity of DCs was assessed by flow cytometry analysis (FACSCalibur; Becton Dickinson) using anti-HLA-DR, anti-CD86 and lineage (anti-CD3C, anti-CD20C, anti-CD56C) monoclonal antibodies (Becton Dickinson).…”