Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 567

11.5.8 Vaccines Adjuvants
Vaccines remain a key tool in the defense against major diseases. In the development
of vaccines, safety and efficacy are required. Adjuvants are employed to improve
vaccines' potency, but currently there are only a limited number of adjuvant systems,
like aluminum, which are licensed for clinical use. Of the new adjuvants being inves-
tigated (shown in Fig. 11.11 ), particulate systems, which induce both cellular and
humoral immune response, offer several advantages, including passive targeting to
the antigen-presenting cells within the immune system, protection against adjuvant
degradation, thermal stability [345] , antigenicity by adjuvant action, stabilization of
antigen, and ability for modified and sustained antigen release.
Development of a pulsatile release pattern may also allow a single injection to
provide both the primary and booster immunizations [137] . A range of particulate
peptide, protein antigens, and DNA vaccine delivery systems are outlined in recent
patents, including polymer-based microspheres, nanoparticles (which are generally
more focused on the use of synthetic polymers, in particular polyesters), and surfac-
tant-based vesicles. Within these formulations, cationic liposome and mannosylated
liposomes have clearly shown strong potential as adjuvants [346] .
The interaction of the particulate system with macrophages depends upon the particle
size [347,348] . After administration in vivo , particles are ingested by antigen-presenting
cells, where the immunogenic material is released for processing and presentation on
the cell surface, which actually initiates the adaptive immune response. The nonphago-
cytosed or nonendocytosed fraction of particles remain at the site of administration,
where they release immunogenic material in a sustained or pulsatile fashion, providing
long-term antigen supply to the immune system for prolonged effects [349] .
The most extensively studied polymers for encapsulating vaccine antigens are
PLGA [348] , triblock (ABA) copolymers of PLGA and PEO, and chitosan. Use of
a more hydrophilic acid-degradable crosslinker leads to increased water dispersibility
and increased protein loading efficiency for the particles, and shows effective cytotoxic
Figure 11.11 Particulate delivery systems and immunostimulants as vaccine adjuvant.