Microparticle Adjuvant

Novel vaccine adjuvant for cellular immunity

There is a great need for the development of vaccine adjuvants that promote the maturation of potent, long-lived, adaptive T cell immunity. In particular, new adjuvants are required that promote protective cellular Th1 responses for use in vaccines against intracellular pathogens and tumors where humoral immunity is ineffective. The development of effective therapeutic vaccines for patients with cancer or acquired chronic infections is further compounded by the failure of chronically infected or immunosuppressed patients to respond adequately to the vaccine adjuvant component. It is accepted that many novel vaccine designs fail due to the lack of an appropriate adjuvant that supports the development of sufficient cellular immunity. Classical antigen presenting cells, such as myeloid dendritic cells have long been considered the primary targets for vaccination. The induction of a potent cellular Th1 response however is now known to also require a simultaneous and co-ordinated response from key innate accessory cells such as plasmocytoid dendritic cells (pDC), natural killer T (NKT) cells and natural killer (NK) cells.

Schematic of immunomodulator microparticle adjuvant platform

incorporating select ligands (NOD-2 and TLR in this configuration) plus
covalently attached immunogen (in red).
A wide range of antigens / immunogens can be covalently attached to the microparticle
at up to 20 x the loading density displayed.

Microparticles area novel, second generation vaccine adjuvant and immunogen co-delivery system

Extensive in vitro and in vivo data have establishedkey adjuvant characteristics.

1. Targeted delivery of adjuvant with covalently attached immunogens to antigen presenting cells:
   • Readily taken up by plasmocytoid and myeloid dendritic cells, monocytes, and dendritic cells.
   • Induction of generalised proinflammatory response and induction of myeloid and plasmocytoid dendritic cell maturation.
   • Direct immunoinduction of pDC and NK associated cytokines which are important for the generation of polyfunctional adaptive Th1 responses.
   • Predictable and quantifiable attachment of protein and glycoprotein immunogens.
   • Capacity to attach other known immunomodulators and nucleic acid based therapeutics, such as RNAi, using biocompatible linkage technology.
2. Induction of effective humoral and cellular adaptive immune responses towards a broad range of immunogens in animal vaccination models:
   • Induction of rapid complete prophylactic immunity in an Anthrax lethal toxin challenge model.
   • Induction of cellular Th1 immunity in prophylactic and therapeutic tumour challenge models.
   • High titer neutralising antibodies to HIV, SARS, Anthrax toxins, and West Nile Virus antigens have been produced.
3. Non toxic and non immunogenic
• The microparticle adjuvant can comprise multiple immune agonist ligands that are preferentially reactive with cytosolic receptors. The lack of cell surface immunostimulatory activity prevents the formation of granulomatous inflammation and associated lesions.
• Cross linking agonist ligands into a microparticle structure achieves depot formation with resultant phagocytic cell uptake post administration and prevents systemic distribution with associated toxicities.

Informational Links:

MIS416, a non-toxic microparticle adjuvant derived from Propionibacterium acnes comprising immunostimulatory muramyl dipeptide and bacterial DNA promotes cross-priming and Th1 immunity, Vaccine. 2011 Jan 10;29(3):545-57.

The Therapeutic Vaccine Potential of MIS416 Adjuvant, from BioPharm International, 2009